What are the recommended hormone replacement therapy (HRT) options for perimenopausal women?

From the Guidelines

Hormone replacement therapy (HRT) for perimenopausal women should be individualized, considering the lowest effective dose and the woman's medical history, risk factors, and personal preferences, with the goal of managing symptoms while minimizing risks 1. When considering HRT options, it's essential to weigh the benefits against the potential harms. For women with an intact uterus, combined estrogen-progestogen therapy is typically recommended to prevent endometrial hyperplasia. The choice of estrogen and progestogen, as well as the dosage, should be based on the individual woman's needs and medical history. Some key points to consider when prescribing HRT include:

• Starting with the lowest effective dose to minimize risks
• Using transdermal options, such as estradiol patches, which may have a lower risk of thrombosis compared to oral estrogens
• Considering low-dose vaginal estrogen products for local symptoms without significant systemic absorption
• Regularly reassessing the need for continued HRT, typically every 3-5 years
• Discussing the potential risks of HRT, including breast cancer, stroke, and venous thromboembolism, particularly with longer-term use, as noted in the Women's Health Initiative (WHI) study 1. It's crucial to develop a shared decision-making approach with the patient, taking into account her individual risk factors, preferences, and symptoms to determine the best course of treatment.

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. For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding. For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms.

The recommended Hormone Replacement Therapy (HRT) options for perimenopausal women include:

• Estradiol (PO): 1 to 2 mg daily, adjusted as necessary to control symptoms 2
• Conjugated estrogens (PO): dosage not specified, but should be used with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman 3 Key considerations:
• 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
• Women with a uterus should also be initiated on progestin to reduce the risk of endometrial cancer
• Patients should be reevaluated periodically to determine if treatment is still necessary

From the Research

Perimenopausal Hormone Replacement Therapy (HRT) Options

The following are recommended HRT options for perimenopausal women:

• Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75% 4
• Oral and transdermal estrogen have similar efficacy 4
• Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) are commonly used hormonal treatments 4
• Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer 4
• Bioidentical estrogens approved by the US Food and Drug Administration are also available to treat vasomotor symptoms 4

Progestogen Therapy

Progestogen is added to estrogen therapy to prevent endometrial hyperplasia and cancer in women with an intact uterus:

• The primary role of progestogen in postmenopausal hormone therapy is endometrial protection 5
• Unopposed estrogen therapy is associated with a significantly increased risk of endometrial hyperplasia and adenocarcinoma 5
• Adding the appropriate dose and duration of progestogen to estrogen therapy lowers the risk of endometrial hyperplasia and adenocarcinoma 5
• Natural progesterone and dydrogesterone are associated with a lower risk of breast cancer compared to other progestins 6

Non-Hormonal Options

Non-hormonal approaches are available for women who are not candidates for hormonal treatments:

• Citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65% 4
• Low-dose vaginal estrogen is associated with subjective improvement in genitourinary syndrome of menopause (GSM) symptom severity by approximately 60% to 80% 4