What is the recommended regimen for a patient requiring estrogen and progesterone therapy?

From the Guidelines

The recommended regimen for a patient requiring estrogen and progesterone therapy is to use combined 17βE and progestin patches as a first choice, with 17βE administered either transdermally via patches releasing 50 to 100 μg 24 hourly, or via vaginal gel, with doses ranging from 0.5 to 1 mg daily, and progestin such as levonorgestrel, with the goal of improving compliance to treatment and minimizing risks 1.

Key Considerations

• The choice of regimen should be based on the patient's individual needs and preferences, with consideration of factors such as the presence of an intact uterus, cardiovascular risk factors, and the desire for contraception or menstrual cycle regulation.
• Transdermal 17βE can be administered continuously, with oral or vaginal progestin added cyclically for 12-14 days every 28 days, with adult doses of oral progestin depending on the doses of estrogen administered 1.
• Among progestins, micronized progesterone (MP) is the first choice due to its association with a lower risk of cardiovascular disease and venous thromboembolism, as well as its endometrial protective effects 1.
• The dose of 17βE should be adjusted according to each woman's tolerance and feeling of wellbeing, with the goal of minimizing side effects and maximizing symptom relief.
• Hormone replacement therapy (HRT) in cancer survivors with premature ovarian insufficiency (POI) should be continued until the average age of spontaneous menopause (45-55 years), with the decision to stop or continue HRT thereafter based on individual risks, family history, personal feelings, and relevance of menopausal symptoms 1.

Important Safety Considerations

• Patients with a history of breast cancer or those at high risk for breast cancer should be closely monitored, with annual imaging and promotion of breast self-examination starting at age 25 years 1.
• Breast MRI may be considered for high-risk young women, as it has been shown to increase the early detection of cancer in this population 1.
• Progestins with anti-androgenic effects, such as norethisterone, should be avoided in patients with iatrogenic POI, as they may worsen hypoandrogenism and diminish libido or impair sexual function 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

The recommended regimen for a patient requiring estrogen and progesterone therapy is to use the lowest effective dose of estrogen and progesterone for the shortest duration consistent with treatment goals and risks.

• For women with a uterus, a progestin should be initiated to reduce the risk of endometrial cancer.
• The lowest dose and regimen that will control symptoms should be chosen.
• Medication should be discontinued as promptly as possible.
• Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals 2.
• Administration should be cyclic (e.g., 3 weeks on and 1 week off) 2.

From the Research

Estrogen and Progesterone Therapy

The recommended regimen for a patient requiring estrogen and progesterone therapy involves several considerations, including the type of progestogen used, the dosage, and the route of administration.

• The use of micronized progesterone is recommended as part of combined hormone replacement therapy (HRT) in women with an intact uterus, as it has been shown to have a protective effect on the endometrium against the proliferative effects of estrogens 3.
• Continuous combined estrogen and progestogen therapy is preferred over cyclical regimens, as it provides better protection against endometrial hyperplasia and cancer 3, 4.
• The route of estrogen administration is also important, with transdermal estradiol being associated with a lower risk of venous thromboembolism and other cardiovascular events compared to oral HRT 4.
• The dosage of estrogen and progestogen should be individualized to minimize risks and side effects, with lower doses often used in combination with cyclic progestins every 3 to 4 months 5.

Progestogen Options

Different progestogens have varying effects on the breast and breast cancer risk.

• Micronized progesterone has been shown to have a more favorable effect on risk biomarkers for postmenopausal breast cancer compared to medroxyprogesterone acetate (MPA) 6.
• MPA has been associated with an increased risk of invasive breast cancer, believed to be due to its promoter effect 3.
• Natural, "body-identical" progesterone, such as micronized progesterone, may be the optimal progestogen in terms of cardiovascular effects, blood pressure, and breast cancer risk 4.

Treatment Considerations

When considering estrogen and progesterone therapy, several factors should be taken into account.

• The patient's individual risk/benefit ratio should be assessed, including their risk of osteoporotic fractures, cardiovascular disease, and breast cancer 4, 5.
• The patient's symptoms and medical history should be considered, with treatment tailored to their specific needs 7.
• The potential side effects of estrogen and progestogen therapy, such as vaginal bleeding and breast tenderness, should be discussed with the patient and monitored during treatment 5, 7.