What are the considerations for Hormone Replacement Therapy (HRT) in women with Polycystic Ovary Syndrome (PCOS)?

Hormone Replacement Therapy Considerations in Women with PCOS

For women with PCOS requiring hormone replacement therapy (HRT), transdermal 17β-estradiol with micronized progesterone is the preferred regimen due to its favorable cardiovascular and metabolic profile, which is particularly important given the increased cardiometabolic risks already present in PCOS. 1, 2

Estrogen Component Selection

• Transdermal 17β-estradiol is the preferred estrogen formulation as it mimics physiological serum estradiol concentrations, avoids hepatic first-pass effect, and provides more beneficial effects on lipid profiles, inflammation markers, and blood pressure 1
• The recommended dosage is 50-100 μg of transdermal 17β-estradiol daily 1
• 17β-estradiol is strongly preferred over ethinylestradiol or conjugated equine estrogens for women with PCOS due to their already elevated risk of metabolic complications 1, 2
• Transdermal delivery is particularly important for women with PCOS who have hypertension or insulin resistance 3, 2

Progestogen Component

• Micronized natural progesterone (100-200 mg/day for 12-14 days per month) is the first-choice progestogen for women with PCOS due to its more favorable cardiovascular risk profile 1, 2
• Progestogen must be given in combination with estrogen therapy to protect the endometrium in women with an intact uterus 3, 4
• Dydrogesterone (10 mg/day for 12-14 days) is a reasonable alternative if micronized progesterone is not tolerated 3, 2
• Avoid progestins with anti-androgenic effects in women with PCOS as they may worsen the hypoandrogenism that can occur with HRT 3

Special Considerations for PCOS

• Women with PCOS have increased baseline risk of venous thromboembolism (1.5-times higher) which can be further elevated with hormonal therapy, making the transdermal route particularly important 5
• PCOS patients have higher prevalence of insulin resistance and glucose intolerance, so HRT regimens should minimize impact on glucose metabolism 5, 6
• Women with PCOS have altered lipid profiles (lower HDL size, higher LDL particle number) that should be considered when selecting HRT 5
• Cardiovascular risk assessment (blood pressure, weight, smoking status) should be performed annually in women with PCOS on HRT 3, 2

Administration Regimens

• A sequential regimen (continuous estrogen with cyclic progestogen for 12-14 days every 28 days) is generally recommended for women with PCOS 1, 2
• Continuous combined regimens can be considered when the woman prefers to avoid withdrawal bleeding 2
• Patient preference for route and method of administration should be considered when prescribing, as should contraceptive needs 3

Duration of Therapy and Monitoring

• HRT should be continued at least until the average age of natural menopause (50-51 years) 3, 1
• Annual clinical review focusing on compliance and cardiovascular risk factors is recommended 3, 1
• Blood pressure, weight, and smoking status should be monitored annually, with other risk factors assessed if indicated 3
• No routine monitoring tests are required but may be prompted by specific symptoms or concerns 3

Common Pitfalls to Avoid

• Using ethinylestradiol-containing contraceptives instead of 17β-estradiol for HRT is not recommended for women with PCOS due to higher thrombotic risk and less favorable metabolic profiles 1, 7
• Failing to add progestogen in women with an intact uterus increases risk of endometrial hyperplasia and cancer, which is already elevated in PCOS due to chronic anovulation 3, 4
• Using inadequate doses that don't achieve physiological estrogen levels may not provide adequate protection against long-term health consequences 1
• Discontinuing HRT prematurely can increase risks of osteoporosis, cardiovascular disease, and urogenital atrophy 1

Contraindications and Cautions

• HRT is generally contraindicated in breast cancer survivors 3, 2
• For women with PCOS and hypertension, transdermal estradiol is strongly preferred 3, 2
• For women with PCOS and a history of migraine, HRT is not contraindicated, but dose/route adjustments may be needed if migraines worsen 3
• Women with PCOS should be informed that HRT has not been found to increase the risk of breast cancer before the age of natural menopause 3