What is the role of Medroxyprogesterone (MPA) in postmenopause?

From the Guidelines

Medroxyprogesterone acetate should not be used for the primary prevention of chronic conditions in postmenopausal women due to its associated harms, including an increased risk of stroke, dementia, gallbladder disease, urinary incontinence, and invasive breast cancer. The use of medroxyprogesterone acetate, specifically in combination with oral conjugated equine estrogen, has been found to have moderate benefits in reducing the risk of fractures in postmenopausal women 1. However, these benefits are outweighed by the moderate harms associated with its use. The US Preventive Services Task Force found convincing evidence of a small increase in the incidence of invasive breast cancer and adequate evidence of a small increase in breast cancer deaths with the use of estrogen and progestin therapy 1. Additionally, there is convincing evidence that estrogen and progestin therapy is associated with a small increased risk for deep venous thrombosis and pulmonary embolism, and probably increases the risk for coronary heart disease 1.

When considering hormone therapy for postmenopausal women, it is essential to weigh the potential benefits against the risks and use the lowest effective dose for the shortest duration necessary. For women with an intact uterus, medroxyprogesterone acetate is typically used in combination with estrogen to prevent endometrial hyperplasia and reduce the risk of endometrial cancer. However, for women who have had a hysterectomy, estrogen alone may be considered, as it has been found to have a moderate benefit in reducing the incidence of fractures and a small reduction in the risk for developing or dying of invasive breast cancer 1.

Key considerations for the use of medroxyprogesterone acetate in postmenopausal women include:

• The potential benefits of fracture reduction and prevention of endometrial hyperplasia
• The associated harms, including increased risk of stroke, dementia, gallbladder disease, urinary incontinence, and invasive breast cancer
• The use of the lowest effective dose for the shortest duration necessary to minimize risks
• Alternative treatment options, such as estrogen alone for women who have had a hysterectomy, or non-hormonal therapies for the management of vasomotor symptoms and prevention of osteoporosis.

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 can be used in postmenopausal women to reduce the risk of endometrial hyperplasia when given in combination with estrogen. The recommended dosage is 5 or 10 mg daily for 12 to 14 consecutive days per month. The treatment should be started at the lowest dose, and patients should be re-evaluated periodically to determine if treatment is still necessary 2.

Key points:

• Medroxyprogesterone 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.
• Treatment should be started at the lowest dose and patients should be re-evaluated periodically.

From the Research

Medroxyprogesterone for Post-Menopause

• Medroxyprogesterone acetate (MPA) is used in combination with estrogen for hormone therapy in postmenopausal women to reduce the risk of endometrial hyperplasia 3, 4.
• The risk of endometrial hyperplasia with hormone therapy comprising low-dose estrogen continuously combined with a minimum of 1.5 mg MPA is not significantly different from placebo 3, 4.
• Hormone therapy for postmenopausal women with an intact uterus should comprise both estrogen and progestogen to reduce the risk of endometrial hyperplasia 3, 4.

Benefits and Harms of Hormone Therapy

• The use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with some benefits, but also with well-documented harms 5.
• The US Preventive Services Task Force recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women 5.
• The US Preventive Services Task Force also recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal women who have had a hysterectomy 5.

Progestogens for Endometrial Protection

• Medroxyprogesterone acetate (MPA) is one of the progestogens used in combined menopausal hormone therapy for endometrial protection 6.
• Most studies on progestogens for endometrial protection were done with norethisterone acetate (NETA), followed by MPA, and other progestogens 6.
• The most frequently studied progestogens, including MPA, were assessed in continuously as well as in sequentially combined MHT regimens 6.