Polycystic ovary syndrome (PCOS) is one of the most common metabolic disorders in premenopausal women. Between 2% and 26% of women of reproductive age are affected. As established in The Rotterdam consensus criteria, PCOS has a broad definition with two out of three of: a) polycystic ovaries (either 12 or more follicles or increased ovarian volume), b) oligo-ovulation or anovulation or c) clinical and/or biochemical signs of hyperandrogenism. Thyroid dysfunction, acromegaly and hyperprolactinaemia should be actively excluded.
The aetiology of this syndrome remains largely unknown, but evidence suggests that PCOS is a complex disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. Despite ongoing research, there is no definitive cure.
Symptoms and Signs
PCOS is therefore associated with the wide-ranging combination of abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. Signs of PCOS can arise during early puberty. PCOS presents with irregular menses, oligo- or amenorrhoea, anovulatory infertility, hirsutism, persistent acne, alopecia and obesity. Associated symptoms include hair loss, difficulty losing weight, severe acne and depression.
Confirmatory biochemical testing demonstrates an increase in testosterone and/or androstenedione, an increase in luteinising hormone (LH) with normal follicle-stimulating hormone (FSH), and a decrease in sex hormone binding globulin (SHBG) causing a raised ‘free androgen index’. Mid-follicular oestradiol may be normal but with low day 21 progesterone. Impaired glucose tolerance increases the risk of late-onset diabetes mellitus. Other late-onset complications include hypertension, cardiovascular disease and endometrial carcinoma.
Those at risk for PCOS and those with a confirmed PCOS diagnosis should be offered education, healthy lifestyle intervention, and therapeutic interventions targeting their individual symptoms. Timely implementation of individualized therapeutic interventions will improve overall management of PCOS during adolescence, prevent comorbidities and improve quality of life.
The mainstay of treatment is weight loss and prevention of obesity. Obesity exacerbates both symptomatology and the endocrine profile; obese women (BMI >30 kg/m2) should therefore be encouraged to lose weight. Importantly, weight loss improves the likelihood of ovulation and a healthy pregnancy. Specialist dietary advice provides a sustainable and compatible diet that reduces glycaemic load by lowering sugar content in favour of complex carbohydrates. An increase in physical activity is also important (minimum of 30 minutes per day of brisk exercise five times per week). Specialist referral maybe indicated if sleep apnoea/snoring leads to poor sleep and daytime lethargy.
Metformin is indicated in women with PCOS and impaired glucose tolerance or confirmed diabetes. Metformin can also improve insulin resistance and may cause modest weight loss. Orlistat (Anti-obesity drug) has been shown to be effective in small studies. The combination of metformin and an anti-obesity agent remains unproven. Bariatric surgery is effective in reducing the symptoms and metabolic abnormalities of morbidly obese women with PCOS. It should be considered as an option, particularly for those who have a BMI of greater than 40kg/m2.
Menstrual irregularity can be controlled with a low-dose combined oral contraceptive (COC) preparation. This will result in an artificial cycle and regular shedding of the endometrium. An alternative is a progestogen (such as medroxyprogesterone acetate or dydrogesterone) for 10–14 days every one to three months to induce a withdrawal bleed. Metformin is a second line if contraception is not required, as it can also regulate menses.
In women with anovulatory cycles, the lack of cyclical progesterone secretion results in unopposed oestrogen causing endometrial thickening and hence episodes of irregular uterine bleeding. Long term, this can lead to endometrial hyperplasia and even endometrial cancer. A withdrawal bleed should be induced if ultrasound assessment demonstrates endometrial thickness greater than 15 mm. Failure to induce a bleed should prompt endometrial sampling to exclude endometrial hyperplasia. The only young women to get endometrial carcinoma (<35years), which otherwise has a mean age of occurrence of 61 years in the UK, are those with anovulation secondary to PCOS or oestrogen-secreting tumours.
Anovulatory Infertility is a significant problem: Ovulation can be induced with anti-oestrogens such as Letrozole (aromatase inhibitor), Clomid (Clomiphene citrate) which is successful in inducing ovulation in 75–80% of women but associated with a 10% risk of multiple pregnancies. Metformin improves ovulation, but results in a live birth rate of only 7%.
Hyperandrogenism presents with a typical pattern of facial hirsutism that is best managed using a combination of electrolysis/laser treatment and hormonal therapy. The combination of 35 µg ethinyloestradiol with 2 mg cyproterone acetate (co-cyprindiol/dianette) has been widely and successfully used, although primarily licensed for treatment of acne. Antiandrogens such as Cyproterone acetate (CPA) and spironolactone can be given in addition to a COC, but are contraindicated during pregnancy and lactation due to feminisation of the male foetus. Barrier contraception should be advised in women who are sexually active.
Eflornithine (Vaniqa) is a topical skin preparation, which reduces the rate of growth of facial hair and has proved effective both alone and in combination with laser hair removal. Isotretinoin capsules (Roaccutane) decreases the size of the sebaceous glands in the skin in severe persistent acne.
Psychological issues should be considered in all women with PCOS. Depression and/or anxiety should be routinely screened for and, if present, assessed. If a woman with PCOS is positive on screening, further assessment and appropriate counselling and intervention should be offered by a qualified professional
Long-term Consequences of Polycystic Ovary Syndrome
Green-top Guideline No. 33 November 2014
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Information for you: Polycystic ovary syndrome: what it means for your long-term health
Metformin Therapy for the Management of Infertility in Women with Polycystic Ovary Syndrome. Morley LC, Tang TMH, Balen AH. RCOG. Scientific Impact Paper No. 13. BJOG 2017 ; 124:e306–e313.