Polycystic Ovary Syndrome

Polycystic ovary syndrome is a heterogeneous endocrine disorder characterized by the combination of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, with underlying insulin resistance playing a central pathophysiological role in the majority of affected women, driving both the reproductive and metabolic manifestations of the condition.

Itis one of the most common endocrine disorders in women of reproductive age.

• Menstrual irregularity: oligomenorrhoea or amenorrhoea from chronic anovulation, typically presenting around the time of menarche or shortly after
• Hyperandrogenism: hirsutism (assessed clinically using the modified Ferriman-Gallwey score), acne, and, less commonly, androgenic alopecia
• Subfertility, from chronic anovulation
• Metabolic features: obesity or a tendency toward central adiposity (though a meaningful proportion of women with PCOS are of normal weight, "lean PCOS"), insulin resistance, and an increased long-term risk of type 2 diabetes, dyslipidemia, and metabolic syndrome
• Acanthosis nigricans (velvety, hyperpigmented skin, typically in the axillae and neck folds) as a clinical marker of significant insulin resistance

• Rotterdam criteria (2 of 3 required, with other causes excluded): oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound (defined as 20 or more follicles in either ovary, and/or ovarian volume of 10 mL or more, per updated 2018 international guideline thresholds using modern high-resolution transvaginal ultrasound)
• Exclude alternative causes before confirming diagnosis: TSH (thyroid dysfunction), prolactin (hyperprolactinemia), and 17-hydroxyprogesterone (late-onset congenital adrenal hyperplasia), which can all mimic the presentation
• Biochemical hyperandrogenism: total and free testosterone, with sex hormone binding globulin (SHBG) to calculate the free androgen index; markedly elevated testosterone should prompt exclusion of an androgen-secreting tumor
• LH:FSH ratio (classically elevated, though no longer part of formal diagnostic criteria given inconsistent utility) may be noted incidentally
• Metabolic screening: fasting glucose and/or HbA1c (or a 75g OGTT, particularly in higher risk women, including those with obesity, family history of diabetes, or planning pregnancy), and a lipid profile, given the elevated long-term metabolic risk

Management is tailored to the woman's primary concern (menstrual regulation, hirsutism/acne, fertility, or metabolic risk), since no single treatment addresses all aspects of the condition simultaneously.

Menstrual irregularity and endometrial protection (chronic anovulation causes unopposed estrogen exposure, raising endometrial hyperplasia risk if untreated):

• Combined oral contraceptive is first line, regulating cycles and reducing hyperandrogenic symptoms; formulations containing an antiandrogenic progestogen (e.g. cyproterone acetate or drospirenone containing pills) may offer additional benefit for hirsutism/acne, though evidence of superiority over other COCP formulations for this specific indication is modest
• Cyclical progestogen or the levonorgestrel-releasing IUD for endometrial protection where estrogen-containing contraception is declined or contraindicated

Hirsutism and acne:

• COCP as above is first line; if inadequate after 6 months, antiandrogen therapy (e.g. spironolactone 50 to 200 mg PO od, off-label use, with reliable contraception mandated given feminization risk to a male fetus) may be added, alongside cosmetic measures (laser hair removal, topical eflornithine for facial hirsutism)

Weight management and metabolic risk:

• Lifestyle modification (diet and exercise, even modest weight loss of 5 to 10% can restore ovulation and improve metabolic parameters) is foundational
• Metformin 500 mg PO od, titrated up to 500 mg to 1 g bd-tds (maximum typically 2 to 2.5 g/day), improves insulin sensitivity and can help restore ovulatory cycles, particularly useful in women with significant insulin resistance or where combined with lifestyle measures for weight management; also used as an adjunct to fertility treatment
• Regular metabolic screening (glucose/HbA1c, lipids) given long-term cardiovascular and diabetes risk

Fertility:

• Weight loss is first line where BMI is elevated, given its independent positive effect on ovulation
• Letrozole 2.5 to 5 mg PO od on cycle days 2 to 6 (or 3 to 7) is now first line pharmacological ovulation induction, having demonstrated superior live birth rates compared with clomiphene in trials
• Clomiphene citrate 50 mg PO od for 5 days (starting cycle day 2 to 5), titrated up to 100 to 150 mg/day if no response, remains a widely used alternative
• Metformin as an adjunct to ovulation induction, particularly in women with significant insulin resistance
• Gonadotropin therapy or laparoscopic ovarian drilling for clomiphene/letrozole-resistant anovulation, under fertility specialist care
• IVF where first and second line ovulation induction measures fail, or additional fertility factors are present

Referral: gynecology or reproductive endocrinology for diagnostic confirmation and management planning; fertility services where pregnancy is desired and first-line ovulation induction is unsuccessful; dermatology for refractory hirsutism/acne; endocrinology for significant metabolic derangement requiring more intensive management.