What is the role of progesterone in postmenopausal (post-menstrual) women?

From the Guidelines

Progesterone therapy is generally not recommended for routine use in postmenopausal women unless it's part of a combined hormone therapy regimen with estrogen for those with an intact uterus. For postmenopausal women taking estrogen therapy who have not had a hysterectomy, progesterone (such as micronized progesterone 100-200 mg daily or medroxyprogesterone acetate 2.5-5 mg daily) should be added to prevent endometrial hyperplasia and cancer, as supported by the U.S. Preventive Services Task Force recommendation statement 1. Progesterone alone has limited benefits for typical menopausal symptoms like hot flashes and is not effective for preventing osteoporosis or cardiovascular disease in postmenopausal women. Some women may use progesterone (typically micronized progesterone 100-200 mg at bedtime) for sleep disturbances or mood symptoms, though evidence for this use is limited 1. Progesterone therapy carries potential risks including breast tenderness, bloating, mood changes, and possibly an increased risk of breast cancer when used long-term with estrogen 1. Any hormone therapy in postmenopausal women should be used at the lowest effective dose for the shortest duration necessary to manage symptoms, with regular medical follow-up to reassess the risk-benefit ratio, as emphasized by the FDA-approved indications for hormone therapy in postmenopausal women 1.

Key points to consider:

• The use of progesterone in postmenopausal women should be individualized, taking into account the woman's clinical situation, preferences, and values to maximize benefits over harms.
• The timing of initiation of hormone therapy relative to menopause onset may affect the balance of benefits and harms, although the evidence is not conclusive 1.
• Other effective interventions for preventing chronic diseases in postmenopausal women, such as weight-bearing exercise, bisphosphonates, and calcitonin, should be considered as alternatives to hormone therapy 1.

Overall, the decision to use progesterone therapy in postmenopausal women should be based on a careful evaluation of the potential benefits and harms, with consideration of the individual woman's needs and preferences, as recommended by the U.S. Preventive Services Task Force 1.

From the FDA Drug Label

Progesterone capsules are used in combination with estrogen-containing medications in a postmenopausal woman with a uterus (womb). Taking estrogen-alone increases the chance of developing a condition called endometrial hyperplasia that may lead to cancer of the lining of the uterus (womb) The addition of a progestin is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb). Prevention of Endometrial Hyperplasia: A postmenopausal woman with a uterus who is taking estrogens should take a single daily dose of 200 mg progesterone capsules at bedtime for 12 continuous days per 28-day cycle.

Progesterone Post-Menopausal Use:

• Progesterone capsules are used in combination with estrogen-containing medications in postmenopausal women with a uterus to reduce the risk of endometrial hyperplasia and cancer.
• The recommended dose for prevention of endometrial hyperplasia is 200 mg daily at bedtime for 12 continuous days per 28-day cycle 2.
• Progesterone capsules may increase the risk of certain adverse effects, including blood clots, stroke, and breast cancer, when used with estrogens 2, 2.

From the Research

Progesterone Post Menopausal

• Progesterone is commonly prescribed in combination with estrogen therapy for menopausal symptoms 3
• The efficacy of progestin-only treatment for menopausal symptoms has been investigated in several studies, with some reporting improvement in vasomotor symptoms (VMS) 3, 4
• A systematic review of seven randomized controlled trials (RCTs) found that progestin therapy led to an improvement of VMS in postmenopausal women, with the largest study administering oral progestin reporting a 58.9% improvement in VMS 3
• However, no study reported an improvement of mood symptoms, and side effects such as headaches and vaginal bleeding were significant in five of seven RCTs 3
• Transdermal progesterone has been shown to improve menopausal symptoms without adversely altering prothrombotic potential 4
• The optimal route and dosage of progestin monotherapy for menopausal symptoms has not been established, with administration ranging from 5 to 60 mg of transdermal progesterone and 10 to 20 mg oral medroxyprogesterone acetate 3

Hormone Replacement Therapy

• Hormone replacement therapy (HRT) is a common treatment for menopausal symptoms, with estrogen-based therapy being effective for vasomotor symptoms 5, 6
• However, HRT is not suitable for all women, and the decision to use HRT involves balancing the potential benefits against the potential risks 5, 6
• Current recommendations for HRT use in menopausal women emphasize the importance of individualized treatment and careful consideration of the potential risks and benefits 6

Alternative Therapies

• Nonhormonal treatment and alternative therapies, such as selective serotonin reuptake inhibitors and phytoestrogens, may be used to treat vasomotor symptoms in women who are contraindicated to hormone therapy or prefer fewer side effects 7