From the FDA Drug Label
PATIENT INFORMATION Progesterone, USP Capsules 100 mgCapsules 200 mg Rx only Protection of the Endometrium (Lining of the Uterus) Progesterone, USP 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).
The FDA drug label does not directly answer the question of whether transdermal topical progesterone cream protects the endometrium in women treated with estrogen replacement therapy. The provided text only discusses the use of progesterone capsules, not transdermal topical progesterone cream, in combination with estrogen-containing medications for the protection of the endometrium 1, 1.
Key points:
- The use of progesterone capsules in combination with estrogen-containing medications reduces the risk of endometrial hyperplasia.
- There is no direct information on the use of transdermal topical progesterone cream for this purpose.
- The FDA drug label does not provide sufficient information to determine the effectiveness of transdermal topical progesterone cream in protecting the endometrium in women treated with estrogen replacement therapy.
From the Research
Transdermal topical progesterone cream does not reliably protect the endometrium in women treated with estrogen replacement therapy (ERT). Women taking systemic estrogen who have an intact uterus require adequate progestogen protection to prevent endometrial hyperplasia and cancer. While topical progesterone creams are available over-the-counter, they do not consistently achieve sufficient blood levels to provide endometrial protection, as evidenced by a study published in 2005 2. This study found that 32% of women had evidence of inadequate endometrial opposition after using transdermal natural progesterone cream and transdermal oestradiol for 48 weeks.
Key Points to Consider
- The dose of natural progesterone cream used in the study was insufficient to fully attenuate the mitogenic effect of oestrogen on the endometrium 2.
- Standard practice requires using FDA-approved progestogens such as oral micronized progesterone or synthetic progestins like medroxyprogesterone acetate.
- The inadequacy of topical progesterone creams stems from their variable absorption and insufficient systemic levels.
- Women using ERT with an intact uterus should use proven progestogen formulations prescribed by their healthcare provider rather than relying on over-the-counter progesterone creams for endometrial protection.
- A more recent study from 2019 3 suggests that levonorgestrel intrauterine devices may be an effective alternative for endometrial protection, but this does not support the use of transdermal topical progesterone cream.
Clinical Implications
The use of transdermal topical progesterone cream for endometrial protection in women treated with ERT is not supported by the evidence. Instead, women should use proven progestogen formulations prescribed by their healthcare provider to prevent endometrial hyperplasia and cancer. This is in line with the findings of studies published in 2005 2, 2007 4, and 2014 5, which highlight the importance of adequate progestogen protection for women with an intact uterus using ERT.