What is the target progesterone level in a postmenopausal woman on estrogen and progesterone (hormone) replacement therapy?

Target Progesterone Levels in Postmenopausal Women on HRT

There is no specific target progesterone level that needs to be monitored in postmenopausal women on estrogen and progesterone replacement therapy. Instead, the adequacy of progesterone therapy is determined by clinical outcomes such as endometrial protection and bleeding patterns.

Progesterone Dosing in HRT

The American College of Obstetricians and Gynecologists recommends the following progesterone regimens for women with an intact uterus on estrogen therapy 1:

• Oral micronized progesterone: 200 mg for 12-14 days per month in a sequential regimen
• Continuous regimens: Minimum of 100 mg daily of oral micronized progesterone

Alternative progestin options include:

• Medroxyprogesterone acetate: 2.5 mg/day (continuous) or 10 mg for 12-14 days per month (sequential)
• Dydrogesterone: 5 mg daily (continuous) or 10 mg for 12-14 days per month (sequential)
• Norethisterone: 1 mg daily (continuous)

Clinical Indicators of Adequate Progesterone Effect

Rather than monitoring serum progesterone levels, clinicians should assess:

1. Endometrial Protection: The primary purpose of progesterone in HRT is to prevent estrogen-induced endometrial hyperplasia. Adequate progesterone dosing results in secretory transformation of the endometrium 2.

2. Bleeding Patterns: A practical clinical indicator of adequate progesterone effect is the timing of withdrawal bleeding:

   • Bleeding on or before day 10 after starting progesterone suggests inadequate progesterone effect (predominantly proliferative endometrium)
   • Bleeding on day 11 or later indicates adequate progesterone effect (secretory endometrium) 2

3. Endometrial Thickness: Transvaginal ultrasound can be used to monitor endometrial thickness, with thickness <5mm generally considered reassuring 3.

Route of Administration Considerations

• Oral micronized progesterone at 300 mg has shown 58.9% improvement in vasomotor symptoms versus 23.5% with placebo 4.
• Vaginal progesterone can achieve adequate endometrial protection at lower doses:
  • 45-90 mg every 48 hours has been shown to produce secretory endometrial transformation 5
  • Crinone 4% (45 mg) applied vaginally daily for 10 days per month or twice weekly in continuous regimens effectively protects the endometrium 3

Common Pitfalls to Avoid

1. Inadequate progesterone dosing: Insufficient progesterone fails to protect against endometrial hyperplasia.

2. Excessive progesterone dosing: May cause side effects like headaches and breakthrough bleeding, leading to discontinuation in 6-21% of patients 4.

3. Ignoring bleeding patterns: Irregular or heavy bleeding should prompt evaluation for endometrial pathology.

4. Focusing on serum levels: Serum progesterone levels do not reliably reflect endometrial effect, especially with vaginal administration which achieves high uterine concentrations despite lower serum levels.

5. Continuing HRT after acute cardiovascular events: HRT should be discontinued if a woman develops an acute cardiovascular event 6.

Remember that HRT is not recommended for women over 65 years old due to increased risks of stroke, dementia, and venous thromboembolism that outweigh potential benefits 1.