When should treatment be started in a reproductive‑age woman with polycystic ovary syndrome (PCOS) and what are the indications?

Indications for Treatment in PCOS

All reproductive-age women diagnosed with PCOS require treatment at the time of diagnosis, with the specific therapeutic approach determined by their primary clinical concerns: menstrual irregularity/endometrial protection, hyperandrogenic symptoms (hirsutism/acne), fertility goals, or metabolic complications. 1, 2

Treatment Algorithm Based on Primary Clinical Concern

For Menstrual Irregularity and Endometrial Protection

Combined oral contraceptives (COCs) are first-line treatment for women not attempting pregnancy, as they restore regular menses, suppress ovarian androgen secretion, increase sex hormone-binding globulin, and critically reduce endometrial cancer risk. 1, 2, 3

• COCs containing norgestimate (e.g., Sprintec) are preferred due to favorable side effect profiles 1
• Standard regimens include 21-24 hormone pills followed by 4-7 placebo pills 1
• Additional benefits include decreased menstrual cramping, reduced blood loss, and acne improvement 1

For women with contraindications to COCs or who decline them, medroxyprogesterone acetate 10 mg daily for 12-14 days per month is recommended to induce withdrawal bleeding and provide endometrial protection. 1, 4

• Alternative options include oral micronized progesterone 200 mg daily for 12-14 days per month (superior safety profile) or dydrogesterone 10 mg daily for 12-14 days 1
• Monthly cycling (every 28 days) is mandatory to maintain endometrial protection 1

For Hyperandrogenic Manifestations (Hirsutism/Acne)

COCs are first-line therapy for hirsutism and acne, with antiandrogens added only after 3-6 months of optimal-dose COC therapy if symptoms remain bothersome. 1, 2, 5

Spironolactone 50-100 mg daily should be added when clinically significant hirsutism, acne, or androgenic alopecia persists after 3-6 months of full-dose COC therapy (≥30-35 µg ethinyl estradiol with drospirenone, norgestimate, or levonorgestrel) plus lifestyle modifications. 2

• The combination of antiandrogen plus COC is more effective than either treatment alone 1
• Clinical improvement is typically observed by 6 months of combined therapy 2
• Critical pitfall: Never prescribe spironolactone without confirmed effective contraception due to teratogenic risk 2, 4

For Fertility/Ovulation Induction

Clomiphene citrate 50 mg daily for 5 days is first-line ovulation induction treatment for women with PCOS attempting pregnancy, with approximately 80% ovulating and 50% of those conceiving. 1, 4, 3

• Letrozole demonstrates superior live birth and pregnancy rates compared to clomiphene and is increasingly preferred 4
• Low-dose gonadotropin therapy is second-line for clomiphene non-responders 1, 2
• Do not exceed clomiphene dosage and duration recommendations, as this worsens endometrial receptivity 4

For Metabolic Complications

All women with PCOS require metabolic screening at diagnosis regardless of body weight, including fasting glucose followed by 2-hour glucose tolerance test, fasting lipid profile, BMI, and waist-hip ratio. 6, 2, 4, 3

• Women with PCOS should be screened for cardiovascular risk factors every 6-12 months, including weight changes, blood pressure, fasting lipid panel, and glycemic control 6
• Metformin 500-2000 mg daily should be added when insulin resistance or glucose intolerance is documented, lifestyle modifications alone are insufficient for metabolic control, or the patient has obesity or elevated cardiovascular risk factors 2, 3

Mandatory Lifestyle Intervention for All Patients

Lifestyle modification targeting 5-10% weight loss through a 500-750 kcal/day energy deficit is the foundational first-line treatment for ALL women with PCOS, improving metabolic, reproductive, and psychological outcomes. 6, 2, 4

• Target total intake of 1,200-1,500 kcal/day, adjusted for individual requirements 2
• Perform at least 250 minutes/week of moderate-intensity activity for weight loss, plus muscle strengthening on 2 non-consecutive days/week 2
• Even 5% weight reduction substantially improves ovulation, fertility, insulin sensitivity, and reduces endometrial cancer and cardiovascular disease risks 6
• Weight loss is beneficial even in normal-weight PCOS patients for metabolic and reproductive outcomes 6

Special Populations Requiring Immediate Treatment

Women with marked virilization or rapid onset of symptoms require immediate evaluation for potential androgen-secreting tumor before initiating standard PCOS treatment. 3

Adolescent patients should have evaluation delayed until 2 years after menarche, and all three Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, polycystic ovaries) must be met before diagnosis. 3

Critical Metabolic Risks Requiring Aggressive Management

Women with PCOS have twice the prevalence of metabolic syndrome compared to the general population and are four times more likely to develop type 2 diabetes mellitus. 3

• PCOS is associated with increased risk of cardiovascular disease, with endothelial dysfunction and subclinical atherosclerosis commonly present 6
• East Asian women with PCOS have the highest prevalence of metabolic syndrome despite lower BMI 6
• Psychological factors including anxiety, depression, and eating disorders are prevalent and must be addressed, as untreated emotional or binge eating hinders weight management 6, 2

Common Pitfalls to Avoid

• Do not delay lifestyle intervention—it must be the foundation of treatment, not an afterthought 2, 4
• Do not neglect metabolic screening even in normal-weight PCOS patients, as metabolic complications occur across all BMI categories 2, 4
• Do not use spironolactone in patients attempting to conceive due to contraindication in pregnancy 4
• Do not add spironolactone before 3 months of COC therapy unless hyperandrogenic symptoms severely impair quality of life 2