The impact of micronized progesterone on cardiovascular events - a systematic review.

Biologically identical menopausal hormone therapy (MHT) including micronized progesterone (MP) has gained much attention. We aimed to assess the impact of MP in combined MHT on venous and arterial thromboembolism (VTE/ATE) (e.g. deep venous thrombosis/pulmonary embolism, myocardial infarction [MI] and ischemic stroke). Articles were eligible if they provided endpoints regarding cardiovascular events and use of exogenous MP. Literature searches were designed and executed for the databases Medline, Embase, CINAHL, the Cochrane Library, ClinicalTrials.gov and interdisciplinary database Web of Science. Twelve studies consisting of randomized controlled trials (RCTs), case-control studies and prospective or retrospective cohort studies were included, and risk of bias was assessed. Only a minority assessed thromboembolic events as a primary endpoint, showing that in contrast to norpregnane derivatives, primary and recurrent VTE risk was not altered by combining estrogens with MP, which was also true for ischemic stroke risk. Similarly, in placebo-controlled RCTs assessing VTE/ATE as adverse events there were no significant intergroup differences. Studies on MI as a primary endpoint are missing. In conclusion, while available data suggest that MP as a component in combined MHT may have a neutral effect on the vascular system, more RCTs investigating the impact of MP alone or in combined MHT on vascular primary endpoints are needed.

The impact of micronized progesterone on breast cancer risk: a systematic review.

Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including micronized progesterone has increased in recent years. Based on a systematic literature review on the impact of menopausal hormone therapy (MHT) containing micronized progesterone on the mammary gland, an international expert panel's recommendations are as follows: (1) estrogens combined with oral (approved) or vaginal (off-label use) micronized progesterone do not increase breast cancer risk for up to 5 years of treatment duration; (2) there is limited evidence that estrogens combined with oral micronized progesterone applied for more than 5 years are associated with an increased breast cancer risk; and (3) counseling on combined MHT should cover breast cancer risk - regardless of the progestogen chosen. Yet, women should also be counseled on other modifiable and non-modifiable breast cancer risk factors in order to balance the impact of combined MHT on the breast.

The impact of micronized progesterone on the endometrium: a systematic review.

Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. International guidelines on menopausal hormone therapy (MHT) do not specify on progestogen type, dosage, route of application and duration of safe use. At the same time, the debate on bioidentical hormones including micronized progesterone increases. Based on a systematic literature review on micronized progesterone for endometrial protection, an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal micronized progesterone does not provide endometrial protection.