WHE guide by New Media B2B

WHE

Women’s Health Essentials

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At Cipla, we deeply value the vital role women play in families, workplaces, and society.

As Michelle Obama aptly stated, ‘communities and countries… are only as strong as the health of their women’. Despite their importance, gender disparities in healthcare persist globally. Women face unique health challenges, from menstrual and maternal health to a higher risk of conditions like certain cancers.

Cipla is committed to more than manufacturing medicine. We strive to improve lives by ensuring equitable access to quality, life-saving medication and prioritising health education. Empowering individuals

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with knowledge enables them to make informed decisions about their health and well-being.

This booklet focuses on key women’s health issues, including reproductive health, mental health, and overall wellness. It is designed to provide valuable insights for healthcare practitioners and, most importantly, their patients.

Warmest regards

Paul Miller

CEO: Cipla South Africa www.cipla.co.za

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The power of the pill

Contraception plays a vital role in reproductive health worldwide, with millions of women relying on various methods to prevent pregnancy. Among these, oral contraceptives (OCs) stand out not only for their contraceptive efficacy but also for their extended health benefits.

Migraine prevention is another benefit associated with the use of COCs, particularly in alleviating premenstrual migraines triggered by fluctuations in oestrogen levels.7,8

Continuous use of combined OCs (COCs) has been associated with a reduction in dysmenorrhea recurrence, pelvic pain, and endometrioma recurrence.1,3

Shown to reduce the risk of pelvic inflammatory disease by 50%-70%, leading to fewer hospitalisations, less medication and surgeries, and lower risks of ectopic pregnancy and infertility, with less severe inflammation during pill intake.6

OC use is linked to a reduced risk of endometrial, ovarian, and colorectal cancers, possibly due to the suppression of ovulation and gonadotropin hormone secretion.

Suppress the hypothalamicpituitary-ovarian axis, protecting against follicular and corpus luteum cysts, depending on the contraceptive type used.6

Reduce sebum production a key driver in acne onset. Additionally, the interaction between oestrogen and progestogens in these pills aids in addressing acne by increasing sex hormone-binding globulin and modulating androgen receptors.4

By addressing menstrual irregularities, acne, and hirsutism, OCs provide comprehensive management for polycystic ovary syndrome symptoms.5

In peri-menopausal women, COCs can help regulate irregular cycles, reduce bleeding and pain, and alleviate vasomotor symptoms, thus improving overall quality of life during this transitional phase.4

COCs with specific compositions have been shown to alleviate the physical and emotional symptoms of pre-menstrual dysmorphic disorder.3

COCs could prevent the initiation or extension of endometriosis by two mechanisms: the volume of menstrual flow is reduced and progestogens, either directly or by their anti-estrogenic effect, prevent implantation and growth of endometrial cells.4

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Selecting the right contraceptive for the right patient

Contraception needs vary greatly over a woman’s reproductive lifespan, influenced by age, life circumstances, and preferences for different methods’ characteristics, highlighting that a ‘one size fits all’ approach is ineffective. When selecting the most suitable contraceptive option, it is essential to consider individual patient values and preferences.1,2

Globally, the six most common contraceptive methods are:3

_ 24% – Female sterilisation

_ 21% – Male condom

_ 17% – Intrauterine devices (IUD)

_ 16% – Oral contraceptive pill

_ 10% – Injections and implants

_ 9% – Traditional methods (withdrawal, calendar method and other traditional methods).

In southern sub-Saharan Africa, the top seven contraceptive methods are:4

_ 40.8% – Injections

_ 21.4% – Condoms

_ 18.7% – Oral contraceptive pills

_ 8.5% – Implants

_ 6.7% – Female sterilisation

_ 1.4% – IUDs

_ 0.5% – Male sterilisation.

Research indicates that contraception preference varies depending on a woman’s age and relationship status. For instance, adolescents aged 15- to 19- years tend to opt for short-term methods, such as oral contraceptives and condoms. In contrast, adult women aged 20- to 49-years often prefer long-acting reversible contraceptives (LARCs).4

Additionally, studies reveal that female sterilisation is more prevalent among older age groups compared to younger ones and partnered women are more likely to use IUDs, whereas unpartnered women commonly rely on oral contraceptives and condoms. 4

Reversible contraception

Reversible contraceptives are broadly categorised into:2

Hormonal contraception

Hormonal contraceptives include progestins and oestrogens, with most formulations combining a progestin with ethinylestradiol, a synthetic oestrogen. Progestins,

synthesised from testosterone, exert their contraceptive effects primarily by suppressing ovulation and altering cervical mucus permeability. Progestins, also reduce endometrial receptivity and sperm transport to the fallopian tube. 2

Oestrogens, particularly ethinylestradiol in combined hormonal contraceptives, contribute to contraceptive efficacy by suppressing gonadotropins and folliclestimulating hormone, thereby preventing the development of a dominant follicle and reducing irregular bleeding. 2

Progestin-only contraceptives offer diverse options, including pills, injectables, and LARCs such as the levonorgestrel (LNG) IUD and subdermal implant.

Progestin-only pills vary in their ability to suppress ovulation, with formulations like norethindrone and drospirenone differing in dose and potency. 2

Depot medroxyprogesterone acetate injections provide long-lasting contraception with potential for amenorrhea, making it suitable for certain patient populations.

Progestin-only long-acting methods boast efficacy rates similar to permanent contraception methods and allow rapid return to fertility upon discontinuation. 2

Combined hormonal contraceptives, comprising oestrogen and progestin, include OCs, vaginal rings, and transdermal patches. While offering comparable efficacy to progestin-only methods, combined hormonal contraceptives provide the advantage of producing regular bleeding patterns. 2

They prevent pregnancy through mechanisms similar to progestin-only methods, with added benefits of improved cycle control. However, their use is associated with risks, particularly venous thromboembolism mediated by oestrogen exposure. Despite this, combined hormonal contraceptives remain a popular choice for many individuals due to their efficacy and convenience. 2

Clinicians prescribing hormonal contraceptives must consider individual patient factors, including risk profiles and preferences, to guide appropriate selection. Patients at increased risk of thrombotic events, such as those with obesity, smoking history, or hypertension, may be advised against combined hormonal contraceptives. 2

In such cases, progestin-only methods offer a safer alternative, as they do not increase the risk of venous thromboembolism. Patient counselling regarding signs and symptoms of arterial and venous thrombosis is essential, especially for those with additional risk factors. 2

Non-hormonal contraception

Non-hormonal contraceptive methods offer alternative

options for individuals seeking effective pregnancy prevention without the use of hormonal agents. These methods include behavioural strategies, barrier methods, the copper-bearing IUD, emergency contraception (EC), and oral EC. Each method comes with its own set of considerations regarding efficacy, mechanism of action, and practicality. 2

Behavioural contraceptive methods rely on patient education and awareness of fertility signs. These methods, such as penile withdrawal and fertility awareness-based methods, require diligent monitoring of symptoms like cervical mucus consistency and basal body temperature. 2

However, their effectiveness can vary widely depending on patient commitment and cycle regularity, with fertility awareness methods exhibiting failure rates of 22 pregnancies per 100 women-years in higher-quality prospective studies. 2

Barrier methods, including condoms, diaphragms, spermicides, and pH modulators, physically prevent sperm from entering the upper reproductive tract. These methods offer first-year typical use effectiveness rates of 13 pregnancies per 100 women, providing moderate protection against unintended pregnancies. 2

The copper-bearing IUD represents a highly effective non-hormonal reversible contraceptive option, with typical use pregnancy rates of only 1% per year. Its mechanism of action involves spermicidal effects mediated by copper salts and inflammatory changes in the endometrium. 2

While the copper IUD does not affect ovulation or menstrual cyclicity, it may increase menstrual flow and discomfort, particularly during the initial months of use. 2

Both the copper IUD and oral EC offer effective options for reducing pregnancy risk following unprotected intercourse. The copper IUD, when placed within five days of unprotected intercourse, can reduce pregnancy risk to 0.1% and provides ongoing contraception thereafter. 2

Oral EC, consisting of a single dose of either a progestin or anti-progestin, works by blocking or delaying ovulation and is available over-the-counter or by prescription. Ulipristal acetate EC can be taken up to five days after intercourse, while LNG EC efficacy diminishes after three days.2

Clinicians prescribing oral EC should counsel patients on the importance of timely administration for maximum efficacy. Additionally, patients starting user-controlled methods like condoms may be provided with oral EC to keep at home for immediate use if needed, with repeat dosing recommended in cases of further unprotected intercourse within 24 hours. 2

Scan the QR code on page 3 for reference lists. SF

Contraception for savvy young women

Dr Ilhaam Mohamed, medical writer

In adolescents, oral contraception is an option in preventing unwanted pregnancy. In South Africa, the number of estimated pregnancies in young teenagers aged 10 to 14 years and adolescents aged 15 to 19 increased between 2017 and 2021.1,2

Adolescents often have an irregular lifestyle and difficulties in assessing the risk of unintended pregnancy. Those who are <21 years of have a risk of unintended pregnancy almost twice as high as the risk among older women. Furthermore, they may be even more susceptible to contraceptive failure due to missed pills and poor adherence compared to older women. 3

Bleeding irregularities and side effects associated with the use of combined oral contraceptives (COCs), are some of the major reasons for discontinuation of oral contraceptives.3,4

Compared to the first COC with high doses of oestrogen and progesterone, and to reduce health risks and negative effects associated with COCs, new administration regimes and changes in dosage have been developed over the years.1

Mechanism of action

Oestrogen contributes to the anti-ovulatory mechanism of COCs by suppressing both follicle – stimulating hormones and luteinising hormone (LH). It also helps in stabilising the endometrium, thus providing better cycle control. 6

Gestodene, a third-generation progestin, is a derivative of 19- nortestosterone. It is without significant residual androgenic effects but has slight mineralocorticoid activity and excellent anti-oestrogen activity. With a high affinity for sex-hormone binding globulin, gestodene has a lower metabolic clearance rate and a greater concentration in the circulation. This aspect may be particularly beneficial in case of missed pills.1,6

Gestodene works by preventing ovulation, mediated by negative feedback on the hypothalamic-pituitary-ovarian axis resulting in a decrease in LH. It also reduces cervical mucus receptivity of the sperm and endometrial thickness. 6

Formulation benefits

A COC with gestodene 0.06mg and ethinylestradiol

(EE) 0.015mg offers the lowest hormonal dose in a 24/4 treatment regimen. The use of lower hormonal doses in COCs has the potential to reduce common side effects associated with oral contraceptive use, such as nausea and breast tenderness. In studies, the gestodene/EE low dose 24/4 regimen was associated with a lower incidence of oestrogen-related adverse events, such as headache, breast tenderness, and nausea. 6

As the treatment cycles progress, the incidence of breakthrough bleeding is reduced. As a 24/4 regimen, this reduction in the hormone-free interval reduces the risk of escape ovulation, preventing contraceptive failure. Clinically, compared with the 21/7 regimen, shortening the HFI with a 24/4 regimen may increase the contraceptive safety margin when pills are omitted or missed. 6

COCs containing a low dose of oestrogen have not been associated with adverse effects on haemostasis in healthy women. The contraceptive efficacy of COCs with 0.015mg and 0.02mg EE, measured by the Pearl index, is in the range of 0.07-0.88, and is therefore similar to that of COCs containing 0.03mg EE (0.06-0.88).1,6

Conclusion

When choosing a COC regimen for a woman, it is recommended to select one with lowest dose of oestrogen and progestogen to provide good cycle control and effective contraception.

Gestodene/EE is an oral contraception, indicated for the prevention of pregnancy. It is an ultra-low dose COC formulation, which combines two hormones: a progestin component and an oestrogen component. This formulation may be best suited to young, recently sexually active women preferring stable cycles with lighter, shorter withdrawal bleeds.

Scan the QR code on page 3 for reference lists. SF

A ﬁ rst-choice gestodenecontaining COC* (combined oral contraceptive) for women through to menopause1,2,3

A ﬁ rst choice gestodenecontaining COC* for young women1A,2A+B

PATIENT PROFILE

• Healthy, non-smoking 35-year-old woman - Lerato**

• On a very low dose COC* (20 µg ethinylestradiol) but experiencing breakthrough bleeding in the ﬁrst half of her cycle

• Wants a COC* that will improve cycle control and can be used continuously up to menopause

BENEFITS OF CARMADENE

• Higher ethinylestradiol improves breakthrough bleeding in the ﬁ rst half of the cycle1,4

• Better cycle control vs. 15 µg desogestrel / 20 µg ethinylestradiol3

A ﬁ rst-choice gestodenecontaining COC* for younger girls & teenagers with stable cycle control1A

PATIENT PROFILE

• Healthy, 25-year old woman

• Suﬀers from primary dysmenorrhoea and premenstrual symptoms

• Wants good cycle control and the option to delay a period when necessary

• Seeking contraception without weight gain

BENEFITS OF ACTORDENE

• A good ﬁrst choice COC* for young, healthy women1A+B

• Shown to eﬀectively reduce primary dysmenorrhoea and premenstrual symptoms3,4A

• Provides good cycle control4A

PATIENT PROFILE

• 17-year-old girl, recently became sexually active

• Heavy, painful periods

• Suﬀering from premenstrual syndrome

BENEFITS OF NESSIFEM

• Maintains cycle control with a lighter & shorter withdrawal bleed4A

• Eﬀective ovulation inhibition & contraception 3A+B

• Improves premenstrual syndrome symptoms4A

• Gestodene is androgenically neutral leading to fewer androgenic side eﬀects1C

• Suitable for healthy, non-smoking women up to menopause3

• Gestodene is androgenically neutral1

• Gestodene is androgenically neutral2D with negligible changes in body weight4B

• Can be used to delay a period

Cycle SOS: Decoding AUB and dysmenorrhoea

AUB is an umbrella term for heavy, irregular, and intermenstrual bleeding, along with deviations in cycle length – either more frequent or less frequent than the typical range of 24 to 38 days.1

Most adolescents experience primary dysmenorrhoea, defined as painful menstruation without pelvic pathology. This typically begins when adolescents start having ovulatory cycles, usually within six to 12 months of menarche. 2

AUB and dysmenorrhoea share underlying mechanisms involving heightened uterine contractions and vasoconstriction due to increased prostaglandin levels during endometrial shedding. 3,4

Managing AUB and dysmenorrhoea

According to Bianchi et al the same treatment approach can be used for women living with AUB and dysmenorrhoea. In patients living with primary dysmenorrhoea, initiating empirical treatment is recommended. Nonsteroidal antiinflammatory agents (NSAIDs) are considered a first-line treatment due to their ability to inhibit COX-mediated prostaglandin production. 2,3

NSAIDs are also recommended in patients living with AUB and have been shown to be effective in reduction of menstrual blood flow. If NSAIDs fail to sufficiently alleviate dysmenorrhoea symptoms, hormonal agents are recommended as a suitable first-line alternative. NSAIDs can be continued or combined with hormonal therapy as necessary. 2,5

Various hormonal contraceptives are effective for

managing dysmenorrhoea and AUB, including combined oral contraceptives (COCs) containing levonorgestrel and ethinylestradiol. This combination is indicated for the control of AUB, and the symptomatic treatment of primary dysmenorrhoea where contraception is also desired. 2,6

When used cyclically, COCs decrease menstrual blood flow. In continuous use, they significantly reduce the frequency of menstrual periods. In this regimen, women take a hormone-containing tablet daily and skip tablets without hormones, avoiding the usual stop week. This continuous method can be maintained for three to six months. If irregular bleeding occurs, women should take a break for a stop week before resuming continuous treatment. 5

COCs are effective for the treatment of dysmenorrhoea in 70%-80% of women. They work by inhibiting ovulation and preventing endometrial proliferation, which decreases prostaglandin, progesterone and vasopressin production.7

Continuous use of COCs may lead to quicker relief from pain compared to cyclic use, though both regimens can achieve long-term success in alleviating symptoms. 2

Conclusion

AUB and dysmenorrhoea are common among adolescents and young women, often co-occurring and sharing similar underlying mechanisms involving prostaglandins and uterine physiology. Effective management strategies, including NSAIDs and hormonal therapies like COCs, aim to alleviate symptoms, improve menstrual regularity, and enhance overall quality of life.

Scan the QR code on page 3 for reference lists. SF

A good ﬁ rst choice low estrogenic COC** that provides good cycle control.

Each active tablet

and

For full prescribing information, refer to the Professional Information approved by the Medicines Regulatory Authority. [1397562443c]

S4 Levette® Reg. No. 47/18.8/0525.

contains levongesterol 0,15 mg

ethinylestradiol 0,03 mg.

Tackling adult acne and hirsutism

Adult female acne (AFA), which affect ~9.8% of women, is primarily considered an inflammatory skin condition influenced by factors such as excessive sebum production, dysbiosis involving virulent strains of Cutibacterium acnes, and abnormalities in keratinocyte differentiation and proliferation, along with inflammation and innate immune responses.1

AFA is also viewed as a potential manifestation of hyperandrogenism, where increased androgen levels contribute significantly to altered sebum production, a key factor in acne pathogenesis. Apart from acne, hyperandrogenic skin symptoms include hirsutism, seborrhoea and alopecia. 2

AFA can persist from adolescence (persistent acne) or develop later in adulthood (late-onset acne), with varying clinical presentations. The condition typically manifests as either widespread superficial inflammatory lesions or localised comedones and cysts, primarily affecting the lower face and chin.1

Treatment of AFA

Hormone-based therapies for adult acne can be categorised into two main groups: Androgen synthesis inhibitors and androgen receptor antagonists. Combined oral contraceptives (COCs) are considered androgen synthesis inhibitors, primarily due to their oestrogenic components.3

Cyproterone acetate, steroidal antiandrogen combined with ethinylestradiol (EE) is indicated for the treatment of women who require anti-androgen therapy, control of idiopathic hirsutism, treatment of severe acne, especially androgen-dependent acne accompanied by inflammation, seborrhoea or the formation of nodes. 2,4

Cyproterone acetate is more potent than other antiandrogenic progestogens commonly found in COCs, leading to better clinical outcomes. EE boosts cyproterone acetate’s effectiveness by raising sex hormone-binding globulin (SHBG) levels, which reduces free testosterone and enhances Cyproterone acetate’s antiandrogenic action. 2

Efficacy in acne

Studies have shown that cyproterone acetate/EE is highly effective in treating acne, with improvements visible as early as three months and even more significant at six months. Total lesion counts decreased by 53.6% to 72%,

with non-inflammatory and inflammatory lesions reduced by 80% in one study. 2

Specific lesion types (comedones, papules, pustules, and nodules) saw significant reductions, and 90.2% of patients showed improvement. After 12 months, most patients were either free of facial acne or had only a few small lesions. These improvements were consistent whether assessed by investigators or patients. 2

Efficacy in reducing hirsutism scores

Cyproterone acetate/EE is also highly effective in reducing hirsutism scores and the frequency of shaving or hot wax treatments as early as three months. Statistically significant changes typically occur between six and 12-months, with the greatest improvements seen at 12 months, showing mean reductions (±SD) from 24.6% (±1.91) to 54.31% (±22.1). 2

One study found continuing cyproterone acetate/EE to 24-months decreased hirsutism scores from 11.8±0.6 SE to 4.7±0.6, near control levels (3.6±0.3). Facial hair responds faster. A study reported a 59% decrease in shaving or waxing after 12-months. Another study noted a 23.2% hirsutism and 36.3% acne score reduction at six months. 2

Conclusion

Cyproterone acetate/EE combination therapy is highly effective for women suffering from severe acne and symptoms of androgen excess. Cyproterone acetate/EE has shown significant improvements in acne as early as three months, with even greater results at six and twelve months. Additionally, cyproterone acetate/EE effectively reduces hirsutism scores and the need for frequent shaving or waxing, with substantial improvements noted within six to twelve months. Studies consistently highlight the benefits of cyproterone acetate/ EE, demonstrating its potency in managing both acne and hirsutism, making it a valuable treatment option for adult female acne and associated hyperandrogenic conditions.

Scan the QR code on page 3 for reference lists. SF

Your guide to using Ginette.

Frequently asked questions, answered.

S4 Reg. No. 33/21.8.2/0185. Ginette. Each blister strip of 28 tablets contains 21 active hormonal ﬁ lm-coated tablets, each with 0,035 mg ethinyl oestradiol and 2,0 mg cyproterone acetate, plus 7 inactive non-hormonal tablets. For full prescribing information, refer to the Professional Information approved by the medicines regulatory authority.

CIPLA MEDPRO (PTY) LTD. Co. Reg. No. 1995/004182/07. Building 9, Parc du Cap, Mispel Street, Bellville, 7530, RSA. Website: www.cipla.co.za Customer Care: 080 222 6662. [1397562443d]

Menopause mojo: Contraception with a twist

Perimenopause is a transition period lasting around five years and is characterised by menstrual irregularity due to a progressive decrease in follicular activity.1

Fertility around this age (40- to 44-years) is maintained, but pregnancy in perimenopause is not without risks (eg foetal malformations, chromosome abnormalities, intrauterine growth retardation, gestational diabetes, pre-eclampsia). These are good reasons for a practical and safe method of contraception.1

Formulation benefits

Improved cycle control

Discontinuation of combined oral contraceptives (COCs) due to bleeding irregularities, is not uncommon.2 COCs combine an oestrogen and a progestin component. While progestins are primarily responsible for the contraceptive effect, the oestrogenic component of a COC balances the effects of the progestin on the endometrium, resulting in a regular bleeding pattern.2 Changes in the oestrogen component of a COC, may change the stabilising oestrogenic effect on the endometrium and may consequently affect the bleeding pattern.2

Comparing 0.02mg and 0.03mg EE COC formulations

There is some evidence to suggest that ethinyloestradiol (EE) 0.02mg COC formulations, resulted in a more irregular bleeding profile compared with the higher EE 0.03mg dosage formulations. 3

Reducing the oestrogen dose to improve safety could also decrease contraceptive effectiveness and cycle control and affect the non-contraceptive benefits of COCs. 3

Predictable menstrual cycles

The 21/7 regimen offers regular monthly withdrawal bleeding, which some women prefer for predictability and for the reassurance that there is no pregnancy. This traditional COC regimen consists of 21 active pills followed by a seven-day hormone free interval (HFI). 4,5,6

Extended regimes (eg 84/7 reduced HFIs) have the same efficacy as the 21/7 regimen and is associated with high patient satisfaction due to decreased bleeding and consequent improvement in menstrual symptoms. This may be a preferred option in some older women.1,5

Non-contraceptive benefits

Recent studies reviewed support that, in addition to their contraceptive effect and improvements in menstrual symptoms, COCs have a strong and long-lasting suppressive effect on endometrial, ovarian and colorectal cancers.7

Administration of COCs (gestodene/EE in particular) in women with polycystic ovarian syndrome has proven useful because it reduces acne and hirsutism, restores cyclic regularity and improves bone density. 8

Formulations containing EE 0.03mg effectively inhibit adrenal steroidogenesis and stimulate liver production of sex hormone binding globulin than those with lower doses of EE, giving the pill a greater anti-androgenic effect.1

Safety

The increased risk for breast cancer with COC use is not consistently backed in the literature. Results range from no increase in risk to a 20%-30% elevation in risk, and the risk seems to be temporary, limited to recent or current regular COC use.7 There is evidence from some studies to show that modern COCs containing <0.05mg of EE do not increase the risk of myocardial infarction or stroke in healthy, non-smoking women regardless of age.6

The use of COCs is a consideration in older women as the risk of venous thromboembolism increases with age. Healthy women of normal weight can be prescribed a COC even at 40 to 49 years, but other potential risk factors must always be evaluated.1

Conclusion

Gestodene 0.075mg and EE 0.03mg is oral contraception indicated for the prevention of pregnancy. 5 Oral contraceptives are a safe and valid option for women as they approach menopause, who are non-smokers, enabling improved quality of life in terms of contraceptive safety, fewer vasomotor symptoms, prevention of osteoporosis, regularisation of the menstrual cycle and prevention of endometrial, ovarian and colorectal cancer.1

Scan the QR code on page 3 for reference lists. SF

Photo

Dr Ilhaam Mohamed, medical writer

A ﬁ rst-choice gestodenecontaining COC* (combined oral contraceptive) for women through to menopause1,2,3

A ﬁ rst choice gestodenecontaining COC* for young women1A,2A+B

PATIENT PROFILE

• Healthy, non-smoking 35-year-old woman - Lerato**

• On a very low dose COC* (20 µg ethinylestradiol) but experiencing breakthrough bleeding in the ﬁrst half of her cycle

• Wants a COC* that will improve cycle control and can be used continuously up to menopause

BENEFITS OF CARMADENE

• Higher ethinylestradiol improves breakthrough bleeding in the ﬁ rst half of the cycle1,4

• Better cycle control vs. 15 µg desogestrel / 20 µg ethinylestradiol3

A ﬁ rst-choice gestodenecontaining COC* for younger girls & teenagers with stable cycle control1A

PATIENT PROFILE

• Healthy, 25-year old woman

• Suﬀers from primary dysmenorrhoea and premenstrual symptoms

• Wants good cycle control and the option to delay a period when necessary

• Seeking contraception without weight gain

BENEFITS OF ACTORDENE

• A good ﬁrst choice COC* for young, healthy women1A+B

• Shown to eﬀectively reduce primary dysmenorrhoea and premenstrual symptoms3,4A

• Provides good cycle control4A

PATIENT PROFILE

• 17-year-old girl, recently became sexually active

• Heavy, painful periods

• Suﬀering from premenstrual syndrome

BENEFITS OF NESSIFEM

• Maintains cycle control with a lighter & shorter withdrawal bleed4A

• Eﬀective ovulation inhibition & contraception 3A+B

• Improves premenstrual syndrome symptoms4A

• Gestodene is androgenically neutral leading to fewer androgenic side eﬀects1C

• Suitable for healthy, non-smoking women up to menopause3

• Gestodene is androgenically neutral1

• Gestodene is androgenically neutral2D with negligible changes in body weight4B

• Can be used to delay a period

Catching cramps with COCs

Dysmenorrhoea, or menstrual pain, frequently co-occurs with premenstrual disorders (PMDs). Studies indicate that between 50%-90% of adolescent girls and young women experience dysmenorrhoea. An association between premenstrual syndrome and dysmenorrhoea in adolescent girls has been demonstrated.1

Primary dysmenorrhoea presents as recurrent lower abdominal pain during the menstrual cycle without any underlying pathology, mainly affecting adolescents within six to twelve months of menarche.1,2

Symptoms include cyclic pain starting within hours of menstruation onset, typically subsiding within 72 hours, may radiate to the lumbar area or upper legs, and may be accompanied by nausea, vomiting, diarrhea, headaches, and muscle cramps, disturbing sleep. 2

Secondary dysmenorrhoea involves menstrual pain due to underlying diseases or abnormalities within or outside the uterus. Studies show that up to 29% of women with secondary dysmenorrhoea and up to 35% with NSAIDresistant dysmenorrhoea may have endometriosis. 2

The American College of Gynecology (ACOG) recommends that when the patient’s history suggests primary dysmenorrhoea, empiric treatment should be initiated. Medical, complementary and alternative therapies are potential treatment options for pain relief.1 NSAIDs and hormonal therapies are central to managing premenstrual disorders. NSAIDs are effective in reducing menstrual pain and inflammation by inhibiting prostaglandin synthesis. Hormonal therapies, including oral contraceptives and gonadotropin-releasing hormone (GnRH) agonists, can be used to regulate menstrual cycles and reduce hormonal fluctuations.1

Further evaluation is necessary for patients with symptoms suggestive of secondary dysmenorrhoea or those who fail empiric treatment. For cases unresponsive to NSAIDs, hormonal agents are considered first-line therapy, with combined oral contraceptives (COCs) like ethinyl estradiol (EE)/drospirenone being commonly recommended.1

Momoeda et al’s study found that a flexible extended regimen of daily tablets (24 days on, four days placebo) significantly reduced dysmenorrhoeal pain days compared to the standard regimen, with both groups experiencing similar decreases in disease severity. 3

Shi et al’s review of 2251 patients found the 24/4-day EE/ drospirenone regimen effectively relieved pain symptoms compared to placebo. The flexible extended regimen further reduced dysmenorrhoea days and unscheduled bleedings without significant differences in adverse events.4

Premenstrual syndrome

PMS is characterised by physical and mood symptoms occurring in the luteal phase and resolving with the onset or during menses. PMS symptoms include changes in appetite, weight gain, abdominal and back pain, headaches, breast tenderness, nausea, constipation, anxiety, irritability, anger, fatigue, restlessness, mood swings, and crying.4,5

ACOG recommends selective serotonin reuptake inhibitors for affective symptoms and combined oral contraceptives (COCs), containing 3mg drospirenone and 20 micrograms ethinyl estradiol, for overall symptom management. ACOG also recommends GnRH agonists with adjunctive combined hormonal add-back therapy for severe, refractory premenstrual symptoms. 6

De Wit et al’s meta-analysis of nine randomised placebo-controlled trials involving 1205 participants with PMS and premenstrual dysphoric disorder found that COCs were more effective than placebo in managing overall premenstrual symptomatology.7

A Cochrane review by Ma and Song on COCs containing drospirenone found potential benefits in improving overall premenstrual symptoms and functional impairment. 8

Conclusion

With its established safety profile and minimal adverse effects, desogestrel/EE is a valuable tool for enhancing quality of life and supporting overall reproductive health among adolescent and young adult women. Desogestrel/EE has been shown to be effective in controlling menstrual cycles, dysmenorrheal pain, and regulating menstrual symptoms.

Scan the QR code on page 3 for reference lists. SF

a ﬁ rst choice desogestrel-containing COC* for women who need good & predictable cycle control1,2

a desogestrel-containing COC* for young girls who need more eﬀective cycle control1,2

PATIENT PROFILE

• Healthy 23-year-old woman, Mary

• Experiencing heavy menstrual bleeding and irregular periods

• Wants more predictable periods with less bleeding

BENEFITS OF DESIMARTM

• Provides good & predictable cycle control¹

• In nearly 110 000 cycles studied, 96-98% of withdrawal bleeds began in the ﬁ rst few days of inactive tablets, with shorter and lighter bleeding than before¹

• Incidence of irregular bleeding is low¹

• Minimal eﬀect on body weight¹

• Low incidence of side eﬀects such as nausea, headache and breast tenderness¹

PATIENT PROFILE

• Healthy, 18-year-old girl, Nazeera

• Has been on an ultra-low dose COC* for the past year but experiencing breakthrough bleeding

• Suﬀers from dysmenorrhoea and premenstrual syndrome

BENEFITS OF MERDEZATM

• Provides eﬀective cycle controlbreakthrough bleeding and spotting is limited to the ﬁ rst few cycles of use¹

• In more than 25 000 cycles studied, 95% of withdrawal bleeds began in the ﬁ rst few days of inactive tablets, with shorter and lighter bleeding than before¹

S3 Desimar™ Reg. No. 48/18.8/1041. Each active white ﬁlm-coated tablet contains desogestrel 0,15 mg and ethinylestradiol 0,03 mg. S3 Merdeza™. Each active white ﬁlm-coated tablet contains desogestrel 0,15 mg and ethinylestradiol 0,02 mg. For full prescribing information, refer to the Professional Information approved by the Medicines Regulatory Authority.[1397562443e]

Taming cycles with precision and predictability

Inadequate cycle control is the main reasons why women discontinue or switch to another oral contraceptive. Other reasons that affect the patient’s acceptance to contraceptives are its effect on their body weight and side effects associated with initiation of contraceptives are breast tenderness and headache.1

Cycle control is determined by the regularity, amount, and duration of withdrawal bleeding, as well as the incidence of irregular bleeding, and the effectiveness of delaying withdrawal bleeding.1

Combination contraception methods, in the form of oral, vaginal ring, and transdermal patch formulations, have all been shown to regulate the menstrual cycle. 2

A study by DeMaria et al found that women commonly view combined oral contraceptives (COCs) as the preferred method to control and regulate menstrual cycles. By regulating hormones, COCs enabled women to schedule menstruation according to their preference while ensuring contraception.3

Current COCs contain ethinyloestradiol (EE), combined with progestational agents such as desogestrel. All combined COCs containing new generation progestogens provide good cycle control, according to Lammers et al 1

Side effects of COCs

As mentioned, inadequate cycle control is the main reasons why women discontinue or switch to another oral contraceptive. Other reasons include the effect on body weight, breast tenderness and headache. Several studies have assessed the impact of COCs containing desogestrel, a progestin, and EE on weight gain, breast tenderness and headache.1

Weight gain

The good news is that findings consistently indicate that desogestrel/EE has minimal adverse effects on body weight. Mean changes in body weight ranged from +0.3 to +1.1 kg, and changes in body mass index ranged from +0.1 to +0.4 kg/m² over the first 18-months of treatment. Discontinuation rates due to weight gain were very low, with <1% of participants discontinuing treatment for this reason.1

Similarly, another study showed that only a small proportion of participants discontinued desogestrel/EE due to weight changes. Among those who completed 24

cycles of treatment, most experienced stable body weight, with some showing modest increases or decreases.1

Headache

Furthermore, studies show that the incidence of headaches with desogestrel/EE use was similar to those reported for other oral contraceptives. Specifically, headache incidence with desogestrel/EE was comparable to triphasic norethindrone/EE (6.1%), monophasic norgestimate/EE (29.5%), and triphasic levonorgestrel/EE (10%).1

An analysis of headache reports in the desogestrel/ EE new drug application found that most headaches were transient and short-lived, with 75% of participants reporting headaches lasting ≤1 day.1

These findings align with an epidemiologic study of >10 000 adolescents and young adults, where 77% reported experiencing a headache within the previous four weeks, with an average duration of about eight hours. Additionally, >80% of headaches in the desogestrel/EE study were classified as ‘unlikely’ to be related or ‘probably not or definitely not’ related to the agent. The discontinuation rate due to headache in this study was 3.7%.1

Breast tenderness

During treatment with desogestrel/EE, the incidence of breast tenderness was consistent across two European trials and comparable to other COCs. Specifically, the incidence rates reported for desogestrel/EE were similar to those seen with triphasic norethindrone/EE (3.1%), monophasic norgestimate/EE (6.4%), and triphasic levonorgestrel/EE (1.8%).1

Conclusion

Desogestrel/EE is a viable option for women seeking predictable cycle control with minimal impact on body weight, headaches, or breast tenderness.

Scan the QR code on page 3 for reference lists. SF

a ﬁ rst choice desogestrel-containing COC* for women who need good & predictable cycle control1,2

a desogestrel-containing COC* for young girls who need more eﬀective cycle control1,2

PATIENT PROFILE

• Healthy 23-year-old woman, Mary

• Experiencing heavy menstrual bleeding and irregular periods

• Wants more predictable periods with less bleeding

BENEFITS OF DESIMARTM

• Provides good & predictable cycle control¹

• In nearly 110 000 cycles studied, 96-98% of withdrawal bleeds began in the ﬁ rst few days of inactive tablets, with shorter and lighter bleeding than before¹

• Incidence of irregular bleeding is low¹

• Minimal eﬀect on body weight¹

• Low incidence of side eﬀects such as nausea, headache and breast tenderness¹

PATIENT PROFILE

• Healthy, 18-year-old girl, Nazeera

• Has been on an ultra-low dose COC* for the past year but experiencing breakthrough bleeding

• Suﬀers from dysmenorrhoea and premenstrual syndrome

BENEFITS OF MERDEZATM

• Provides eﬀective cycle controlbreakthrough bleeding and spotting is limited to the ﬁ rst few cycles of use¹

• In more than 25 000 cycles studied, 95% of withdrawal bleeds began in the ﬁ rst few days of inactive tablets, with shorter and lighter bleeding than before¹

The power duo: Ideal for young postadolescent women

Dr Ilhaam Mohamed, medical writer

In certain situations, the therapeutic role of oral contraceptives may be exploited, as in the case of young women with hyperandrogenism, dysmenorrhoea or premenstrual tension desiring contraception. This formulation combines gestodene for its contraceptive effects and ethinyloestradiol (EE) to stabilise the endometrium and reduce spotting.1,2

The contraceptive efficacy of oral formulations containing low dose EE (0.02mg), is in the range of 0.07-2.1. This compares favourably with the higherdose formulations containing EE 0.03-0.035mg. Pregnancy rates with gestodene-containing preparations are low and comparable with other progestogen formuations. 3,4

The ability of gestodene-containing COCs preparations to inhibit ovulation is comparable to other new progestogens like desogestrel as well as more established progestogens. Furthermore, the dosage of progestogen required to transform the endometrium appears to be lower for gestodene and desogestrel than for levonorgestrel. The efficacy and benefits of combination gestodene 0.075mg/EE 0.02mg have been highlighted in previous articles. Furthermore, in a meta-analysis based on 26 studies, combination EE 0.02mg and gestodene 0.075 mg had the lowest thrombosis risk. 4,5,6,7

Studies have shown that cycle control with COC 0.02mg formulations is comparable with a 0.03mg dosage. In addition, significantly higher discontinuation rates have not been reported for 0.02mg formulations. 3

A standard 21/7 COC regimen is designed to mimic naturally occurring menstrual cycles. Such regimens, still in widespread use, provide 21 days of active combination hormone pills followed by a hormone-free interval (HFI) of seven placebo pill and a subsequent withdrawal bleed. Some women, however, may feel that the monthly HFI is unnecessary, therefore it is possible for these women using low dose combination pills to follow a more tailored extended regimen. 8

A flexible extended regime involves extending the time between scheduled bleeding episodes which results in a lower total number of scheduled bleeding episodes (eg

21 active pills used consecutively with missed periods). Extended regimen COCs may reduce the interference of scheduled bleeding with daily activities, such as sexual activity, exercise, sports and work (including menstruationrelated absence from work) and reduce the costs and inconvenience associated with feminine hygiene products. 8

Non-hormonal benefits

COCs, besides their contraceptive role, can reduce menstrual flow and improve the regularity of the menstrual cycle. A well-documented non-contraceptive benefit of COCs is the reduction or elimination of dysmenorrhoea. Studies support the efficacy of low-dose EE 0.02mg in alleviating menstrual pain.1,2,9

Extended, flexible-extended, and continuous regimens are recognised as effective approaches to treat endometriosis, dysmenorrhoea, and menstrualrelated symptoms, offering women options to manage menstruation as desired. 8

Recent studies in premenopausal women suggest that COCs generally have minimal or no effects on low-density lipoprotein cholesterol, body mass index Homeostatic Model Assessment for Insulin Resistance, and fasting plasma glucose. Baseline lipid and glucose testing should guide the selection of the most suitable formulation for women.10

Conclusion

Oral contraceptives containing the lowest oestrogen dose is associated with the lowest incidence of side effects. The added non-hormonal contraceptive benefits suggest that EE 0.02mg and gestodene 0.075mg could be an ideal choice for young post-adolescent women.

Scan the QR code on page 3 for reference lists. SF

A ﬁ rst-choice gestodenecontaining COC* (combined oral contraceptive) for women through to menopause1,2,3

A ﬁ rst choice gestodenecontaining COC* for young women1A,2A+B

PATIENT PROFILE

• Healthy, non-smoking 35-year-old woman - Lerato**

• On a very low dose COC* (20 µg ethinylestradiol) but experiencing breakthrough bleeding in the ﬁrst half of her cycle

• Wants a COC* that will improve cycle control and can be used continuously up to menopause

BENEFITS OF CARMADENE

• Higher ethinylestradiol improves breakthrough bleeding in the ﬁ rst half of the cycle1,4

• Better cycle control vs. 15 µg desogestrel / 20 µg ethinylestradiol3

A ﬁ rst-choice gestodenecontaining COC* for younger girls & teenagers with stable cycle control1A

PATIENT PROFILE

• Healthy, 25-year old woman

• Suﬀers from primary dysmenorrhoea and premenstrual symptoms

• Wants good cycle control and the option to delay a period when necessary

• Seeking contraception without weight gain

BENEFITS OF ACTORDENE

• A good ﬁrst choice COC* for young, healthy women1A+B

• Shown to eﬀectively reduce primary dysmenorrhoea and premenstrual symptoms3,4A

• Provides good cycle control4A

PATIENT PROFILE

• 17-year-old girl, recently became sexually active

• Heavy, painful periods

• Suﬀering from premenstrual syndrome

BENEFITS OF NESSIFEM

• Maintains cycle control with a lighter & shorter withdrawal bleed4A

• Eﬀective ovulation inhibition & contraception 3A+B

• Improves premenstrual syndrome symptoms4A

• Gestodene is androgenically neutral leading to fewer androgenic side eﬀects1C

• Suitable for healthy, non-smoking women up to menopause3

• Gestodene is androgenically neutral1

• Gestodene is androgenically neutral2D with negligible changes in body weight4B

• Can be used to delay a period

Clear skin and peace of mind: The next generation of contraception

Dr Ilhaam Mohamed, medical writer

Although combined oral contraceptives (COCs) provide effective contraception, adherence and continuity of use depend on the incidence and severity of sideeffects (the risk of venous thrombosis and oestrogen related side effects).1

New formulations aim to minimise the oestrogen related side-effects by decreasing the oestrogen dosages and using a progestin component with a more favourable metabolic profile and reduced systemic effects.1

This formulation is a new generation COC with a combination progestin component drospirenone, and an oestrogen component ethinylestradiol (EE).1

The progestin component suppresses ovulation while the oestrogen component is added for cycle control. Oestrogen also has an additive effect on suppression of the follicular development while preventing spotting and decreasing menstrual blood loss.1

Formulation benefits

Compared with the conventional 21/7 regimen, the 24/4 regimen results in greater inhibition of ovulation and lower fluctuations in hormone levels. The 24/4 regimen enables a lower oestrogen dosage (0.02mg EE), ensuring good cycle control while decreasing oestrogen-related side effects. 2

Drospirenone combines progestogenic, antimineralocorticoid, and anti-androgenic effects, providing non-contraceptive benefits. It is safe to use and has a low discontinuation rate due to bleeding compared with other 0.02mg COC formulations. 2

A recent meta-analysis showed that DSRP/EE has a good safety profile, including low risk of thrombus, weight gain, or water retention, good tolerability, and a low overall risk of adverse events. The results also demonstrated that the combination could improve symptoms of dysmenorrhea and decrease other related pain symptoms. Safety data align with findings from another recent meta-analysis. 2,3

Anti-mineralocorticoid activity

Drospirenone is an aldosterone antagonist at the mineralocorticoid receptor. By opposing the sodiumretentive effect of EE, drospirenone may help prevent the water retention, weight gain and increased blood pressure sometimes associated with oral contraceptive use. 4,5

Antiandrogenic activity and acne treatment

Anti-androgenic activity of COCs is associated with both the oestrogen and progestin components. Oestrogen stimulates sex hormone binding globulin liver synthesis which reduces testosterone production by the ovaries. Progestins lower the levels of gonadotropins, which are hormones involved in regulating sex hormone production.6

Drospirenone 3mg and EE 0.02mg EE/ is indicated for treating moderate acne vulgaris. Studies show that the formulation resulted in improvement in acne, significant improvement in trunk acne and significant reduction of skin problems treatment costs. drospirenone was more effective than chlormadinone acetate in the treatment of skin changes such as seborrhoea, acne, increased hair, hydration, homogeneity, and overall quality of the skin. 4,6

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome affecting up to 7% of reproductive age women. The disorder is characterised by moderate to severe psychological, behavioural and physical symptoms beginning up to two weeks prior to menses, resolving soon after the onset of menstruation and significantly interfering with daily functioning.7

The oral contraceptive with the most evidence for efficacy in treating PMDD is the drospirenone 3mg/EE 0.02mg 24/4 pill formulation. It is advantageous because of the lower dose EE, shorter hormone free interval and the spironolactone-like activity of drospirenone, with antimineralocorticoid and anti-androgenic properties.7,8

Conclusion

Drospirenone/EE is a newer COC formulation and in addition to contraception, is indicated for the treatment of moderate acne vulgaris in women seeking oral contraception and is beneficial in the treatment of symptoms of PMDD in women who have chosen oral contraception as their method of birth control.9

Scan the QR code on page 3 for reference lists. SF

Progesterone support in ART

About 85% of women can conceive within 12-months of unprotected intercourse. The American Society of Reproductive Medicine recommends initiating an evaluation for infertility after failing to achieve pregnancy within 12-months of unprotected intercourse or therapeutic donor insemination in women <35-years, or within six months in women >35- years.1

Infertility statistics

In girls and women aged between 15- to 34-years, infertility rates range from 7.3% to 9.1%. In women aged between 35- to 39-years, infertility rates increase to 25%. Lastly, women aged between 40- to 44-years have a 30% chance of infertility. Worldwide, 2% of women aged between 20- to 44-years will never be able to have a live birth, and 11% with a previous live birth are unable to have an additional birth.1

Infertility evaluations

Initial assessments involve medical histories and physical exams. Female infertility evaluations are intricate, often starting with confirming ovulation and assessing uterine and tubal structure via ultrasound or hysterosalpingogram. Hormonal evaluations help diagnose ovulatory dysfunction. 2 Despite comprehensive testing, the root cause of infertility may remain elusive. According to the World Health Organization (WHO) the most common causes of female infertility include:1,2

_ Ovulatory disorders – 25%

_ Endometriosis – 15%

_ Pelvic adhesions – 12%

_ Tubal blockage – 11%

_ Other tubal/uterine abnormalities – 11%

_ Hyperprolactinaemia – 7%.

ART as infertility treatment

Assisted reproductive technologies (ART) – particularly in vitro fertilisation (IVF) – have gained widespread acceptance as the treatment of choice depending on the cause.2 ART accounts for up to 8% of children born in some countries. ART involves creating embryos in the laboratory and transferring them to the uterus to facilitate pregnancy. 3 IVF constitutes 33.3% of ART cycles. In IVF, ovarian stimulation is first conducted to retrieve multiple eggs during a single cycle. Once eggs are extracted, a sperm sample is obtained. Following this, eggs are fertilised outside the body in a Petri dish to form embryos. 2

everywoman, everystage

Progesterone pessaries

S4 Reg. No. Z/21.8.2/294. CYCLOGEST® 200 mg (Pessaries). Each pessary, suitablefor vaginal insertion, contains 200 mg progesterone Ph.Eur. For full prescribing information, refer to the Professional Information approved by the medicines regulatory authority.

CIPLA MEDPRO (PTY) LTD. Co. Reg. No. 1995/004182/07. Building 9, Parc du Cap, Mispel Street, Bellville, 7530, RSA. Website: www.cipla.co.za Customer Care: 080 222 6662. [1397562443g]

Typically, one or more embryos are transferred into the female’s uterus, while any extra embryos can be frozen for future use, eliminating the need for additional ovarian stimulation and egg retrieval. Various methods exist for selecting sperm during the IVF process. 2

Sufficient luteal phase support essential for successful outcome

A significant challenge in ART cycles is achieving sufficient luteal phase support (LPS) following ovarian stimulation. During natural menstrual cycles, progesterone levels rise naturally to prepare the endometrium for implantation and sustain early pregnancy. 4

However, in ART cycles involving IVF, supra-physiologic oestrogen levels during ovarian stimulation can disrupt this process, leading to an insufficient luteal phase. This deficiency can impair implantation and reduce pregnancy rates.4

To address this challenge, LPS is administered using progesterone or alternatives like human chorionic gonadotropin or gonadotropin-releasing hormone agonists.4

Progesterone transforms proliferative endometrium (oestrogen effect) into secretory endometrium. This prepares the endometrium for pregnancy implantation. 5

Progesterone, delivered via various routes including vaginal, intramuscular (IM), oral, or rectal, is commonly used due to its safety and efficacy in maintaining pregnancy.4

Several studies have explored different aspects of LPS in ART assisted reproduction, highlighting varying outcomes based on progesterone administration. A meta-analysis involving eight randomised controlled trials, and 875 participants showed that progesterone LPS significantly increased ongoing pregnancy rates compared to placebo or no treatment (odds ratio [OR] 1.77). This effect became more pronounced when progesterone was continued beyond the initial pregnancy test until 12 weeks (OR 2.17).6

In studies comparing different routes of progesterone administration in fresh embryo transfers, no significant differences were found between IM vs oral, or IM vs vaginal/rectal routes. Recent retrospective studies also demonstrated similar outcomes between combined IM and vaginal progesterone vs either IM or vaginal progesterone alone. 6

In South Africa, progesterone is available as micronised oral tablets (100mg), vaginal pessaries (200mg micronised progesterone) and vaginal gel 8% (90mg per application). 5

Vaginal progesterone preferred

Despite the comparable efficacy of different administration routes, patient preference, side effects

such as injection site reactions, and variable absorption must be considered when optimising LPS protocols in ART cycles. The oral route has lower bioavailability (<10%) and a higher incidence of side effects, compared to the vaginal route, which is not only effective, but also painless. Daily IM administration is often linked to severe discomfort and, in rare cases, sterile abscesses and secondary infection. 4,6,7

The vaginal route allows for easy administration and rapid progesterone absorption across the epithelium with the first uterine pass, avoiding first-pass hepatic metabolism that can lead to progesterone inactivation. The vaginal route also limits systemic exposure.7

According to a survey involving 408 IVF units across 82 countries, clinicians and patients prefer vaginal progesterone (used in 77% of 284 600 IVF cycles). 4

Vaginal pessaries

A study by Khrouf et al showed that vaginal pessaries demonstrate a lower miscarriage rate (6.3%) compared to vaginal capsules (27.3%) and rectal pessaries (27.3%).9

Progesterone pessaries are specifically recommended for women undergoing ART programmes in South Africa. The standard dosage is 400mg administered twice daily via vaginal insertion, commencing on the day of egg retrieval. In cases where pregnancy is confirmed, progesterone administration should continue for 38 days from the initiation of therapy.10

Conclusion

Achieving LPS is crucial for enhancing the success of IVF cycles. Progesterone plays a pivotal role in preparing the endometrium for embryo implantation and sustaining early pregnancy.

Vaginal pessaries, a preferred form of progesterone administration in many ART protocols, offer distinct advantages over other routes such as oral delivery. They ensure efficient absorption directly through the vaginal epithelium, bypassing hepatic metabolism that could otherwise deactivate the hormone. This method not only enhances local progesterone concentrations but also minimises systemic exposure, potentially reducing side effects.

Furthermore, studies have indicated lower miscarriage rates associated with vaginal pessaries compared to alternative forms of progesterone administration. In South Africa, progesterone pessaries are integral to ART protocols, administered vaginally at specific doses tailored to support embryo implantation and early pregnancy maintenance.

Scan the QR code on page 3 for reference lists. SF

Deciphering AUB

Abnormal uterine bleeding (AUB) is a prevalent, debilitating condition affecting ~50% of reproductive-aged women worldwide. It has an array of symptoms including irregularities in menstrual bleeding and abnormalities in the duration of periods, which may lead to iron defiency and related anaemia.

Societal taboos, healthcare professionals’ dismissal of symptoms, and a general lack of awareness about treatment options often lead to the normalisation of AUB among women. AUB can manifest as chronic or acute bleeding disturbances. Chronic AUB refers to abnormal bleeding from the uterine corpus that persists for the majority of the past six months, while acute AUB involves episodes of heavy bleeding requiring immediate intervention to prevent further blood loss. These distinctions help guide clinical management and treatment strategies tailored to the individual’s needs. The onset of AUB commonly occurs during significant reproductive transitions such as menarche and peri-menopause. Regardless of the primary cause, AUB in reproductive years typically originates in the endometrium. Understanding the physiological changes and hormonal fluctuations associated with these life stages is essential for effectively managing AUB and addressing its underlying causes.1,2

AUB has a significant impact on affected women’s quality of life. Despite its prevalence, many women avoid seeking treatment or consultation, with a significant percentage feeling their concerns are inadequately addressed by healthcare professionals. Initiating conversations about menstruation can be challenging due to societal discomfort and cultural taboos. Taking a structured history that includes details about bleeding patterns, associated symptoms, and the impact on daily activities is the first step in assessing and managing AUB.2,3

Following history-taking, conducting a comprehensive gynaecological and medical assessment is necessary to identify potential underlying causes of AUB. This may involve physical examinations, laboratory tests, and imaging studies to evaluate for structural abnormalities, hormonal imbalances, or systemic disorders contributing to abnormal bleeding.2 Collaborating with specialists may be necessary for further evaluation and management, particularly in cases involving coagulation disorders or suspected malignancy.2

Treatment options

Medical management is often the first-line approach for treating AUB. Hormonal therapy plays a significant role in managing AUB, especially in cases where gonadal steroid

activity needs to be manipulated. One commonly used hormonal therapy is the levonorgestrel-releasing intrauterine system (LNG-IUS), which releases low-dose levonorgestrel locally to suppress endometrial activity.4,5

The LNG-IUS is effective in reducing menstrual blood loss and provides reliable contraception without impacting fertility, making it a suitable choice for many women.4

Where oestrogen-containing formulations are contraindicated, single-agent progestogens may provide a viable option for some causes of AUB. There are several formulations and administration schedules, and some have been evaluated to determine their ability to provide symptom control. While less effective than the LNG-IUS, combined hormonal contraceptives are well tolerated by most women and can be used continuously to reduce the frequency of withdrawal bleeds. For women who cannot use oestrogencontaining formulations, progestogen-only therapies may be prescribed. These include oral progestins given cyclically or continuously, as well as injectable or implantable progestogens. Progestogen-only therapies effectively reduce menstrual blood loss and are suitable for women with contraindications to oestrogen-containing formulations. Gonadotropin-releasing hormone (GnRH) modulators, such as GnRH agonists and antagonists, are used to create a temporary menopausal state by suppressing gonadal steroid production.

Selective progesterone receptor modulators are synthetic steroids that act on progesterone receptors, reducing uterine bleeding and fibroid size. However, their use may be limited due to potential adverse effects, such as liver disease.4

In cases where medical management is ineffective or contraindicated, procedural interventions offer alternative treatment options. Endometrial ablation, hysteroscopic removal of structural lesions, and uterine-conserving surgeries like myomectomy provide minimally invasive approaches for managing AUB while preserving fertility.4

Image-guided procedures such as hyperthermic ablation and uterine artery embolization offer non-surgical options with potential benefits for symptom relief, although their impact on future fertility requires consideration.4

Scan the QR code on page 3 for reference lists. SF

Complexities of endometriosis

Endometriosis, a complex and often misunderstood disease, profoundly impacts the lives of affected women. Endometriosis negatively affects fertility, sexuality, ability to work and personal relationships. Symptoms are often overlooked, leading to delayed diagnosis (up to seven years).1,2,3

Stigmatisation of endometriosis contributes to delayed diagnosis.4 To prevent stigma related to menstruation and endometriosis, women have developed strategic ways to manage information about their menstrual cycles, a practice known as ‘menstrual etiquette’.4

Women reported needing to manage heavy bleeding and pelvic pain during workdays to avoid getting into trouble. They expressed feelings of embarrassment and judgment from colleagues, who sometimes accuse them of malingering and shirking work responsibilities. 4

Endometriosis affects ~10% of women of reproductive age. 2 Symptoms include intense dysmenorrhea, dyspareunia and chronic pelvic pain. 2 The disease is characterised by the presence of endometrial-like tissue outside the uterus, leading to inflammation, scarring, and adhesions in pelvic structures. 2

Endometriosis-related pain

For women experiencing endometriosis-related pain, the 2024 update National Institute of Health and Care Excellence (NICE) guideline recommends a short trial (eg three months) of paracetamol or a non-steroidal anti-inflammatory drug (NSAID), either alone or in combination, as first-line treatment for endometriosis-related pain.5

If the trial of paracetamol or NSAIDs (alone or in combination) does not provide sufficient pain relief, the guideline recommends exploring other pain management options such as neuromodulators to manage neuropathic pain5 and referring the patient for further assessment.5

Several guidelines and medical societies including the NICE guidance,5 the European Society of Human Reproduction and Embryology (ESHRE)6 and the American College of Obstetricians and Gynecologists (ACOG)7 recommend hormonal treatment for the management of endometriosisrelated pain.

NICE recommends combined oral contraceptives (COCs) or progestogen.5 ESHRE recommends combined hormonal contraceptives include COCs, the vaginal ring (levonorgestrelreleasing intrauterine system) or transdermal contraceptives (etonogestrel-releasing subdermal implant), as well as progestogens and gonadotropin hormone-releasing

hormone (GnRH) agonists, or GnRH antagonists.6

Furthermore, recommends ESHRE, clinicians should use a shared decision-making approach, considering individual preferences, side effects, efficacy, costs, and availability when selecting hormone treatments for endometriosis-associated pain. Combined hormonal contraceptives are recommended to reduce endometriosis-associated dyspareunia, dysmenorrhoea, and non-menstrual pain. Continuous use of COCs can be offered for endometriosis-associated dysmenorrhoea. ESHRE cautions that if progestogens are considered, clinicians should assess the different side effect profiles before prescribing them. GnRH agonists are recommended to reduce endometriosis-associated pain, although evidence on dosage and duration is limited.6

GnRH agonists should be prescribed as a second-line treatment if hormonal contraceptives or progestogens have been ineffective due to their side effect profile. Combined hormonal add-back therapy is recommended alongside GnRH agonists to prevent bone loss and hypo-oestrogenic symptoms. For women with pain refractory to other medical or surgical treatments, aromatase inhibitors are recommended as they reduce endometriosis-associated pain and may be prescribed in combination with COCs, progestogens, GnRH agonists, or GnRH antagonists.6

Conclusion

Endometriosis significantly impacts the lives of affected women. It is associated with symptoms like intense dysmenorrhoea, dyspareunia, and chronic pelvic pain. The stigma surrounding the disease compels women to adopt ‘menstrual etiquette’ to manage symptoms discreetly, leading to further challenges at work and in personal relationships. Effective pain management involves a tiered approach, starting with paracetamol or NSAIDs and progressing to hormonal treatments and neuromodulators as recommended by guidelines from NICE, ESHRE, and ACOG. Hormonal treatments, including combined hormonal contraceptives, progestogens, and GnRH agonists, are essential for reducing endometriosisassociated pain and improving quality of life.

Scan the QR code on page 3 for reference lists. SF

INSIGHTS FOR DERMATOLOGISTS

The complex relationship between contraceptive use and acne

Acne vulgaris, a multifactorial skin disorder affecting millions worldwide, poses significant challenges for dermatologists in its management and treatment.

Among the myriad of factors contributing to acne development, hormonal fluctuations play a pivotal role. One area of particular interest is the relationship between contraceptive use and acne.

As dermatologists, understanding this intricate interplay is crucial for providing comprehensive care to patients. This article aims to explore the complexities of this relationship, shedding light on the mechanisms involved,

Dr Lushen Pillay, Department of Dermatology, University

of the Witwatersrand

the impact of various contraceptives on acne, and practical implications for clinical practice.

Hormonal influences on acne

Before delving into the connection between contraceptives and acne, it’s imperative to grasp the hormonal underpinnings of acne pathogenesis. Androgens, particularly testosterone and its derivatives, exert a profound influence on sebaceous

gland activity, keratinocyte proliferation, and inflammation, all of which are central to acne development.

Elevated androgen levels increase sebum production, leading to follicular hyperkeratinisation and subsequent comedone formation – the hallmark of acne lesions.

Contraceptives and hormonal balance

Contraceptives, notably combined oral contraceptives (COCs) containing oestrogen and progestin, are widely prescribed for contraception and various gynaecological conditions.

By modulating hormonal levels, COCs suppress ovulation, stabilise endogenous hormone fluctuations and alter the androgen-to-oestrogen ratio. These mechanisms hold promise for managing acne, particularly in individuals with hormonally driven acne or those with premenstrual exacerbations.

Impact of contraceptives on acne

The effects of contraceptives on acne can vary depending on the specific formulation, progestin type, and individual patient characteristics. COCs containing anti-androgenic progestins such as drospirenone or cyproterone acetate have demonstrated efficacy in reducing sebum production and mitigating acne severity.

Conversely, progestins with higher androgenic activity, such as norgestrel or levonorgestrel, may exacerbate acne in susceptible individuals. Non-oral contraceptives, such as the levonorgestrel-releasing intrauterine system (LNG-IUS), have also shown mixed results regarding acne improvement, warranting careful consideration in clinical decision-making.

Patient selection and counselling

When considering contraceptive options for patients with acne, a tailored approach based on individualised patient characteristics and acne severity is paramount.

Factors such as age, menstrual irregularities, contraceptive preferences, and comorbidities should inform the selection of an appropriate contraceptive regimen.

Dermatologists should engage in comprehensive discussions with patients, highlighting the potential benefits, risks, and side effects of contraceptives, including their impact on acne. Shared decision-making empowers patients to make informed choices aligned with their reproductive and dermatological health goals.

Combination

therapy and multimodal approaches

In cases where acne management necessitates a

multifaceted approach, combining contraceptives with topical or systemic acne treatments may yield synergistic benefits.

Topical retinoids, benzoyl peroxide, and antimicrobial agents can complement the anti-androgenic effects of contraceptives by targeting different pathogenic pathways involved in acne pathogenesis. Systemic therapies, such as oral antibiotics or isotretinoin, may be considered in severe or recalcitrant cases, with close monitoring for potential drug interactions and adverse effects.

Monitoring and follow-up

Regular follow-up visits are crucial for assessing treatment response, monitoring for adverse effects, and adjusting the contraceptive regimen as needed.

Dermatologists should collaborate closely with gynaecologists or primary care providers to optimise contraceptive management while concurrently addressing acne-related concerns.

Objective measures, such as acne lesion counts, global assessment scales, and patient-reported outcomes, facilitate ongoing evaluation and treatment optimisation, fostering a patient-centred approach to care.

Considerations in special populations

Certain patient populations warrant special consideration when prescribing contraceptives for acne management. Adolescents and young adults, for instance, may benefit from early intervention to mitigate psychosocial sequelae associated with acne.

Additionally, individuals with polycystic ovary syndrome (PCOS), a common endocrine disorder characterised by hyperandrogenism, menstrual irregularities, and acne, may derive therapeutic benefits from COCs targeting androgen excess while addressing contraceptive needs.

Conclusion

The intricate interplay between contraceptive use and acne underscores the importance of a nuanced approach in dermatological practice. By understanding the hormonal influences on acne pathogenesis and the diverse effects of contraceptives on hormonal balance, dermatologists can effectively integrate contraceptive options into comprehensive acne management strategies.

Through patient-centred care, shared decision-making, and multidisciplinary collaboration, dermatologists play a pivotal role in optimising outcomes and enhancing the quality of life for individuals affected by acne.

Scan the QR code on page 3 for reference lists. SF

Your guide to using Ginette.

Frequently asked questions, answered.

CIPLA MEDPRO (PTY) LTD. Co. Reg. No. 1995/004182/07. Building 9, Parc du Cap, Mispel Street, Bellville, 7530, RSA. Website: www.cipla.co.za Customer Care: 080 222 6662. [1397562443d]

The contemporary management of menopause

Tobie de Villiers, Past-president of the International Menopause Society and Consultant Gynaecologist, MediClinic Panorama

Management of the menopause is a highly debated topic. This has been highlighted in the past months by an editorial in The Lancet titled: Time for a Balanced Conversation about Menopause. They argue that although menopause is a natural phase of life, commercial companies and individuals with vested interests have over-medicalised the menopause, framing it as a disease of oestrogen deficiency that can be eased only by menopausal hormone therapy (MHT), while downplaying risks of such therapy. Photo credit:

Although not directly named, The Lancet editors imply that the menopause societies of the world are part of this conspiracy. Nothing is further from the truth. A consensus statement by the major players in the field in 2013 stated that the option of MHT is an individual decision in terms of quality of life and health priorities as well as personal risk factors such as age, time since menopause and the risk of venous thromboembolism, stroke, ischaemic heart disease and breast cancer.

This opinion has been repeated in the guidelines of many national and international menopause societies since then. The International Menopause Society (IMS) responded to The Lancet editorial by agreeing that women should be counselled and have access to the full armamentarium of treatment options such as lifestyle, diet, exercise, cognitive behavioural therapy (CBT), complementary therapies, MHT and non-hormonal pharmacological options.

However, the claim that the principles of health empowerment have not been applied to the menopause is not only inaccurate, but also derogatory to the many menopause healthcare practitioners who take great care in ensuring that patients are intimately involved in the decision-making process during counselling.

It also shows lack of recognition of the work that the IMS and many national societies have been undertaking for more than a decade to provide accessible, credible information about the menopause to empower women.

The basic knowledge of the menopause that enables mutual decision making will be summarised in the rest of this text.

Physiology

The Stages of Reproductive Aging plus 10 is regarded as the gold standard in terminology of the menopause. The final menstrual period (menopause) is a retrospective diagnosis made after 12 months of amenorrhoea and this marks the start of the postmenopause period. The menopause can occur between the ages of 45 and 55 years.

It is a clinical diagnosis that needs no biochemical confirmation. In the absence of a uterus, follicle-stimulating hormone (FSH) value >25 IU/l six weeks apart is suggestive of the menopause. The perimenopause (transitional period) follows the reproductive period that is defined by the start of menstrual irregularities and stretches till one year after the final menstrual period.

The postmenopause is defined by complete ovarian oocyte depletion with absent levels of estrogen and progesterone and raised levels of FSH, resulting in predictable clinical symptoms. The perimenopause results from gradual depletion of oocytes with highly variable levels of estrogen, progesterone and FSH, with abrupt increases and decreases that result in a hormonal rollercoaster.

The menopause is thus an inevitable natural occurrence that heralds a new phase in the life of every woman.

Tibolone Actor is a synthetic steroid. Post absorption, it’s metabolites have estrogenic, progestogenic and androgenic properties.

Tibolone Actor is indicated for

• Symptomatic treatment of hot ﬂ ushes and associated sweating resulting from natural or surgical menopause

• Prevention of post-menopausal osteoporosis

• Improvement of bonemineral density in patients with established post-menopausal osteoporosis

• Tibolone Actor improves sexual well-being, mood, fatigue and malaise4

• Tibolone Actor is bioequivalent to the originator⁵

For full prescribing information, refer to the Professional Information approved by the Medicines Regulatory Authority. [1397562443k]

Tibolone Actor. Registration number: 48/21.13/0297. Each tablet contains 2.5 mg Tibolone..

The evolutionary significance remains uncertain.

Although the age at the menopause has remained fairly constant, life expectancy has improved dramatically in the last century, resulting in an increasing and significant number of menopausal women who play an important part in society and the workplace.

Consequences of the menopause

The common denominator of life after the menopause is the total absence of ovarian derived oestrogen. Although this is not a disease, the biological changes that occur at the menopause may greatly influence quality of life (QoL) and general health or both.

Vasomotor symptoms (VMS), also called hot flushes (or flashes), are the hallmark symptoms of the menopause. VMS affect the majority of menopausal women, but severity may range between mild, moderate and severe.

VMS may start in the peri- or postmenopausal period. VMS may last for five to eight years but for some it will never disappear. In affected women, it is a cause of distress with lowering of QoL. VMS are also associated with adverse effects on other systems such as the cardiovascular (CV) system.

Loss of oestrogen causes stimulation of the Kisspeptin, neurokinin B, and dynorphin neurons with overexpression of the neurokinin B/neurokinin-3-receptor (NKB/NK3R) chemical pathway with resultant narrowing of the hypothalamic thermoregulatory unit. A hot flush represents dissipation of heat to lower core body temperature.

Several other conditions are related to the early menopause or changes during this period of life, such as cognitive changes, anxiety, depressive symptoms, sleep disturbances, migraine and musculoskeletal pain. Intermediate consequences of the menopause include genitourinary syndrome of menopause (GSM) with later consequences osteoporosis, adverse CV health and dementia.

Options to be discussed at start of menopause

Non-hormonal options

Lifestyle modifications such as weight maintenance, environmental control, avoiding triggers of VMS, exercise, CBT, complementary therapies, dietary management or supplements, have been suggested in the management of VMS but evidence for the effectiveness is mixed, limited or non-existent.

Various serotonin norepinephrine reuptake inhibitors including paroxetine, escitalopram, citalopram, venlafaxine, desvenlafaxine, sertraline and fluoxetine have shown reduction in hot flushes ranging from 25% to 69%,

with improvements in composite hot flush frequency and severity from 27% to 61%, whereas less consistent results have been seen with gabapentin and clonidine. NKB/NK3R antagonists are not yet available in South Africa.

Hormonal options

MHT including tibolone

Although initial findings from the Women’s Health Initiative study (WHI) have been widely (and persistently) misinterpreted, subsequent age-stratified analysis of WHI data supports MHT is as first line treatment of VMS of menopause.

MHT significantly alleviates VMS when compared to placebo or other available non-hormonal options. MHT protects the urogenital system, bone, and CV system, has beneficial effects on sleep and mood disorders, and may offer protection against colorectal cancer.

Although the most common indications for MHT are the treatment of VMS or GSM and the prevention of osteoporosis, beneficial effects on the CVS and brain and other effects of aging should always be part of the conversation.

MHT may slightly increase the risk of thromboembolic disease and the promotion of pre-existing breast cancer. These effects can be mitigated by initiating MHT within the window of opportunity (<60 or within 10 years of the menopause), by using the transdermal route, oestrogen alone (no uterus) or combined with natural progesterone or dydrogesterone (uterus intact), and by using the minimum effective dose. There are no limits to the length of use of MHT.

Continuation of MHT >65 years has recently been shown to be significantly beneficial compared to non-users. The use of compounded MHT is not supported because of no proven benefits compared to regulated MHT, undocumented sideeffects and lack of regulatory oversight.

Conclusion

The menopause is indeed a natural and inevitable event. The initial event’s nature is highly variable, ranging from no significant adverse experiences to unbearable lifedisturbing symptoms. In the long term, all postmenopausal women will suffer specific changes induced by lack of oestrogen apart from the normal effects of ageing.

It is the right of every postmenopausal woman to be fully informed about expectations of this phase of her life as well as available interventions to be able to make an individual informed decision. The initial discussion is time-consuming and may be best continued at a second consultation. Very often contemporary management of the menopause is more about talking than doing. Scan the QR code on page 3 for reference lists.

Countless women grapple with urinary issues every day

Millions of women worldwide experience lower urinary tract symptoms (LUTS), which significantly impact their quality of life (QoL). A recent metaanalysis revealed that the prevalence of LUTS among women globally varies widely, ranging from 11.8% to 88.5%.1

Non-neurogenic LUTS include storage, voiding, and post-micturition symptoms, categorised into several clinical syndromes such as overactive bladder (OAB), underactive bladder, urinary incontinence (UI), nocturia, dysfunctional voiding, or genitourinary fistulae. 2

Storage symptoms include frequency, urgency, nocturia, and UI, which can be further classified as stress UI (SUI), urgency UI (UUI), or mixed UI (MUI). Voiding symptoms consist of hesitancy, intermittent, slow stream, straining, splitting or spraying of the urinary stream, and terminal dribbling. Post-micturition symptoms include post-void dribbling and a feeling of incomplete bladder emptying. 2

SUI is the most common form of LUTS affecting up to 31.8% of women. The prevalence of UUI and MUI ranges from 0.7% to 24.4% and 2.1% to 12%, respectively.1

Risk factors

Most women report experiencing symptoms sometimes (76.3%) or often (52.5%). Various risk factors for LUTS have been identified, including age, marital and work status, comorbidities, alcohol consumption, higher parity, vaginal delivery, instrumental delivery, prolonged labour, laceration, and post-menopausal status.1

Impact on QoL

The psychological impact of LUTS is profound, with studies indicating heightened anxiety and depression among affected individuals. Women with OAB report feeling anxious and depressed about their condition compared to those without urinary dysfunction.3 Nocturia, defined as the frequent need to urinate at night. Nocturia can lead to sleep deprivation, which can cause exhaustion, mood changes, drowsiness, impaired productivity, increased risk of falls and accidents, fatigue, lethargy, inattentiveness, and cognitive dysfunction.4

Diagnosing LUTS

Diagnosing LUTS involves a comprehensive approach, including history-taking, physical examination, and validated questionnaires. Various diagnostic tools such as

bladder diaries, urinalysis, and post-void residual volume measurements aid in accurate assessment. 2

Management of LUTS

Management of LUTS in women focuses on addressing associated medical comorbidities, lifestyle modifications, and pharmacotherapy. Conservative measures such as prompted voiding, bladder training, and pelvic floor muscle training are integral components of comprehensive care. 2

First-line pharmacotherapy includes anticholinergic agents, which are available in different formulations. Immediaterelease formulations offer dosage flexibility but are associated with more adverse effects compared to extendedrelease formulations. Despite their effectiveness in improving LUTS, antimuscarinics can lead to adverse effects like dry mouth, cognitive impairment, and urinary tract infections.2

Beta-3 agonists, particularly mirabegron, offer an alternative pharmacological approach for LUTS management. Mirabegron has shown efficacy in reducing urgency episodes, urinary incontinence episodes, and micturition frequency with a favourable safety profile compared to anticholinergics. Concerns about cognitive function associated with prolonged anticholinergic use highlight the importance of considering the anticholinergic burden when prescribing medications for LUTS.2

Additionally, hormone therapy, particularly vaginal oestrogen therapy, has demonstrated benefits in managing genitourinary symptoms of menopause, including urogenital symptoms associated with LUTS. Alternative treatment modalities such as botulinum toxin injections and sacral nerve stimulation have shown promise in refractory cases.2

Conclusion

In conclusion, LUTS in women pose significant challenges, affecting millions worldwide. A multidimensional approach is essential for effectively managing LUTS, considering individual characteristics and preferences. Continued research and innovation are crucial for improving outcomes and enhancing the quality of life for women living with LUTS.

Scan the QR code on page 3 for reference lists. SF

Photo credit: Shutterstock.com

Fluctuating hormones and female emotionality

Women are disproportionately affected by anxiety and depression compared to men, with a two-fold increased risk. Fluctuating hormone levels dynamically impact female brain morphology and are likely contributors to female-specific risks for neuropsychiatric conditions such as depression and anxiety disorders.1

Certain types of depression, such as premenstrual dysphoric disorder (PMDD), postpartum depression (PPD), and menopause-associated depression, are unique to women, further highlighting the impact of hormones on mental health. 2

Fluctuating hormones

Throughout the menstrual cycle, women experience fluctuations in sex hormone levels, particularly oestrogen and progesterone. These hormones have potent neuromodulatory effects and shape female emotionality. The menstrual cycle, typically lasting 28-35 days, consists of a follicular phase (high oestrogen, low progesterone) and a luteal phase (low oestrogen, high progesterone).1

Protective effect of oestrogen

Oestrogen, in particular, has protective effects against

anxiety and depression. It has been shown to have anxiolytic- and antidepressant-like effects,1 and its decline, as seen during menopause, can negatively affect women’s psychological well-being. Studies have indicated that during menopause, sex hormones, especially 17β -oestradiol, substantially decline in the body and brain, leading to various neurological changes. 3

Depressive disorders unique to women

PMDD symptoms include marked mood swings, sudden sadness or tearfulness, increased sensitivity to rejection, irritability or anger, increased interpersonal conflicts, depressed mood, feelings of hopelessness or selfdeprecating thoughts, anxiety, tension, or feeling on edge.4

Furthermore, there may be decreased interest in usual activities, difficulty concentrating, lethargy, fatigue, lack of energy, changes in appetite, overeating or specific food

cravings, hypersomnia or insomnia, feeling overwhelmed or out of control, and physical symptoms like breast tenderness, swelling, joint or muscle pain, bloating, or weight gain.4

These symptoms must cause significant distress or interfere with work, school, social activities, or relationships. These symptoms are closely tied to hormonal fluctuations, particularly the decline in progesterone levels during the luteal phase. 4

PPD occurs within six weeks following childbirth and is associated with changes in the reproductive hormones such as oestradiol and progesterone, which stimulate the dysregulation of these hormones in sensitive women. The hormonal changes during pregnancy and childbirth, coupled with psychological stressors, contribute to the onset of depression in the postpartum period.

During menopause transition, women experience significant hormonal changes, including declines in sex hormones like oestrogen. These hormonal fluctuations, along with other factors such as history of depression and anxiety, contribute to the onset of new mood disorders during this stage of life. 6

Studies have shown that neuroticism, a personality trait associated with negative mood and anxiety, are risk factors for menopausal decompensation with depression.7

Treatment strategies

For conditions like PMDD and PPD, selective serotonin reuptake inhibitors and combined oral contraceptives, with gonadotropin releasing hormone agonists, are recommended for refractory cases. 8

Hormone replacement therapy is another treatment option, particularly for menopause-associated depression, as it can help restore hormonal balance and alleviate symptoms.9

Furthermore, psychotherapy 9 is often recommended as part of a comprehensive treatment plan, helping women cope with the emotional challenges associated with hormonal fluctuations and mood disorders.

Conclusion

Hormonal influences play a significant role in the development and treatment of depression in women. Fluctuations in sex hormone levels throughout the menstrual cycle, pregnancy, and menopause can impact mood and emotional well-being, contributing to the higher prevalence of depression in females. Recognising the hormonal factors involved in mood disorders is essential for developing effective treatment strategies tailored to women’s specific needs and experiences.

Scan the QR code on page 3 for reference lists. SF

Fracture prevention strategies

Osteoporosis is a skeletal disorder characterised by low bone mass and microarchitectural deterioration, leading to increased bone fragility and fracture risk.1 One in three women and one in five men >50-years will suffer a fragility fracture due to osteoporosis.2

Worldwide, up to 37 million fragility fractures occur annually in individuals >55-years, which equate to 70 fractures per minute. 3

Osteoporosis is frequently undiagnosed and undertreated, despite effective antifracture interventions and the potentially deadly consequences of fractures. 4

In a 2021 meta-analysis of 86 studies with >103 million participants, the global prevalence of osteoporosis was 18.3%. Among women, the prevalence was 23.1%, while among men it was 11.7%. Africa had the highest prevalence at 39.5%. 5

Salari et al emphasised that although osteoporosis is not necessarily defined by fractures, the consequence is fractures. 5 The lifetime risk of osteoporotic fractures is between 40%-50% in women and 13%-22% in men, with men facing a higher mortality risk. 6

Fragility fractures, often occurring due to low-energy trauma during routine activities, typically affect the vertebrae (spine), proximal femur (hip), distal forearm (wrist), and proximal humerus. While vertebral fractures are the most common, hip fractures have the most significant impact on mortality and morbidity. Almost 25% of hip fractures are fatal, and many survivors face long-term disability, with up to 30% experiencing loss of independence.4,7

Hawley et al (2022) predicted a substantial increase in hip fracture burden in South Africa, with estimates rising from about 11 000 cases in 2020 to ~26 400 cases by 2050. 8

Clinical or subclinical vertebral fractures increase the risk of subsequent fractures five-fold for vertebral fractures and two to three-fold for fractures at other sites. 4

Salari et al cautioned that vertebral fractures are often overlooked in patients presenting with back pain, leading to delays in diagnosis and appropriate management. 5

Van Oostwaard noted that patients with spinal fractures often remain undiagnosed due to mild or absent symptoms. As a result, only ~25% of spinal fractures are clinically identified. Wrist fractures rank as the third most common type of osteoporotic fracture, comprising up to 18% of all fractures among the elderly.7

Van Oostwaard stressed that recognising and treating the first fragility fracture can reduce the risk of subsequent

fractures by about 50%. Identifying high-risk patients early is crucial.7

Primary prevention strategies involve identifying individuals at risk of the first fracture through comprehensive evaluation and initiating treatment, often in primary healthcare settings.7

To identify patients at risk, bone mineral density (BMD) screening is recommended in women >65- and men >70-years. It is also recommended in younger postmenopausal women between 50- and 64-years, and men between 50- and 69-years with risk factors for osteoporosis. Additionally, BMD testing is recommended for men who have a history of fractures at ≥50-years. 4

Secondary prevention focuses on preventing subsequent fractures in patients with a history of osteoporotic fractures, typically through structured programmes like fracture liaison and orthogeriatric services initiated in hospital settings.7

Treatment

Less than 20% of individuals who sustain a fragility fracture receive therapies to reduce the risk of subsequent fractures within the year following the initial fracture. Treating osteoporosis involves a combination of pharmacotherapy, lifestyle modifications, ensuring adequate intake of calcium and vitamin D, and implementing measures to prevent falls.7

Non-pharmacological measures to prevent osteoporotic fractures are mainly focused on enhancing bone strength and minimising the risk of falls. Non-pharmacological methods to improve bone strength include following a balanced diet, physical weight-bearing and musclestrengthening exercises, limiting alcohol consumption, quitting smoking, and avoiding medications that reduce bone strength. 4

A balanced diet with adequate calcium and vitamin D intake is recommended. The calcium intake recommendations are 1000mg/day for men aged 50- to 70-years and 1200mg/day for women aged ≥51-years, and for men aged ≥71-years. Good dietary sources of calcium include low-fat dairy products, dark greens, fish with bones, fruits, vegetables, and fortified foods. If dietary intake is insufficient, consider calcium supplements. 4

At least 1 in 3 women and 1 in 5 men will suﬀer from an osteoporotic fracture during their lifetime1

1 in 3 hip fracture patients re-fracture at 1 year1

20 % risk of suﬀering a second spine fracture within the year following the ﬁrst one1

28 % of Women and 37 % of Men who suﬀer a hip fracture, will DIE within the following year1

Reduced fracture rates are observed only in patients with proper persistence and compliance (adherence > 80 %) on long-term BP therapy2

Alendronate sodium equivalent to alendronic acid 70 mg tablets.

Osteoporosis

It is recommended to have a daily intake of 800 to 1000 units of vitamin D for adults aged ≥50-years. Monitor 25-hydroxyvitamin D levels to maintain sufficiency (≥30ng/ ml but below ≤50ng/ml). Vitamin D sources include fortified milk, breakfast cereals, fish, and cod liver oil. In cases where an individual aged ≥50-years and cannot achieve sufficient vitamin D levels through diet, it is recommended to supplement with 800-1000 units/day. Higher doses may be necessary for adults, especially those with malabsorption.4

Pharmacological treatments for osteoporosis include antiresorptive agents, also known as anticatabolics aimed at improving bone strength and anabolics aimed at reducing fracture risk.7

Antiresorptive agents include:7

_ Bisphosphonates

_ Oestrogen-related therapy, selective estrogen receptor modulator

_ RANK ligand inhibitor

_ Denosumab, a monoclonal antibody.

Stimulators of bone reformation:

_ Parathyroid hormone (PTH) analogues.

Consider initiating pharmacologic treatment in postmenopausal women and men aged ≥50-years who meet the following criteria:4

For primary fracture prevention:

_ A T-score of ≤ -2.5 at the femoral neck (FN), total hip (TH), lumbar spine (LS), or 33% radius (with some data uncertainty) as measured by DXA

_ Low bone mass (osteopaenia with a T-score between -1.0 and -2.5) at the FN or TH, combined with a 10-year hip fracture risk ≥ 3% or a 10-year major osteoporosisrelated fracture risk ≥ 20% based on the FRAX® model.

For secondary fracture prevention:

_ Fracture of the hip or vertebra regardless of BMD

_ Fracture of the proximal humerus, pelvis, or distal forearm in individuals with low bone mass (osteopaenia with a T-score between -1.0 and -2.5). The decision to treat should be individualised for those with a fracture of the proximal humerus, pelvis, or distal forearm who do not have osteopaenia or low BMD.

Teriparatide for patients at high or very high risk of fracture

Teriparatide, a recombinant fragment of PTH, is recommended for patients at high risk of fractures, including those with severe osteoporosis, multiple fractures, or intolerance to other therapies. 4 It is also approved for the treatment of osteoporosis associated with sustained systemic glucocorticoid therapy. 4

Studies show that teriparatide significantly reduces the risk of vertebral fractures by 65%-77% and non-vertebral fractures by 35%-53% over an average treatment period of 18-months. 4

In a comparative trial by Kendler et al (2018), 680 participants (post-menopausal women with severe osteoporosis) were enrolled and randomly assigned to receive either daily teriparatide injections plus weekly oral placebo or weekly risedronate tablets plus daily placebo injections over 24-months. The primary outcome was new radiographic vertebral fractures. Teriparatide showed lower rates of new vertebral fractures (5.4% vs 12% in the risedronate group), clinical fractures (4.8% vs 9.8%), and non-vertebral fragility fractures (4% vs 6.1%). The risk of vertebral fractures was 56% lower, and the risk reduction was statistically significant (p < 0.0001).9

A 10-year follow-up study was conducted after administering teriparatide 20μg subcutaneously daily for an average of 18-months in 40 women with osteoporosis and vertebral compression, with a mean age of 69 years. As controls, 25 women with osteoporosis and a mean age of 60 years, who were part of a randomised, doubleblind, placebo-controlled growth hormone trial receiving daily subcutaneous injections for 18-months, were used. Furthermore, 233 women of similar age from a random population sample also served as controls and were followed in parallel. Women treated with teriparatide experienced a decrease in fractures from 100% to 35%, similar to the levels observed in the population sample.10

A 2023 cross-sectional study aimed to assess the effects of teriparatide on BMD and bone markers in real-life clinical settings compared to clinical trials. Post-menopausal women treated with teriparatide for at least 12 months were studied. Results showed a significant increase in bone turnover markers after six months of teriparatide treatment. Lumbar spine BMD increased significantly after six months, reaching its peak at 24 months. Similar increases were observed in femoral neck and total hip BMD. The study concluded that real-life results matched those of randomised clinical trials, and teriparatide increased BMD regardless of previous antiresorptive medication use.11

Conclusion

Teriparatide is pivotal in the management of osteoporosis, offering significant benefits in enhancing BMD and reducing fracture incidence, both vertebral and non-vertebral. Its effectiveness in clinical trials and real-world settings underscores its importance in improving patient outcomes. Scan the QR code on page 3 for reference lists. SF

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The Cipla Foundation strives to make a tangible diﬀerence in people’s lives. Our mission is to make a sustainable impact on people and communities in need.

The thinking and ethos that ﬂows from the Global Sustainable Development Goals through to the South African National Development Plan 2030 ﬁnds expression on the streets of South Africa in our four core Cipla Foundation initiatives.

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