Women’s Health Focus: Polycystic Ovary Syndrome

Polycystic Ovary Syndrome

Written by Dr David Crosby, and Dr Laurentina Schaler, National Maternity Hospital, Dublin

Introduction

Polycystic Ovary Syndrome, or PCOS, is the most common endocrinopathy in women of reproductive age. There can often be a delay in definitive diagnosis due to significant variation in phenotypic presentation. The incidence of PCOS in women of reproductive age is estimated to be between 8 and 13% depending on the population studied. The prevalence in Ireland is 128 per 100,000 women of reproductive age. There is marked variation across Europe, with a prevalence ranging from 34 to 461 in 100,000 women of reproductive age in recently published data1. This variation can be explained by the differences in diagnostic criteria used, the heterogenous nature of the condition and the difference in the number of cases diagnosed in a region. Additionally, certain ethnic groups, including South Asian and Australian Aboriginal populations have a higher incidence of PCOS2 . Although there have been no definitive monogenic causes of PCOS identified to date, it is hypothesised that PCOS may be polygenic in nature, with almost 50% of female first degree relatives of women with PCOS also affected3 .

Diagnosis

The Rotterdam Criteria, defined by the European Society of Human Reproduction and Embryology (ESHRE) and the American Society

Table 1: Rotterdam Criteria (2003) for diagnosis of PCOS* 1. Ovulatory dysfunction 2. Polycystic ovaries on ultrasound (≥12 follicles 29mm per ovary and/or a volume >10ml)** 3. Clinical or biochemical hyperandrogenism

for Reproductive Medicine (ASRM) in 2003, continue to be widely utilised internationally for the diagnosis of PCOS in women of reproductive age. A minimum of two criteria are required to make the diagnosis, after the exclusion of other aetiologies (Table 1). These aetiologies include thyroid disease, hyperprolactinemia, Cushing syndrome, androgen secreting tumours or congenital adrenal hyperplasia. It has been suggested that the diagnosis of PCOS should be approached with caution during puberty as symptoms, which are often transitional during this time, can be mistaken for PCOS and in some cases lead to an overdiagnosis. As a result, it has been recommended that ultrasonographic assessment should not be included in the diagnostic criteria for up to eight years following menarche. Rather, adolescents with symptoms and signs suggestive of PCOS should be followed up and reassessed to establish progression of symptoms before making a definitive diagnosis4 .

Clinical presentation and management

Common clinical presentations of PCOS are outlined in Table 2. Management of patients with PCOS is complex and requires a multidisciplinary approach involving gynaecology, endocrinology, reproductive medicine, dermatology, dieticians, psychology, nursing and other allied healthcare professionals. Management of PCOS can adopt a conservative, medical or surgical approach based on the presentation and the patient’s wishes. Lifestyle modifications, including regular physical exercise and dietary optimisation, form the basis of the initial management and can help achieve optimal body mass index (BMI), regulate hormonal imbalances, and improve quality of life5-7. Counselling can play an extremely important role in the management of women with PCOS. Other conservative measures include cosmetic treatments for hirsutism. Hormonal treatment with a combined oral contraceptive pill (COCP) is recommended to regulate hormonal imbalances and thus regulate menstrual cycles and improve hirsutism. When commencing hormonal therapy, phenotypic features of PCOS, which may be a relative or absolute contraindication to treatment with these modalities, should be taken into consideration. Some international guidelines recommend that in cases where lifestyle and the COCP have failed to achieve an adequate response or in women with high risk of metabolic disease, consideration can be given to the addition of Metformin4. However, there is conflicting evidence that the use of Metformin in PCOS confers any long term benefit8 . The negative effects on the quality of life for women who suffer with PCOS can often be underestimated. Symptoms

*A minimum of 2 out of 3 criteria are required for a diagnosis of PCOS *A minimum of 2 out of 3 criteria are required for a following the exclusion of phenotypically similar androgen excess disorders diagnosis of PCOS following the exclusion of phenotypically similar androgen excess disorders such as such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction, and hyperprolactinemia ** Using transvaginal ultrasound transducers with a frequency bandwidth of ≥ 8MHz, the threshold congenital adrenal hyperplasia, androgen-secreting for polycystic ovarian morphology should be on either ovary, a follicle number tumours, Cushing syndrome, thyroid dysfunction, and per ovary of ≥20 and/or an ovarian volume ≥ 10ml, ensuring no corpora lutea, hyperprolactinemiacysts or dominant follicles are present ** Using transvaginal ultrasound transducers with a OCTOBER - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE frequency bandwidth of ≥ 8MHz, the threshold for polycystic ovarian morphology should be on either ovary, a follicle number per ovary of ≥20 and/or an ovarian volume

Table 2: Common clinical presentations of PCOS • Acne • Alopecia • Hirsutism

• Infertility • Irregular menstrual cycles • Increased body mass index

Symptoms & Management

such as hirsutism, obesity and acne can lead to unnecessary embarrassment and suffering and these should be addressed and managed, where possible. Healthcare professionals must be cognisant of the symptoms of anxiety and depression that women with PCOS may present with and where needed, onward referral for further management should be employed9 .

PCOS and infertility

PCOS is found to be the cause of anovulatory cycles in 80-90% of women with menstrual irregularities and is also a common diagnosis seen in approximately a third of couples attending fertility clinics3. Once again, a multimodal approach is necessary, including lifestyle and diet adjustments for those with higher body mass indices, possibly followed by ovulation induction once other causes of infertility have been excluded. Prior to embarking on fertility treatment in women with PCOS, optimisation of health should be achieved. Women should be advised to take folic acid at a dose of 400mcg daily. In women who are obese (BMI ≥ 30kg/m2), 5mg of folic acid supplementation should be recommended daily. A comprehensive infertility workup should be performed prior to fertility treatment. Investigations to assess ovarian reserve, confirm tubal patency and assess semen analysis if applicable should also be considered prior to fertility treatment to guide the most appropriate individualised management. One management approach is ovulation induction. This can be achieved through oral agents, including selective oestrogen receptor modulators or aromatase inhibitors, or subcutaneous gonadotropins. Initially, all cycles of ovulation induction should be monitored with ultrasonographic follicular tracking. Women with polycystic ovaries are at a higher risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy, and therefore may require even closer monitoring during ovulation induction. If ovulation induction treatment is unsuccessful, a second line approach is laparoscopic ovarian drilling or puncture. Women with PCOS may have ovaries with a thick outer layer. Ovarian drilling works by breaking through the thick outer surface and lowering the amount of testosterone made by the ovaries. This procedure can result in ovulation in up to 50% of women that were unresponsive to initial therapy. Body mass index can also affect ovarian function and therefore contribute to infertility. Fertility treatment is challenging in women with higher body mass indices and monitoring of ovarian response with ultrasound can be limited as a result. Complications and adverse outcomes in those with higher body mass indices are however, not just limited to fertility treatments. The incidence of pregnancy complications such miscarriage and congenital anomalies are also increased in women in the obese category. The British Fertility Society have recommended that fertility treatment should be deferred until a BMI under 35 kg/m2 is achieved, and that in women where treatment is less time sensitive, a BMI of less than 30 kg/m2 is preferable10 .

Long term prognosis

Although data on long term outcomes in women with PCOS are conflicting, symptoms associated with PCOS such as obesity, dyslipidaemia and anovulation may result in long term complications including type II diabetes, cardiovascular disease and endometrial hyperplasia. The prevalence of gestational diabetes, impaired glucose tolerance and type II diabetes have been found to be significantly increased in women with PCOS11,12 . International guidelines suggest that glycaemic control should be assessed at diagnosis in this population and one to three yearly thereafter4 . Although an increased risk of cardiovascular disease in women with PCOS has not been quantified to date, women with PCOS often carry additional risk factors for cardiovascular disease such as increased BMI, increased waist Figure 1 : Typical sonographic appearance of a polycystic ovary with multiple peripheral follicles

circumference, dyslipidaemia and hypertension. It is recommended that these risk factors be screened for, assessed and monitored on an ongoing basis in this population. Although the relative incidence still remains low, women with PCOS have a two to six-fold increased risk of endometrial cancer13. It is crucial for women with amenorrhea to shed their endometrium at least every three months in order to reduce the risk of endometrial hyperplasia, a precancerous condition which can lead to endometrial cancer over time. This occurs as a result of chronic exposure to oestrogen that is unopposed by progesterone. Healthcare professionals need to be aware of this increased risk and have a low threshold for investigation of abnormal uterine bleeding in women with PCOS.

Conclusion

Polycystic Ovary Syndrome is a common condition in women of reproductive age. It is often undiagnosed due to its heterogenous phenotype. Early recognition is crucial to allow appropriate management of symptoms and sequelae, which can have major implications on a woman’s quality of life. A multidisciplinary, individualised approach to care can provide optimisation of women’s health and prevent short and long term complications including type II diabetes, cardiovascular disease, endometrial cancer and infertility in women with PCOS.

Further Reading:

• HSE PCOS Overview: https:// www2.hse.ie/conditions/polycysticovary-syndrome/ • EInternational evidence-based guideline for the assessment and management of polycystic ovary syndrome (PCOS) S : https://www. eshre.eu/Guidelines-and-Legal/

Guidelines/Polycystic-Ovary-

Syndrome • RCOG Patient Information Leaflet PCOS : https://www.rcog.org.uk/en/ patients/patient-leaflets/polycysticovary-syndrome-pcos-what-itmeans-for-your-long-term-health/

References:

1. Miazgowski T, Martopullo I, Widecka J, Miazgowski B, Brodowska A.

National and regional trends in the prevalence of polycystic ovary syndrome since 1990 within Europe: the modeled estimates from the Global Burden of Disease Study 2016. Archives of Medical Science: AMS. 2021;17(2):343. 2. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and metaanalysis. Human reproduction. 2016;31(12):2841-55. 3. Balen AH. Polycystic Ovary Syndrome (PCOS). TheObstetrician and Gynaecologist. 2017. 4. Teede HJ, Misso ML, Boyle JA, Garad RM, McAllister V, Downes L, et al. Translation and implementation of the Australian-led

PCOS guideline: clinical summary and translation resources from the International Evidence-based

Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Medical Journal of Australia. 2018;209:S3-S8. 5. Huber-Buchholz M-M, Carey D, Norman R. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. The Journal of Clinical Endocrinology & Metabolism. 1999;84(4):1470-4. 6. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ.

Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism. 2003;88(2):812-9. 7. Thomson RL, Buckley JD, Lim SS, Noakes M, Clifton PM, Norman RJ, et al. Lifestyle management improves quality of life and depression in overweight and obese women with polycystic ovary syndrome. Fertility and sterility. 2010;94(5):1812-6. 8. RCOG. Long-term consequences of polycystic ovary syndrome. 2014. 9. Dokras A, Stener-Victorin E, Yildiz BO, Li R, Ottey S, Shah D, et al. Androgen Excess-Polycystic

Ovary Syndrome Society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome. Fertility and sterility. 2018;109(5):888-99. 10. Balen AH, Anderson RA, Policy, BFS PCot. Impact of obesity on female reproductive health:

British fertility society, policy and practice guidelines. Human Fertility. 2007;10(4):195-206. 11. Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and risk factors of type 2 diabetes in a nationwide population of women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism. 2017;102(10):3848-57. 12. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction update. 2010;16(4):347-63. 13. Charalampakis V, Tahrani AA, Helmy A, Gupta JK, Singhal R.

Polycystic ovary syndrome and endometrial hyperplasia: an overview of the role of bariatric surgery in female fertility. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2016;207:220-6.

Perinatal Mental Health During Covid-19: A Delicate Balance

Written by Dr Laura McHugh, Psychologist in Clinical Training, NUI Galway

During pregnancy, women experience both physiological and psychological changes which can place them at risk of developing mental health difficulties1. Mental health difficulties during pregnancy are related to adverse outcomes for both mother and infant. For the infant, maternal anxiety and depression are associated with a shorter gestational period, low birth weight and adverse neurodevelopmental outcomes2 , as well as reduced postpartum bonding3. For mothers who experience mental health difficulties during pregnancy, impacted sleep, conflict with partners, feelings of worry, and loss of a sense of self are described by women4, as well as impacted parent-infant bonding3 . The addition of the Coronavirus (SARS-CoV2) (Covid-19) pandemic to the period of pregnancy may potentially increase the risk of mental health difficulties for women during this time5. Restrictions on the presence of partners during antenatal appointments and the period of labour have been put in place to varied extents across hospital groups6. Remote consultations with healthcare staff, social distancing and home isolation have also been introduced across Ireland. The rationale for all of these restrictions being to prevent the spread of infection of the Covid-19 virus, and minimize exposure for vulnerable groups such as expectant mothers7 . These preventative measures in response to the Covid-19 pandemic may have unintended consequences for the mental health of women during pregnancy5. The public health measure in response to Covid-19 mean that the typical ‘right of passage’ experiences for women during pregnancy, such as a therapeutic connection with healthcare providers, social interaction with other pregnant women, and celebrations amongst friends and family may not be accessible to women6 . The causes of stress and worry that have been identified by pregnant women during the

pandemic include fear of catching or spreading Covid-19, changes to the organisation of perinatal care, online consultations with healthcare staff, and not having a partner present during birth8 . Continued experiences of dailystressors for women has been related to adverse mental health outcomes during the period of pregancy9. During the pandemic, studies have been carried out across the globe to explore the mental health of pregnant women. These studies have been carried out in Italy10, the United States11 , China12 and across Europe, inclusive of Ireland13. These studies indicate a significant prevalence of anxiety and depression in pregnant women during the Covid-19 pandemic8. Studies which surveyed expectant mothers before the pandemic and during the pandemic found pregnant mothers during the pandemic were more likely to experience clinical levels of anxiety and depression than the mothers who were surveyed before the pandemic14 . Research observing this uptrend of mental health difficulties among expectant mothers during Covid-19 have highlighted the need to monitor the mental health status of pregnant women at this time13 . Social support is protective against mental health difficulties for pregnant women, particularly for first-time mothers15 . The availability of emotional and practical supports from friends and family during pregnancy is associated with lower levels of emotional distress for women16 . Women consider access to social ‘safety nets’, in the form of connections with others and partner support, as key to reducing feelings of isolation during pregnancy17. The availability of these ‘safety nets’ are a continued challenge for women during the pandemic. Continued spousal support during the period of labour is also of particular importance. Cochrane reviews summarising research in this area have indicted the importance of continued spousal support during labour18. Spousal support serves the function of helping to communicate preferences to a health worker, support in decision-making, and providing encouragement, reassurance, and physical comfort during labour18 . The presence of continuous one-to-one support for women during labour was related to shorter labours, lower rates of caesarean births, lower rates of intrapartum analgesia, positive feelings about the birth experience and lower rates of depressive symptomology post-birth18 . Conversely, low support during labour and birth is a risk factor for the development of postnatal post-traumatic stress disorder (PTSD)19 . To this end, the World Health Organization (WHO) guidance recommends the presence of a companion of the woman's choice during labour and childbirth, to improve labour outcomes and women's satisfaction with services20 . However, women may not only be vulnerable in terms of mental health during pregnancy, but may also be vulnerable medically. During pregnancy, the immune system is partially supressed, making women more vulnerable to viral infections21. The risks to both mother and infant medically due to Covid-19 are still being understood21. Synthesis of the possible implications of Covid-19 infection for pregnant women note the limited number of case reports to draw upon, with small and diverse samples making generalisations challenging22 . However, some data has suggested that if infected with Covid-19, pregnant women experience more severe illness, are more likely to experience pre-term births and increased neonatal mortality22,23. Research considering these findings, and comparing the pathogenic potential of Covid-19 to other members of the coronavirus family, such as Middle East respiratory syndrome (MERS-CoV), recommend that pregnant women are considered high-risk and the implementation of protective steps to monitor and prevent infection21 . The mental health needs of pregnant women have been overshadowed by other pressing issues in healthcare settings during the Covid-19 pandemic5 . Research during the pandemic has demonstrated an uptrend in perinatal mental health difficulties for women. Fear of the spread of Covid-19, changes to perinatal care, online consultations, and not having a partner present during birth are ongoing stressors for women during pregnancy. However, the availably of practical and emotional support from loved ones during pregnancy, and continuous one-to-one support during labour, are protective against mental health difficulties and related to positive outcomes during labour and post birth. The need for focus on the mental health of pregnant women during the pandemic, and to proactively develop strategies to monitor and protect against mental health difficulties for women has been a central recommendation of research5 .

References available on request