From the Guidelines
I strongly advise against using a topical compounded preparation of 100 mg progesterone with estradiol daily for HRT without consulting a healthcare provider, as the safety and efficacy of this formulation are unknown and may vary widely between individuals. The use of hormone replacement therapy (HRT) should be individualized based on a woman's specific symptoms, age, medical history, and hormone levels, as well as her personal preferences and risk factors for certain chronic diseases 1. Standard HRT typically uses oral micronized progesterone (100-200 mg daily) or FDA-approved transdermal preparations, which have been studied extensively and have known efficacy and safety profiles. Some key points to consider when determining the appropriate HRT regimen include:
- The need for progesterone to protect the uterine lining from estrogen-stimulated overgrowth in women with a uterus
- The choice between cyclic and continuous progesterone regimens, depending on the individual's symptoms and medical history
- The importance of monitoring hormone levels and adjusting the dose as needed to minimize side effects and maximize benefits
- The potential benefits and harms of HRT, including increased bone mineral density and reduced risk of fracture, as well as increased risk of breast cancer, venous thromboembolism, and coronary heart disease 1. Given the complexity of HRT and the potential for serious side effects, I recommend consulting with a healthcare provider experienced in menopause management to determine the best course of treatment for your individual needs.
From the FDA Drug Label
The treatment groups were: Progesterone Capsules at the dose of 200 mg per day for 12 days per 28-day cycle in combination with conjugated estrogens 0.625 mg per day
- Dose: The FDA drug label does not provide information on a dose of progesterone 100 mg topical compounded with estradiol daily for HRT.
- Route of administration: The label discusses oral progesterone capsules, not topical administration.
- Combination with estradiol: While the label mentions combination with conjugated estrogens, it does not specifically address estradiol or a topical formulation. The FDA drug label does not answer the question.
From the Research
HRT Regimens and Endometrial Hyperplasia
- The use of unopposed estrogen replacement therapy (ERT) is associated with an increased risk of endometrial hyperplasia and carcinoma 2, 3, 4, 5.
- Adding a progestogen to estrogen therapy can decrease or eliminate the endometrial risk associated with ERT 2, 3, 4, 5.
- Natural micronized progesterone can be used in lieu of synthetic progestins to alleviate side effects and improve tolerability 2.
Progesterone Dosage and Endometrial Safety
- A cyclic combined regimen comprising estrogen and 100 mg micronized progesterone administered on days 1-25 has been shown to provide endometrial safety, absence of bleeding, and a high rate of tolerability in European studies 2.
- However, the optimal dosage of progesterone required to prevent endometrial hyperplasia is not well established, and more research is needed to determine the minimum effective dose 5.
Topical Compounded HRT Regimens
- There is limited evidence on the use of topical compounded HRT regimens, including progesterone 100 mg topical compounded with estradiol daily 6.
- One study found that an estradiol/progesterone-releasing vaginal ring could prevent endometrial hyperplasia and relieve climacteric symptoms in postmenopausal women, but the progesterone dosage used was lower (20 mg/day or 10 mg/day) than the 100 mg topical dosage mentioned 6.
Key Considerations
- The addition of progestogen to estrogen therapy can help reduce the risk of endometrial hyperplasia, but the optimal dosage and regimen are not well established 3, 4, 5.
- More research is needed to determine the safety and efficacy of topical compounded HRT regimens, including progesterone 100 mg topical compounded with estradiol daily 6.