What dose of progesterone would be used for a patient already receiving estrogen (oestrogen) for transgender hormone therapy?

From the Guidelines

For a patient already receiving estrogen for transgender therapy, a typical progesterone dose would be 100-200 mg of oral micronized progesterone daily, taken at bedtime, as it has a more favorable safety profile compared to synthetic progestins like medroxyprogesterone acetate 1. This dose should only be added after the patient has been on estrogen therapy for at least 6-12 months, as adding progesterone too early may interfere with optimal breast development. Some key points to consider when prescribing progesterone for transgender hormone therapy include:

• Oral micronized progesterone (Prometrium) is generally preferred over synthetic progestins like medroxyprogesterone acetate, as it may have a better side effect profile 1.
• The dose of progestogen is based on the concurrent dose of estrogen administered, and adult doses of oral progestin depend on the doses of estrogen administered 1.
• Progesterone may help with breast development, improve mood, and enhance libido in some patients, though evidence for its benefits in transgender care is largely anecdotal.
• Side effects can include drowsiness, dizziness, and mood changes, which is why bedtime dosing is recommended.
• Regular monitoring of hormone levels, liver function, and cardiovascular risk factors should continue after adding progesterone to the hormone regimen.
• The decision to add progesterone should be individualized based on the patient's goals, risk factors, and response to estrogen therapy. When prescribing HRT, clinicians should choose between a sequential and continuous regimen of administration, with the latter preventing withdrawal bleeding, and among progestins, MP is the first choice, indeed recent studies have reported that, if taken with cyclical administration, MP is associated with a lower risk of cardiovascular disease and venous thromboembolism and it determines endometrial protection 1.

From the FDA Drug Label

In a multicenter, parallel-group, open label postmarketing dosing study consisting of three consecutive 28­day treatment cycles, 220 premenopausal women with secondary amenorrhea were randomized to receive daily conjugated estrogens therapy (0. 625 mg conjugated estrogens) and progesterone capsules, 300 mg per day (n=113) or 400 mg per day (n=107) for 10 days of each treatment cycle A second multicenter, parallel-group, open label postmarketing dosing study in premenopausal women with secondary amenorrhea for at least 90 days also evaluated the rate of secretory transformation All subjects received daily oral conjugated estrogens over 3 consecutive 28-day treatment cycles and progesterone capsules, 300 mg per day (n=107) or 400 mg per day (n=99) for 10 days of each treatment cycle.

The dose of progesterone that would be used for a patient already receiving estrogen for transgender therapy is 300 mg per day or 400 mg per day for 10 days of each 28-day treatment cycle, in combination with daily conjugated estrogens therapy (0.625 mg conjugated estrogens) 2.

From the Research

Progesterone Dosage for Transgender Therapy

The ideal dose of progesterone for a patient already receiving estrogen for transgender therapy is not explicitly stated in the provided studies. However, the importance of progesterone in transgender women's therapy is highlighted in several studies:

• Progesterone is considered important for optimal transgender women's cross-sex hormone therapy, as it may add benefits such as more rapid feminization, decreased endogenous testosterone production, and optimal breast maturation 3.
• The addition of progesterone to estradiol and an antiandrogen in transgender women's cross-sex hormone therapy is recommended, as it may provide physiological benefits similar to those experienced by ciswomen 3.
• However, the provided studies do not specify a particular dose of progesterone that should be used in conjunction with estrogen therapy.

Considerations for Hormone Therapy

When considering hormone therapy for transgender patients, several factors should be taken into account:

• Cross-sex hormone therapy has been shown to have positive physical and psychological effects on transitioning individuals, but bone and cardiovascular health are important considerations in patients on long-term hormones 4.
• The use of certain estrogens in trans women may induce an increased risk of myocardial infarction and stroke, emphasizing the need for lifestyle management as an integral part of trans health care 5.
• The dosage of hormonal supplementation and stimulating therapy compliance are crucial, particularly for adolescent and adult trans women, to achieve adequate bone health 5.

Available Data and Research Gaps

The available data on hormone therapy for transgender patients are expanding, but there are still gaps in research:

• Many previous review papers have focused on all available data, but a more recent literature review is timely, as hormonal regimens have changed over time, and older data may be less relevant for today's practice 5.
• The observed cancer risk in trans people does not exceed the known cancer-risk differences between men and women, but more research is needed to fully understand the effects of hormone therapy on cancer risk 5.