Should progesterone be increased with estradiol in postmenopausal vasomotor symptoms?

From the Guidelines

When increasing estradiol for postmenopausal vasomotor symptoms, you should also increase progesterone if the patient has an intact uterus to prevent endometrial hyperplasia and cancer. For women with a uterus, progesterone is essential to prevent endometrial hyperplasia and cancer that can result from unopposed estrogen, as noted in the guidelines for hormone therapy 1. Typically, for every 0.5 mg increase in estradiol, increase micronized progesterone by 100 mg daily. A standard regimen might include estradiol 0.5-1 mg daily with micronized progesterone 100-200 mg daily for 12-14 days per month in a cyclic regimen, or continuously if using lower progesterone doses. Some key points to consider when prescribing hormone therapy for postmenopausal vasomotor symptoms include:

• Women who have had a hysterectomy do not require progesterone with their estrogen therapy, as stated in the guidelines 1.
• The progesterone component often causes side effects like breast tenderness, mood changes, and bloating, so using the minimum effective dose is recommended.
• The protective effect of progesterone on the endometrium occurs through downregulation of estrogen receptors and promotion of enzymatic conversion of estradiol to less active metabolites in endometrial tissue.
• Estrogen transdermal formulations may be preferred over other formulations due to lower rates of venous thromboembolism (VTE) and stroke, as suggested by the guidelines 1.
• Micronized progestin may be preferred over medroxyprogesterone acetate (MPA) due to lower rates of VTE and breast cancer risk. It's also important to consider alternative treatments for vasomotor symptoms, such as paroxetine, venlafaxine, gabapentin, or clonidine, for women who are unable or unwilling to use hormonal therapy, as recommended in the guidelines 1.

From the FDA Drug Label

The pharmacokinetics of progesterone capsules have not been assessed in low body weight or obese patients. Progestins with estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

The FDA drug label does not answer the question.

From the Research

Treatment of Postmenopausal Vasomotor Symptoms

• The most effective treatment for vasomotor symptoms is menopausal hormone therapy, which typically includes a combination of estrogen and progesterone 2, 3, 4.
• When increasing estradiol, it is common to also increase progesterone to balance the hormonal regimen and minimize the risk of endometrial hyperplasia in women with a uterus 3, 5.
• Studies have shown that transdermal estradiol and progesterone (O+P) have the highest probability of being the most effective treatment for vasomotor symptom relief 3.
• Progesterone monotherapy has also been shown to be effective in reducing vasomotor symptoms, with a dose-dependent improvement in symptoms 6.
• The decision to increase progesterone when increasing estradiol should be individualized and based on the specific needs and medical history of the patient, as well as the guidance of a healthcare professional 2, 5.

Key Considerations

• The benefits and risks of hormone therapy should be carefully weighed, taking into account the individual patient's health status, age, and medical history 2, 5.
• Alternative treatments, such as non-hormonal pharmacologic therapies, may be considered for women who cannot or choose not to use hormone therapy 2, 4.
• The effectiveness of different treatments may vary depending on the specific population being studied, such as women with natural menopause versus those with surgical menopause 3, 5.