Polycystic ovary syndrome (PCOS) is the triad of oligo-ovulation resulting in oligomenorrhea, hyperandrogenism and, often, an excess number of small antral follicles on high-resolution pelvic ultrasound. One meta-analysis reported that, in women of reproductive age, the prevalence of PCOS was 10% using the Rotterdam-European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) criteria1 and 6% using the National Institutes of Health 1990 diagnostic criteria.2 (See “The PCOS trinity—3 findings in one syndrome: oligo-ovulation, hyperandrogenism, and a multifollicular ovary.”3)
PCOS is caused by abnormalities in 3 systems: reproductive, metabolic, and dermatologic. Reproductive abnormalities commonly observed in women with PCOS include4:
- an increase in pituitary secretion of luteinizing hormone (LH), resulting from both an increase in LH pulse amplitude and LH pulse frequency, suggesting a primary hypothalamic disorder
- an increase in ovarian secretion of androstenedione and testosterone due to stimulation by LH and possibly insulin
- oligo-ovulation with chronically low levels of progesterone that can result in endometrial hyperplasia
- ovulatory infertility.
Metabolic abnormalities commonly observed in women with PCOS include5,6:
- insulin resistance and hyperinsulinemia
- excess adipose tissue in the liver
- excess visceral fat
- elevated adipokines
- obesity
- an increased prevalence of glucose intolerance and frank diabetes.
Dermatologic abnormalities commonly observed in women with PCOS include7:
- facial hirsutism
- acne
- androgenetic alopecia.
Given that PCOS is caused by abnormalities in the reproductive, metabolic, and dermatologic systems, it is appropriate to consider multimodal hormonal therapy that addresses all 3 problems. In my practice, I believe that the best approach to the long-term hormonal treatment of PCOS for many women is to prescribe a combination of 3 medicines: a combination estrogen-progestin oral contraceptive (COC), an insulin sensitizer, and an antiandrogen.
The COC reduces pituitary secretion of LH, decreases ovarian androgen production, and prevents the development of endometrial hyperplasia. When taken cyclically, the COC treatment also restores regular withdrawal uterine bleeding.
An insulin sensitizer, such as metformin or pioglitazone, helps to reduce insulin resistance, glucose intolerance, and hepatic adipose content, rebalancing central metabolism. It is important to include diet and exercise in the long-term treatment of PCOS, and I always encourage these lifestyle changes. However, my patients usually report that they have tried multiple times to restrict dietary caloric intake and increase exercise and have been unable to rebalance their metabolism with these interventions alone. Of note, in the women with PCOS and a body mass index >35 kg/m2, bariatric surgery, such as a sleeve gastrectomy, often results in marked improvement of their PCOS.8
The antiandrogen spironolactone provides effective treatment for the dermatologic problems of facial hirsutism and acne. Some COCs containing the progestins drospirenone, norgestimate, and norethindrone acetate are approved by the US Food and Drug Administration for the treatment of acne. A common approach I use in practice is to prescribe a COC, plus spironolactone 100 mg daily plus metformin extended-release 750 mg to 1,500 mg daily.
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