What is the role of Medroxyprogesterone (Progestin) in Hormone Replacement Therapy (HRT) for menopause?

From the Guidelines

Medroxyprogesterone acetate should not be used as a first-line treatment for menopausal hormone therapy due to the potential risks and lack of convincing evidence on its benefits. The US Preventive Services Task Force (USPSTF) has evaluated the benefits and harms of clinical interventions intended to prevent disease, and their recommendation statement notes that the estimates of the absolute risks and benefits are derived primarily from the Women's Health Initiative (WHI) study, which used oral conjugated equine estrogen with or without oral medroxyprogesterone acetate 1.

The USPSTF has clarified that there is no convincing evidence to assert that the ultimate balance of benefits and harms might be substantially altered by using different approaches, including different forms, dosages, and routes of administration of estrogen and progestin therapies 1. Additionally, the American Heart Association and the American Congress of Obstetricians and Gynecologists recommend against the use of menopausal hormone therapy for the primary or secondary prevention of cardiovascular disease 1.

Some key points to consider when evaluating the use of medroxyprogesterone acetate as HRT in menopause include:

• The potential risks and benefits of hormone therapy, including the increased risk of cardiovascular disease, breast cancer, and endometrial cancer
• The lack of convincing evidence on the benefits of medroxyprogesterone acetate as a first-line treatment for menopausal hormone therapy
• The importance of using the lowest effective dose for the shortest duration needed to manage symptoms, with regular medical follow-up to reassess benefits and risks
• The availability of alternative progestogens, such as micronized progesterone, which may be better tolerated by some women.

Overall, the decision to use medroxyprogesterone acetate as HRT in menopause should be made on a case-by-case basis, taking into account the individual woman's medical history, symptoms, and preferences, as well as the potential risks and benefits of treatment 1.

From the FDA Drug Label

Reduction of Endometrial Hyperplasia in Postmenopausal Women Receiving Daily 0. 625 mg Conjugated Estrogens When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive days per month, in postmenopausal women receiving daily 0. 625 mg conjugated estrogens, either beginning on the 1st day of the cycle or the 16th day of the cycle.

Medroxyprogesterone acetate can be used as part of Hormone Replacement Therapy (HRT) in menopausal women with a uterus to reduce the risk of endometrial hyperplasia and endometrial cancer when used in combination with estrogen. The recommended dosage is 5 or 10 mg daily for 12 to 14 consecutive days per month, in combination with daily 0.625 mg conjugated estrogens 2.

Key points:

• Medroxyprogesterone acetate is used to reduce the risk of endometrial cancer in postmenopausal women with a uterus who are taking estrogen.
• The recommended dosage is 5 or 10 mg daily for 12 to 14 consecutive days per month.
• Medroxyprogesterone acetate should be used in combination with estrogen to reduce the risk of endometrial hyperplasia and endometrial cancer.

From the Research

Medroxyprogestterone Use as HRT in Menopause

• Medroxyprogestterone acetate (MPA) is a progestogen used in combined menopausal hormone therapy (MHT) for endometrial protection in women with an intact uterus 3.
• The use of MPA in MHT has been studied in several clinical trials, with varying results regarding its efficacy and safety 4, 5.
• A study published in 2001 found that low-dosage esterified estrogens opposed by MPA at 6-month intervals was effective in reducing endometrial hyperplasia and vaginal bleeding in postmenopausal women 5.
• Another study published in 2017 discussed the evolving role of oral hormone therapy for treating menopausal symptoms and preventing osteoporosis, including the use of MPA in combination with conjugated estrogens 4.
• MPA has also been compared to other progestogens, such as norethindrone acetate (NETA) and dydrogesterone (DYD), in terms of its efficacy and safety in MHT 3.
• The choice of MPA as a progestogen in MHT should be individualized, taking into account the risk/benefit profile and tolerability of therapy, as well as patient preferences 4, 6.

Efficacy and Safety of Medroxyprogestterone

• The efficacy and safety of MPA in MHT have been evaluated in several clinical trials, with results showing that it is effective in reducing endometrial hyperplasia and vaginal bleeding 5, 7.
• However, the use of MPA in MHT has also been associated with an increased risk of breast cancer and cardiovascular events, particularly when used in combination with conjugated estrogens 4.
• A study published in 1989 found that continuous daily oral micronized estradiol and progesterone was effective in reducing vasomotor symptoms and vaginal atrophy in postmenopausal women, with minimal side effects and no endometrial hyperplasia 7.
• The safety and efficacy of MPA in MHT should be carefully evaluated, taking into account the individual patient's risk factors and medical history 3, 4, 6.

Comparison with Other Progestogens

• MPA has been compared to other progestogens, such as NETA and DYD, in terms of its efficacy and safety in MHT 3.
• A study published in 2015 found that conjugated estrogens combined with the selective estrogen receptor modulator bazedoxifene (BZA) was a effective and well-tolerated alternative to MPA in postmenopausal women with a uterus 6.
• The choice of progestogen in MHT should be individualized, taking into account the risk/benefit profile and tolerability of therapy, as well as patient preferences 4, 6.