How to induce menstruation with estrogen therapy followed by progesterone (progestin) treatment?

From the Guidelines

To induce a period with estrogen followed by progesterone, the recommended approach is to take estrogen for 21-25 days, followed by progesterone for the last 10-14 days of the estrogen course, with a common regimen being micronized progesterone (MP) at 100-200 mg daily for 12-14 days every 28 days, as it has a safer pharmacological profile compared to synthetic progestogens 1.

Estrogen Component

The estrogen component can be administered using various formulations, including transdermal 17β-estradiol, oral 17β-estradiol, or oral ethinylestradiol, with suggested dosages varying based on the time elapsed after pubertal induction start, as outlined in Table 3 of the study by 1.

• For example, for the first 6 months, transdermal 17β-estradiol can be started at 1/8 of a patch all week, while oral 17β-estradiol can be started at 0.5 mg every other day.
• Estrogen doses should be increased not earlier than 6-monthly over a period of 24 months, with both periodical clinical assessment of secondary sexual features and ultrasonographic evaluation of uterine volume and morphology guiding dose escalation 1.

Progesterone Component

For the progesterone phase, micronized progesterone (MP) at 100-200 mg daily for 12-14 days every 28 days is recommended due to its physiological and safe profile 1.

• Alternative options include medroxyprogesterone acetate (MPA) at 5-10 mg daily or norethisterone at 5 mg daily, administered for 12-14 days every 28 days, although MP is considered the first choice due to its favorable safety profile 1.
• The choice between a sequential and continuous regimen of administration should be based on the individual patient's needs, with the cyclic administration allowing for earlier recognition of pregnancy 1.

Important Considerations

Before starting any hormonal therapy, it is essential to consult with a healthcare provider to rule out pregnancy and other contraindications, and to monitor for potential side effects such as breast tenderness, nausea, headaches, and mood changes 1.

• Additionally, sonographic evaluation may be advised before prescribing progestin to demonstrate proper endometrial thickness and minimize the risk of endometrial hyperplasia 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. Administration should be cyclic (e.g., 3 weeks on and 1 week off).

To induce a period with estrogen followed by progesterone, estrogen should be administered for a certain period, typically 3 weeks, followed by progesterone to reduce the risk of endometrial cancer in women with a uterus. The lowest effective dose of estrogen should be used, and the regimen should be cyclic. However, the exact dosage and duration for inducing a period are not explicitly stated in the provided drug labels. 2

From the Research

Inducing a Period with Estrogen Followed by Progesterone

To induce a period with estrogen followed by progesterone, the following steps can be considered:

• Estrogen is introduced to the body, which can be done through various forms such as patches, pills, or injections 3.
• After a certain period of estrogen introduction, progesterone is added to the regimen. This can be done in a cyclic or continuous manner, depending on the individual's needs and medical history 3, 4.
• The dosage and duration of estrogen and progesterone treatment can vary depending on the individual's response and medical goals. For example, lower doses of estrogen may be used to minimize side effects, while higher doses may be used to achieve specific therapeutic effects 3, 5.
• The type of progesterone used can also impact the treatment outcome. Different progestogens, such as micronized progesterone, medroxyprogesterone acetate, and norethindrone acetate, have distinct properties and effects on the body 4, 6, 7.
• The regimen can be tailored to minimize side effects, such as bleeding, and maximize therapeutic benefits. For example, a cyclic regimen with lower doses of estrogen and progesterone may be used to minimize bleeding and side effects, while a continuous combined regimen may be used to simplify the treatment and reduce bleeding 3, 5.

Key Considerations

• The introduction of estrogen followed by progesterone can stimulate the endometrium and induce a period-like bleeding 3, 5.
• The choice of progesterone and regimen type can impact the treatment outcome and side effects 4, 6, 7.
• Individualized treatment plans should be developed based on the individual's medical history, needs, and response to treatment 3, 5.