While precautions have been taken to ensure the accuracy of its contents and information given to readers, neither the editor, publisher, or its agents can accept responsibility for damages or injury which may arise therefrom. All rights reserved.
The 19th World Congress on Menopause, held in Melbourne, Australia, in October 2024, gathered global leaders in women’s health to discuss transformative approaches to menopause care. A contingent of South Africa’s leading gynaecologists attended, bringing home critical insights to shape patient care.
Akey focus was osteoporosis, a silent yet significant threat to postmenopausal women.
Declines in bone mineral density, driven by hormonal changes, increase fracture risk and impair quality of life.
Early menopause exacerbates this risk, highlighting the need for timely intervention.
Effective management strategies combine early diagnosis, lifestyle adjustments, and treatments like bisphosphonates, and menopausal hormone therapy (MHT). Experts emphasised personalised approaches, with fracture risk models like FRAX guiding tailored interventions.
Transdermal oestrogen emerged as a preferred MHT option for its safety and efficacy. By bypassing liver metabolism, it reduces risks of venous thromboembolism, cardiovascular complications, and other side effects.
This makes it ideal for women with obesity or preexisting CV risk factors, improving adherence and outcomes. Conversely, compounded MHT (CMHT) was strongly cautioned against due to inconsistent quality and safety concerns. Experts stressed the importance of regulated, body-identical hormones in ensuring optimal patient outcomes.
Peri-menopausal depression (PMD) also took centre stage. Unlike major depressive disorder, PMD stems from hormonal fluctuations, with symptoms like anxiety and brain fog resisting traditional treatments.
MHT offers a holistic solution, stabilising oestrogen levels and improving mood and cognitive function. Individualised care remains essential to balance benefits with potential risks.
This guide encapsulates the congress’s highlights, reaffirming the commitment to advancing menopause care and enhancing women’s health globally.
Article reviewed by Dr Tobie de Villiers
Long-term strategies for osteoporosis care
Bone conundrums
Osteoporosis is a common, chronic condition characterised by decrease of bone strength and an increased risk of fractures –particularly in older adults and post-menopausal women. In post-menopausal women, the risk of fracture is largely driven by menopause-related hormonal changes, which significantly contribute to a decline in BMD.
Summary
Osteoporosis, a chronic condition marked by decreased bone strength and increased fracture risk, is often underdiagnosed, particularly in postmenopausal women whose bone mineral density (BMD) declines due to hormonal changes. Effective management involves early diagnosis, lifestyle modifications, and pharmacological treatments such as bisphosphonates, denosumab, and menopausal hormone therapy (MHT). Early menopause exacerbates bone loss, making intervention critical to prevent fractures and improve outcomes. Comprehensive, individualised care is essential, particularly for high-risk patients, to preserve mobility and quality of life (QoL). MHT uniquely enhances bone microarchitecture, offering dual benefits in early menopause, while long-term strategies are key to mitigating osteoporosis’s broader impact.
Despite its high prevalence, osteoporosis is often under-recognised, leading to delayed diagnoses and missed opportunities for intervention, noted Prof Eugene McCloskey, head of the Department of Adult Bone Disease at the University of Sheffield (United Kingdom) and one of the world’s foremost osteoporosis experts.
Long-term management of osteoporosis is essential
Effective long-term management of osteoporosis is essential to reduce fracture risk and improve quality of life, he stressed. Although osteoporosis is commonly associated with fractures, the
disease goes beyond bone health, affecting mobility, independence, and QoL, he added.
He also emphasised that once a fracture occurs, the risk of subsequent fractures significantly increases, particularly within the first few years. As such, early intervention is key to preventing further fractures and improving patient outcomes.
Reducing fracture risk
Effective management of osteoporosis centers around reducing fracture risk through a combination of lifestyle changes and pharmacological treatments. Lifestyle interventions, such as a calcium-rich diet, regular weight-bearing exercises, maintaining a healthy body mass index, smoking cessation and moderating alcohol intake, are vital for maintaining BMD, and overall health. However, for individuals at high risk of fractures, pharmacological treatments may be necessary.
Preventing further bone loss
The treatment of osteoporosis involves various pharmacological treatments aimed at preventing further bone loss. Bisphosphonates are commonly used to inhibit bone resorption, thereby preserving BMD.
Other inhibitors of bone resorption include denosumab, MHT, and anabolic treatments, which stimulate bone formation to improve skeletal health such as teriparatide.
Osteoporosis requires continuous treatment
Osteoporosis is a chronic condition that requires continuous management. An individualised, comprehensive approach is needed, especially for patients with a history of fractures or those at higher risk. Early diagnosis and tailored interventions, based on individual risk factors, can greatly reduce the disease’s impact on affected individuals’ lives.
Early menopause: A window of opportunity for bone health
Dr Tobie de Villiers, a consultant gynaecologist, and past-president of the International Menopause Society, stressed the critical importance of early intervention in the prevention of osteoporosis.
He explained that early menopause accelerates bone loss due to the rapid decline in oestrogen levels, which increases osteoclastic activity and enhances bone
resorption. This accelerated bone loss typically occurs one to two years before the final menstrual period and can continue for up to four years afterward.
The resulting loss of BMD, particularly in the lumbar spine and femoral neck, can reach up to 10%, making early intervention crucial. The damage is not limited to loss of BMD but also deterioration of bone microarchitectural quality.
Early menopause represents a significant risk factor for bone loss
Reducing fracture risk in osteoporosis requires lifestyle changes like exercise and diet, often paired with pharmacological treatments
Osteoporosis screening typically starts after the age of 65, but early menopause represents a significant risk factor for accelerated bone loss which is missed if BMD is only measured at 65. Women experiencing early menopause should be monitored closely for osteoporosis, as they may experience bone deterioration long before reaching the typical screening age.
Pharmacological interventions
Bisphosphonates, raloxifene, denosumab and MHT, have all been shown to prevent the bone loss associated with menopause. These medications work by inhibiting osteoclast activity, helping to slow bone resorption.
MHT offers additional an additional benefit, Dr de Villiers noted that MHT in improves bone microarchitecture, potentially reversing some of the structural deterioration seen in osteoporosis. This dual effect of MHT makes it an important treatment option for women in early menopause.
Reference
McCloskey E. Long-term strategies for osteoporosis care. 2024 [Internet]. Available at: https://imsmelbourne2024.com/u/ virtual-congress/ De Villiers T. Early menopause: A window of opportunity for bone health 2024 [Internet]. Available at: https://imsmelbourne2024. com/u/virtual-congress/ SF
Simplifying therapy. Strengthening bones. 1-4
risk of vertebral fractures vs. weekly bisphosphonates4
• Sustained low clinical fracture rate over 5 years of treatment 6
• Maintained lumbar spine BMD with further gradual increases up to 5 years2
• Well-tolerated with a proven 5-year safety profile2
• Increased patient persistence and preference may contribute to improved fracture protection*3,7,8
www.adcockingramrx.co.za
Article reviewed by Dr Tobie de Villiers
Osteoporosis:
When and how?
Osteoporosis treatment should be guided not only by BMD values but also by the presence of other risk factors for fracture. This is commonly done using an integrated fracture risk assessment model such as FRAX, to predict the future probability of fracture.
Summary
Osteoporosis management extends beyond bone mineral density (BMD) thresholds to incorporate fracture risk models like FRAX. Prof Eugene McCloskey emphasises integrating clinical factors and future fracture risk in treatment decisions, enhancing precision in patient care. Menopausal hormone therapy (MHT), bisphosphonates, and newer anabolic agents offer tailored options. MHT supports bone health during early menopause, while anabolic treatments show promise for high-risk patients, followed by anti-resorptives for maintenance. Prof Bronwyn Stuckey and Dr Santiago Palacios highlight combining treatments based on patient profiles, advancing osteoporosis care with innovative therapies targeting bone metabolism and remodelling.
Intervention thresholds are more complicated and should be calculated using local recommendations. Treatment options include agents inhibiting bone
resorption (bisphosphonates, MHT and denosumab) and anabolic agents.
Diagnosis and intervention thresholds
Although the diagnosis of osteoporosis is based on BMD T-scores intervention thresholds should also take into account future risk of fracture. Focusing exclusively on BMD may miss individuals at high fracture risk who do not meet the osteoporosis threshold T-score of -2.5, stressed Prof McCloskey.
For this reason, other risk factors, such as clinical history, age, and previous fractures, should also be considered when predicting fracture risk. Tools like the FRAX calculator, which incorporates BMD and additional clinical risk factors, can help determine fracture probabilities and guide treatment decisions more accurately.
Traditionally, treatment decisions were based on a simple ‘should I treat or not?’ approach, but with newer treatments available, the question now expands to ‘which treatment should be used based on the patient’s risk profile?’ Some guidelines use a more comprehensive risk factor approach, considering both BMD and clinical history.
Prof McCloskey highlighted that while the T-score remains important, relying solely on it may result in some individuals being excluded from treatment despite having a high fracture risk due to other factors. Tools like
FRAX provide a more precise risk assessment, allowing healthcare providers to identify those at risk, even if they do not meet the strict BMD criteria for osteoporosis.
Pharmacological treatment for fracture prevention: What is the role of MHT?
According to Prof Stuckey, an endocrinologist based at University of Western Australia, MHT is essential for maintaining BMD – especially when started early in menopause.
MHT involves administering oestrogen alone or combined with a progestin in the presence of a uterus, to alleviate menopausal symptoms and prevent bone loss. Oestrogen plays a multi-faceted role in bone health, reducing bone resorption by decreasing receptor activator of nuclear factor Kappa-B (RANK) ligand levels and increasing osteoprotegerin production, which in turn inhibits osteoclast activity.
Additionally, oestrogen enhances bone formation by promoting osteoblast differentiation and reducing apoptosis. Evidence from the Women’s Health Initiative study (WHI) indicates that conjugated equine estrogen alone or combined with medroxyprogesterone acetate significantly reduces all osteoporosis-related fractures, even in women not selected on grounds of high risk of fracture.
WHI also reported a marginal increase in breast cancer risk only in the combined therapy arm. The risk of breast cancer with MHT remains low, particularly when balanced against its benefits in fracture prevention, stressed Prof Stuckey.
When comparing MHT with bisphosphonates and denosumab, MHT offers comprehensive benefits by affecting both bone resorption and formation, without the side effects seen in prolonged bisphosphonate use.
For optimal osteoporosis management, the choice between MHT and bisphosphonates depends on individual risk factors and preferences. MHT is often preferred in early menopause for its overall health benefits, while bisphosphonates or denosumab are preferred for older women or those contraindicated for MHT.
Anabolic treatment fracture prevention: New perspectives
Anabolic treatments have become an essential part
of managing osteoporosis, particularly in patients at very high risk of fractures. These bone-forming agents work by stimulating bone formation, improving BMD, and enhancing the microarchitecture of both trabecular and cortical bone, according to Dr Palacois, director of the Palacios Institute of Health and Women’s Medicine (Spain).
For patients at very high fracture risk, starting with bone-forming agents is a key strategy. After initiating anabolic therapy, patients typically transition to antiresorptive drugs after 18-24 months to maintain the gains in bone density and reduce the risk of further fractures. The action of anabolics may be impeded if it follows bisphosphonates.
Anabolic treatments are particularly beneficial in patients at very high risk of fractures, including those with a T-score of <-3.0, a FRAX predicted probability over the next 10 years of >20% (any major osteoporotic fracture) or >3% (hip fracture), a severe vertebral fracture or several moderate fractures
By stimulating bone formation, these agents not only increase BMD but also improve bone quality, particularly in the trabecular and cortical bone regions. This dual action helps to reduce fracture risk, especially for vertebral fractures.
Bisphosphonates and denosumab in osteoporosis treatment
Bisphosphonates bind to bone surfaces, inducing osteoclast apoptosis and thereby decreasing bone breakdown. These agents are effective in reducing fracture risks and have a prolonged presence in bone.
Bisphosphonates remain a cornerstone of osteoporosis treatment, especially for patients at high risk of fracture and for those at very high risk of fracture as maintenance treatment after anabolic treatment, said Dr Palacois.
Bisphosphonates inhibit bone resorption by binding to hydroxyapatite in bone and preventing the activity of osteoclasts, the cells responsible for breaking down bone tissue.
This results in an overall reduction in bone loss and a significant decrease in fracture risk.
When started after anabolic agents, bisphosphonates help to maintain the improvements in BMD achieved by anabolic therapy, further reducing the risk of fractures,
Key messages
1. Comprehensive risk assessment is crucial for osteoporosis diagnosis and treatment
While BMD T-scores are essential for diagnosing osteoporosis, they should not be the sole determinant for treatment. Tools like FRAX, which incorporate additional clinical risk factors, provide a more precise prediction of fracture risk, ensuring high-risk individuals are not overlooked despite normal T-scores.
2. Personalised treatment decisions are necessary
Treatment should not only focus on whether to intervene but also on selecting the most appropriate therapy based on individual risk profiles. This shift from a binary approach ensures optimal management tailored to each patient’s needs.
3. MHT as a first-line treatment in early menopause
MHT plays a critical role in preventing bone loss and reducing fracture risk, especially when initiated early. It influences both bone resorption and formation, making it a comprehensive option for maintaining bone health.
4. MHT offers unique advantages over other treatments
MHT provides benefits beyond bone density, including broader health effects, and has a low risk of breast cancer when appropriately used. It is often preferred over bisphosphonates in early menopause for its multifaceted impact.
5. Anabolic agents for very high fracture risk
Anabolic treatments stimulate bone formation, significantly improving BMD and bone quality in patients at very high fracture risk. These therapies are often initiated before transitioning to antiresorptive drugs to maintain gains.
6. Strategic use of bisphosphonates and denosumab
Bisphosphonates are effective maintenance therapies post-anabolic treatment, with considerations for drug holidays to prevent side effects. Denosumab, while highly effective for long-term BMD improvement, requires careful management to prevent rapid bone loss upon discontinuation.
particularly in the long term. Osteonecrosis of the jaw is a rare complication seldom seen at the dosages used for fracture prevention.
Atypical femur fractures can be prevented by avoiding long term continuous exposure to bisphosphonates. Drug holidays of two- to five-years should be considered after three yearly intravenous treatments or after five-years of oral therapy. However, this strategy is not feasible with denosumab, a monoclonal antibody that inhibits RANK ligand – a key regulator of osteoclast activity.
Discontinuation of denosumab can result in rapid bone loss and increased fracture risk as denosumab is blood borne and does not bind to bone. Denosumab, unlike bisphosphonates, is not excreted by the kidneys and can be used in patients with impaired renal function.
Bisphosphonates cause an initial increase in BMD in the first three-years after which it only maintains BMD. Denosumab continues to increase BMD for at least 10-years. On attaining target BMD whilst on denosumab therapy, this should be followed by a bisphosphonate.
New perspectives
As research continues, new anabolic agents are being developed to further improve osteoporosis treatment. These include drugs targeting sclerostin and other proteins involved in bone metabolism, as well as potential therapies like mesenchymal stem cell infusions, which have shown promise in increasing both trabecular and cortical bone.
Other emerging therapies focus on inhibiting the key proteins involved in bone remodeling. For example, clinical trials have shown that inhibitors of certain proteins, such as DKK1, can increase BMD and reduce fracture risk, potentially offering a new avenue for osteoporosis treatment in the coming years.
References
McCloskey E. Diagnosis and intervention thresholds. 2024 [Internet]. Available at: https://imsmelbourne2024.com/u/ virtual-congress/ Stuckey B. Pharmacological treatment for fracture prevention: What is the role of MHT? 2024 [Internet]. Available at: https:// imsmelbourne2024.com/u/virtual-congress/ Palacois S. Anabolic treatment fracture prevention: New perspectives. 2024 [Internet]. Available at: https:// imsmelbourne2024.com/u/virtual-congress/ SF
Summary
Should MHT be first-line for treating peri-menopausal
depression?
Unlike typical MDD, PMD presents unique challenges and symptoms. Given its hormonal basis, this condition calls for a tailored treatment approach, with MHT emerging as a promising first-line option, stressed Prof Jayashri Kulkarni, director HER Centre Australia and Monash Alfred Psychiatry research Centre.
Peri-menopausal depression (PMD), distinct from major depressive disorder (MDD), is driven by hormonal fluctuations during the menopause transition. Symptoms such as severe anxiety, irritability, and brain fog often resist traditional antidepressants, which address neurotransmitter imbalance but not hormonal shifts. Menopausal hormone therapy (MHT) stabilises oestrogen levels and alleviates mood and cognitive symptoms. By addressing the neuroendocrine underpinnings, MHT offers a holistic solution, though individualised assessment and consideration of risks are essential for optimising outcomes.
Peri-menopause is the transitional period leading up to menopause, characterised by fluctuating levels of oestrogen and other sex hormones. These hormonal changes can profoundly impact mental health, leading to a form of depression distinct from typical MDD. The commonly used psychiatric classifications do not effectively capture the nuances of peri-menopausal depression, according to Prof Kulkarni. For instance, the Diagnostic and Statistical Manual of Mental Disorders classification of mood disorders does not specifically recognise depression related to
peri-menopause, often categorising it under broader, unrelated terms like MDD with peri-partum onset, which does not accurately reflect the hormonal or life-stage factors involved.
The International Classification of Diseases (ICD) system vaguely references menopausal and peri-menopausal disorders, but without specific criteria. The ICD therefore also fails to adequately identify or address the mental health challenges unique to this life stage. This lack of precise classification reflects broader issues in the recognition and treatment of PMD, contributing to its underdiagnosis and under-treatment, explained Prof Kulkarni.
The symptom profile of PMD differs significantly from that of traditional MDD. While classic depression often
Dr Johannes van Waart, director and founder of Wijnland Fertility, Gynaecologist, Obstetrician and Fertility Specialist, past president of The South African Society of Obstetricians and Gynaecologists and Federation of South African Surgeons comments: HT is well established as a safe and effective way to enhance QoL in climacteric patients. Although some risks are known, the effect of HT on hormone related mood changes gives hope to many women affected by this condition. Stabilising hormone levels (and its effects) not only makes good practical sense but is now also supported by scientific evidence. This advantage of HT should be included in the patient doctor discussion when HT is considered as a treatment option in climacteric patients.
Article reviewed by Dr Johannes van Waart
involves persistent sadness, loss of interest, and weight loss, PMD features severe anxiety, panic attacks, irritability, paranoia, and a distinct brain fog affecting memory and concentration. Women may also experience physical symptoms such as weight gain, somatic pains, and sexual dysfunction (eg loss of libido and vaginal dryness). These unique symptoms highlight the biological underpinnings of PMD, which are closely tied to the hormonal shifts occurring during this transition.The severity of PMD can have a profound impact on women’s quality of life (QoL), affecting work performance, relationships, and overall well-being.
Limitations of traditional antidepressants
Traditional antidepressants like selective serotonin reuptake inhibitors (SSRIs) have limited efficacy in treating this type of depression. This is because the core issue lies not in neurotransmitter imbalance alone but in the broader neuroendocrine changes driven by hormonal fluctuations, stressed Prof Kulkarni.
Anti-depressants are less effective for perimenopausal depression, as they do not address the hormonal triggers underlying the condition. Clinical studies show that antidepressants yield only partial relief for peri-menopausal women, with a response rate of ~40%, significantly lower than for typical MDD cases. Furthermore, anti-depressants can exacerbate some peri-menopausal symptoms. Common side effects such as weight gain and loss of libido overlap with and may worsen the symptoms experienced during peri-menopause, making these treatments less appealing for affected women. Additionally, SSRIs may contribute to mood flattening, where patients feel emotionally numb rather than improved, further limiting their effectiveness in this context.
The case for MHT as first-line treatment
MHT involves the administration of oestrogen, often combined with progestin, to alleviate symptoms associated with menopause, including mood disturbances. Oestrogen, a potent neurosteroid, plays a crucial role in the brain’s neurocircuitry and neurochemistry, impacting neurotransmitter systems such as serotonin, dopamine, and glutamate. Fluctuating oestrogen levels during perimenopause can disrupt these systems, leading to mood instability, cognitive changes, and other symptoms of depression. By stabilising oestrogen levels, MHT can address the
root hormonal cause of PMD. Research indicates that MHT can effectively alleviate symptoms of anxiety, mood swings, and cognitive disturbances associated with hormonal fluctuations. Unlike anti-depressants, which only partially address neurotransmitter imbalances, MHT targets the broader hormonal imbalances driving the condition.
Given the unique hormonal basis of PMD, MHT presents a compelling first-line treatment option. As mentioned, unlike anti-depressants, MHT directly targets the hormonal changes driving the condition, offering a more holistic approach to symptom relief. Evidence suggests that oestrogen therapy can stabilise mood, reduce anxiety, and improve cognitive function by modulating neurotransmitter activity and reducing inflammation in the brain.
MHT’s broader impact on neuroendocrine health also supports its use as an initial treatment. Oestrogen enhances neuroplasticity, promotes neurogenesis, and helps maintain healthy neurotransmitter function, making it a suitable option for addressing the complex, multi-faceted nature of peri-menopausal depression. Furthermore, MHT does not carry the same overdose risk as traditional antidepressants, offering a safer profile in patients with severe depressive symptoms or suicidal ideation.
Despite its potential benefits, MHT is not without risks and controversies. Concerns about the long-term safety of MHT, particularly its association with an increased risk of breast cancer, have led to caution in its use. However, recent evidence suggests that the actual risk increase is small, especially when MHT is initiated early in menopause and tailored to the individual’s needs.
The decision to use MHT should be based on a thorough evaluation of the patient’s risk factors, symptoms, and preferences, allowing for a personalised approach to treatment. Another challenge is the lack of standardised diagnostic tools specific to perimenopausal depression. Many studies use traditional depression rating scales that do not capture the unique symptoms of this condition, potentially underestimating the effectiveness of MHT in this population. Developing and utilising specialised assessment tools could improve the accuracy of diagnosis and treatment outcomes.
Reference
Kulkarni J. Should MHT be first-line for treating perimenopausal depression? 2024 [Internet]. Available at: https:// imsmelbourne2024.com/u/virtual-congress/ SF
ADCOCK INGRAM WOMEN’S HEALTH
YOUR PARTNER THROUGH HER MENOPAUSE JOURNEY
From relief of menopausal symptoms and prevention of postmenopausal osteoporosis to the treatment of established osteoporosis to prevent fractures1,2,3,4,5,6,7,8
MENOPAUSE TRANSDERMAL OFFERING OSTEOPOROSIS
For women after hysterectomy.1
50
For woman with an intact uterus.2
Peri-menopause with irregular cycles.9,10
50
For woman with an intact uterus.3
Postmenopausal and bleed-free.9,10
The first once-monthly tablet.6,11
Quarterly injection for postmenopausal osteoporosis.7
Once-yearly infusion.8
For women after hysterectomy.*4
50
For women with an intact uterus.5 Postmenopause and bleed-free.9,10
References: 1. EVOREL®
ESTRADOT® 100: 37/21.8.1/0218. Sandoz South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, 2090. Co. Reg. No. 1946/020671/07. For full prescribing information refer to the professional information approved by the medicines regulatory authority. ESTALIS® 50/140 Transdermal patch. Transdermal patch containing a combination of norethisterone acetate (NETA) and oestradiol (E2) releasing 50 micrograms E2 per day and 140 micrograms NETA per day. Reg. No.: ESTALIS® 50/140: 37/21.8.2/0456. Sandoz South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View, 2090. Co. Reg. No. 1946/020671/07. For full prescribing information refer to the professional information approved by the medicines regulatory authority. BONIVA® 3 mg/3 ml injection. Each pre-filled syringe (3 ml) contains ibandronic acid 3 mg (as
estradiol, formulated as 1,6 mg of estradiol hemihydrate. Reg. No. 30/21.8.1/0207. (boxed) EVOREL® 50 (patch). Each EVOREL® 50 (16 cm2) patch contains 3,10 mg estradiol, formulated as 3,2 mg of estradiol hemihydrate. Reg. No. Z/21.8.1/339. (boxed) EVOREL® 75 (patch). Each EVOREL® 75 (24 cm2) patch contains 4,65 mg estradiol, formulated as 4,8 mg of estradiol hemihydrate. Reg. No. 30/21.8.1/0208. (boxed) EVOREL® 100 (patch). Each EVOREL® 100 (32 cm2) patch contains 6,20 mg estradiol, formulated as 6,4 mg of estradiol hemihydrate. Reg. No. 30/21.8.1/0209. For full prescribing information refer to the professional information approved by the medicines regulatory authority (SAHPRA).
Article reviewed by Dr Johannes van Waart
transdermally? Should oestrogen always be delivered
The answer is unequivocally YES, said Dr Sonia Davison, an endocrinologist with a special interest in women’s health, based at the Jean Hailes Medical Centre in Australia. She added that the argument that oestrogen should always be delivered transdermally is grounded in clinical evidence showing numerous advantages over oral administration, particularly for menopausal women who often seek HT to manage menopausal symptoms.
Summary
Transdermal oestrogen offers significant safety and efficacy benefits over oral administration. By bypassing firstpass liver metabolism, it reduces risks such as venous thromboembolism (VTE), pulmonary embolism (PE), and cardiovascular (CV) complications. This makes it particularly suitable for women living with obesity or pre-existing CV risk factors. Additionally, transdermal delivery ensures stable hormone levels, lower effective doses, and fewer side effects, improving adherence and quality of life (QoL). These advantages highlight its critical role in managing menopausal symptoms and protecting long-term health.
Transdermal oestrogen, absorbed through the skin via patches, gels, or sprays, offers a safer and more effective alternative – especially considering the growing rates of obesity, CV issues, and metabolic disorders in menopausal women. One of the primary benefits of transdermal oestrogen is that it bypasses the
liver’s first-pass metabolism. When oestrogen is taken orally, it must first pass through the gastrointestinal (GI) system and the liver, where it can trigger the production of various proteins and inflammatory markers. This increases the risk of adverse effects such as blood clots –especially in women who are already at high risk due to obesity, sedentary lifestyle, or pre-existing CV conditions.
Dr Johannes van Waart, director and founder of Wijnland Fertility, Gynaecologist, Obstetrician and Fertility Specialist, past president of The South African Society of Obstetricians and Gynaecologists and Federation of South African Surgeons comments: Taking the evidence presented by the article under discussion, the scope of transdermal HT has now expanded. This is especially true in patients with CV and thrombotic risk factors. Although a small number of patients might have skin irritation from the transdermal patches, the advantages of this route of administration have now been wellestablished. When discussing HT with climacteric patients, all relevant risk factors should be considered when deciding on the route of administration. From the available evidence it seems quite clear that transdermal HT is a good frontrunner as a first option.
EVOREL®: Hormone Replacement Therapy (HRT) patch with a complete range:
EVOREL® range gives you the option to meet the needs for pre and postmenopausal women choosing HRT and adopt an individualised approach1-5
• International and local guidelines recommend transdermal HRT as first-line treatment5,8,9,10
• The EVOREL® range displays many additional benefits over and above the relief of VMS symptoms1-4,11,17-21
• Transdermal HRT should be considered in all suitable women4-6,18,21
• Transdermal patches ensure consistent release of the hormone component and control of VMS7,19,20
Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. 2017;177(10):1471-1479. doi: 10.1001/jamainternmed.2017.3877.12. Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, et al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015;12(6):e1001833; discussion e1001833. doi: 10.1371/journal.pmed.1001833.13. Stepan JJ, Hruskova H, Kverka M. Update on Menopausal Hormone Therapy for Fracture Prevention. Curr Osteoporos Rep. 2019;17(6):465-473. doi: 10.1007/s11914-019-00549-3. 14. Abdi F, Mobedi H, Bayat F, et al. The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in Postmenopausal Women: A Meta-analysis. Iran J Pharm Res. 2017;16(1):380-389.15. Palmisano BT, Zhu L, Stafford JM. Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12. 16. Lundström E, Wilczek B, von Palffy Z, et al Mammographic breast density during hormone replacement therapy: effects of continuous combination, unopposed transdermal and low-potency estrogen regimens. Climacteric. 2001;4(1):42-8. doi: 10.1080/cmt.4.1.42.48. 17. Huvinen E, Holopainen E, Heikinheimo O. Norethisterone and its acetate - what’s so special about them? BMJ Sex Reprod Health.
Transdermal oestrogen, on the other hand, is absorbed directly into the bloodstream, avoiding this process and its associated risks.
Reduced Risk of VTE and PE
The evidence strongly supports that transdermal oestrogen has a lower risk of causing VTE compared to oral oestrogen. Studies, such as the Estrogen and Thromboembolism Risk study, have demonstrated a significantly increased risk of VTE in women using oral oestrogen, while transdermal oestrogen users did not show such an increased risk. This is particularly important given the increasing prevalence of obesity, a major risk factor for VTE. For example, in countries like the United States, where obesity rates are soaring, menopausal women are more likely to have predisposing factors for thromboembolic events. The data suggests that transdermal oestrogen may even reduce the risk of PE, a life-threatening condition, making it a safer choice.
Neutral impact on BP and CV health
CV disease (CVD) is a leading cause of mortality among post-menopausal women, particularly those >60-years. Research indicates that transdermal oestrogen has a neutral effect on blood pressure, unlike oral oestrogen, which can exacerbate hypertension. This makes transdermal delivery a preferred option for women at risk of CVD. Furthermore, observational studies suggest a potentially lower risk of stroke with transdermal oestrogen, providing additional CV protection.
Metabolic benefits and stability of hormone levels
Transdermal oestrogen has also been shown to have favourable effects on metabolism. Unlike oral estrogen, which can increase levels of inflammatory markers and impact lipid profiles adversely, transdermal oestrogen tends to have a neutral or even beneficial effect on cholesterol levels and inflammatory markers. The Kronos Early Estrogen Prevention Study, which compared different forms of HT, found that oestradiol patches did not negatively affect cholesterol or inflammatory markers. In fact, they were associated with improved insulin sensitivity and lower blood sugar levels, suggesting a potential benefit for women at risk of metabolic syndrome and type 2 diabetes. The stable absorption of oestrogen through the skin also helps maintain consistent hormone levels, avoiding the
peaks and troughs associated with oral administration. This stability can reduce the occurrence of side effects and provide more effective symptom relief, particularly for vasomotor symptoms like hot flashes and night sweats.
Lower doses with fewer side effects
Transdermal oestrogen requires a lower effective dose than oral oestrogen to achieve the same therapeutic effects. This is due to its direct absorption into the bloodstream, which allows it to act more efficiently without undergoing extensive liver metabolism. As a result, transdermal delivery minimises the risk of side effects commonly associated with higher doses of oral oestrogen, such as GI discomfort and elevated liver enzymes. Lower doses also help reduce the risk of breast tenderness and other side effects that may discourage women from continuing HT.
Improved safety profile for older women
As life expectancy increases, more women are seeking HT well into their 60s and beyond. For older women, the risks associated with oral oestrogen are particularly concerning due to the increased likelihood of pre-existing conditions such as obesity, hypertension, and diabetes.
Transdermal oestrogen is considered safer for this demographic because it does not raise the levels of coagulation factors or inflammatory markers as oral oestrogen does. This is crucial for mitigating the risks of stroke, heart attack, and other CV events in older women.
Enhanced QoL
Women today are more informed about menopause and HT, partly due to increasing awareness from media, podcasts, and healthcare discussions. Many seek HT to improve their QoL by alleviating symptoms like hot flashes, night sweats, mood swings, and sleep disturbances.
Transdermal oestrogen has been shown to improve sleep quality and may also enhance libido without affecting sex hormone-binding globulin levels, potentially increasing bioavailable testosterone. This can lead to better sexual health and overall well-being, factors that are important for many women as they navigate midlife transitions.
Reference
Davison S. 2024. Should estrogen always be delivered transdermally? [Internet]. Available at: https://imsmelbourne2024.com/u/virtualcongress/ SF
Fact or fiction?
MHT is a well-established and evidence-based treatment for alleviating the symptoms of menopause and improving the quality of life for women entering midlife. However, the increasing popularity of CMHT has led to significant concern among healthcare professionals due to its lack of regulation, consistency, and scientific validation, said Dr de Villiers.
Summary
Compounded menopausal hormone therapy (CMHT) poses significant risks due to its lack of regulation, quality control, and scientific validation, according to Dr Tobie de Villiers. Unlike regulated MHT, CMHT formulations vary and may lead to inconsistent dosing or harmful effects. Dr Nicole Jaff emphasised that regulated MHT also uses body-identical hormones, rigorously tested for safety and efficacy. The South African Menopause Society (SAMS) advocates for regulated therapies, citing their proven safety and individualisation options, and warns against the unverified claims of compounded treatments. Education and evidence-based guidance are critical for ensuring optimal patient outcomes.
SAMS has issued a clear advisory urging healthcare providers to avoid compounded therapies and prioritise regulated MHT, which has undergone rigorous testing and evaluation for safety and efficacy. SAMS highlights that using regulated, governmentapproved therapies is a safer and more ethical choice, given the potential risks and uncertainties associated with CMHT.
Dr Jaff, honourary lecturer in the Division of Chemical Pathology at the University of the Witwatersrand, addressed one of the most persistent misconceptions surrounding the term ‘bioidentical’. The perception that compounded products are safer or more natural because they contain ‘bioidentical hormones’ is misleading. It is important to note that regulated MHT also uses body-identical hormones that are chemically identical to those produced by the human
body. The difference lies in the regulation – regulated MHT is rigorously tested for safety and efficacy, while compounded products are not. This distinction is vital because many patients are drawn to compounded therapies based on marketing claims rather than scientific evidence, leaving them unaware of the potential risks they may face.
Risks and responsibilities in CMHT use
One of the key issues with compounded hormone therapies is the lack of consistency in their formulation. Since these products are typically custom-made in compounding pharmacies, there is no guarantee that each batch will contain the same dosage or meet quality standards. This variability can lead to underdosing, overdosing, or exposure to contaminants, which significantly increases the risk of adverse effects. Additionally, compounded therapies are not subjected to the rigorous regulatory oversight required for licensed pharmaceutical products, making it nearly impossible to ensure their safety and efficacy. Dr de Villiers emphasised the ethical obligations of healthcare providers
Dr Miems Kleynhans, gynaecologist and obstetrician in private practice, Pretoria, comments: In South Africa and globally, there appears to be no universally established standard range of testosterone levels for women. Without a clear consensus or published guidelines, it is challenging to define accurate levels or approach testosterone treatment for women. Compounding healthcare practitioners often rely on blood tests to monitor testosterone levels every six months, adjusting treatment accordingly. However, this process can be expensive, time-consuming for patients, and may not consider a holistic treatment approach. In contrast, obstetricians and gynaecologists focus on holistic care, using registered, tested, and standardised medications and dosages. This ensures effective treatment not only of testosterone but also of oestrogen and progesterone levels.
Article reviewed by Dr Tobie de Villiers
who choose to prescribe compounded therapies. “If you are going to prescribe compounded therapies, you have an ethical obligation to inspect the compounding facility and ensure that the process is conducted responsibly. Even then, you, as the prescriber, are ultimately responsible for the safety and efficacy of the treatment,” he explained. This responsibility extends to diligent monitoring of patients through serial blood tests, ultrasounds, or other diagnostic measures to detect potential complications such as endometrial hyperplasia, especially when compounded progesterone or testosterone is included in the treatment. Dr de Villiers also raised a critical concern about the lack of clinical evidence supporting CMHT. “You cannot rely on anecdotal experience or nonplacebo-controlled trials with 20 or 30 patients to validate safety or efficacy. Robust peer reviewed evidence published in respectable journals, based on randomised placebocontrolled trials of significant numbers, is necessary to ensure that treatments work and are safe for patients,” he asserted. Without such evidence, prescribers are operating in a highrisk space, both ethically and legally. The absence of reliable non-peer reviewed clinical trials for compounded therapies not only limits the ability to predict their effectiveness but also increases the likelihood of harm to patients.
Legal and insurance implications
The use of compounded therapies also poses significant legal risks for practitioners. Since CMHT is not recognised as a standard treatment within the regulatory framework, complications arising from its use can lead to lawsuits or malpractice claims. Most malpractice insurers do not provide coverage for unregulated therapies, leaving practitioners vulnerable to legal and financial repercussions. Furthermore, practitioners dispensing CMHT without being a licensed dispenser may inadvertently contravene laws related to the dispensing of medications. In South Africa, it is illegal for prescribers to receive kickbacks for prescribing any medication compounded. Dr de Villiers warned against engaging in such practices, stating, ‘engaging in illegal activities, such as receiving financial incentives for prescribing compounded products, not only compromises professional integrity but also risks severe legal consequences. Prescribers must remain within the ethical and regulatory guidelines to protect their patients and their practice’.
Evidence-based practice: A safer path
SAMS strongly advocates for the use of regulated MHT as
the gold standard for managing menopausal symptoms. Regulated therapies include body-identical hormones that have been thoroughly tested for safety, efficacy, and quality. Transdermal oestrogen, in particular, is recommended as a first-line treatment by SAMS and global menopause societies due to its lower risk of VTE and stroke compared to oral formulations. These therapies offer a range of delivery methods, including patches, gels, and sprays, allowing for individualised treatment plans tailored to each patient’s unique needs and preferences. SAMS also underscores the importance of evidence-based practice in ensuring optimal patient outcomes: The individualised approach supported by regulated MHT ensures safe, effective, and scientifically validated treatments. CMHT, on the other hand, offers no such assurances, posing unnecessary risks to patients.
Patient education and awareness
A crucial component of promoting regulated MHT is patient education. Many women are drawn to CMHT because of its marketing appeal, often believing it to be a more natural or customised option. Healthcare providers play a vital role in dispelling these myths and providing clear, evidence-based information about the benefits and risks of different treatment options. This involves open and honest communication with patients, addressing their concerns, and guiding them toward safe and effective therapies. It is our responsibility as healthcare providers to ensure that they make informed decisions based on facts, not marketing claims or pseudoscience, he stressed. Dr de Villiers aptly summarised: The science is clear – regulated MHT is the gold standard. Anything less compromises the trust patients place in us as healthcare providers.
References
de Villiers T. Using CBHT in clinical practice: Safety and medicolegal challenges and issues. Presentation at the 19th World Congress on Menopause. 19-22 October 2024.
Jaff N. SAMS guidelines. Presentation at the 19th World Congress on Menopause. 19-22 October 2024.
Jaffe NG, de Villiers T, and members of the SAMS Advisory Group on Compounded (Bio identical) Menopausal Therapy Group. The South African Menopause Society (SAMS) Statement on Compounded (Bioidentical) Menopausal Hormone Therapy. 2023 [Internet]. Available at: https://www.menopause.co.za/wp-content/ uploads/2024/02/SAMS-CMHT-guidelines-final-October-2023.pdf SF
Blossom with inner confidence
Restore health and vibrancy
Fluomizin®: A novel 6-day vaginal tablet for Bacterial Vaginosis (BV)
- Quinoline derivative: broad-spectrum antiinfective and antiseptic for BV 1,2
- Ra pid bactericidal action: relieves symptoms within 24 to 72 hours 1
Empower women to thrive with vitality now!
- Clinical cure rate of 81,5 % within 7 days* 3
- May be used during pregnancy and lactation if clinically needed #1
- No observed mechanism of acquired resistance to-date 1
BV - bacterial vaginosis *vs clindamycin 2 % vaginal cream3 #Fluomizin® should only be used in pregnancy if clearly needed and can be used during lactation if clinically needed.1
References: 1. Fluomizin® approved professional information, 22 February 2022. 2. Raba G, Durkech A, Malík T, et al. Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(5):e248661. 3. Weissenbacher ER, Donders G, Unzeitig V, et al. A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety. Gynecol Obstet Invest. 2012;73:8-15.
S2 Fluomizin® vaginal tablets. Each vaginal tablet contains 10 mg dequalinium chloride. Reg. No.: 55/18.6/0091. For full prescribing information, refer to the Professional Information approved by SAHPRA. February 2022. Adcock Ingram Limited. Co. Reg. No.: 1949/034385/06. Private Bag X69, Bryanston, 2021. Customer Care: 0860 ADCOCK/232625. www.adcock.com 20.01.20251000000936 January 2025.
