When to increase estriol (estrogen) and progesterone doses?

When to Increase Estriol and Progesterone Doses

Progesterone doses should be increased when using a sequential regimen with estrogen therapy, particularly when administered for 12-14 days per month in patients with premature ovarian insufficiency or those requiring endometrial protection. 1

Progesterone Dosing Guidelines

• Standard adult doses in sequential regimens include 200 mg of oral or vaginal micronized progesterone for 12-14 days every 28 days 1
• For continuous regimens (when patients prefer to avoid withdrawal bleeding), progesterone is administered without interruption alongside estrogen 1
• Micronized progesterone is the preferred choice among progestins due to its lower risk of cardiovascular disease, venous thromboembolism, and better safety profile regarding metabolic effects and breast cancer risk 1

Indications for Dose Adjustments

Increase Progesterone When:

• Endometrial hyperplasia is detected or suspected (progesterone at 200 mg/day for 12 days per 28-day cycle with conjugated estrogens has shown only 6% hyperplasia rate versus 64% with estrogen alone) 2
• Secondary amenorrhea persists despite initial therapy (increasing from 300 mg to 400 mg daily for 10 days may improve withdrawal bleeding rates from 73.8% to 76.8%) 2
• Secretory transformation rates are inadequate (increasing to 400 mg daily can improve complete secretory transformation rates from 21.5% to 28.3%) 2

Increase Estriol When:

• Inadequate response to initial therapy is observed in postmenopausal women (both vaginal estriol and estradiol therapies show similar biochemical and histological signs of estrogenic stimulation) 3
• Maternal plasma progesterone levels need to be adjusted (rectal administration of 100 mg estriol can cause approximately 20% decrease in plasma progesterone levels) 4

Monitoring Parameters for Dose Adjustments

• For women with cyclic attacks related to acute hepatic porphyrias, measure serum progesterone at onset of symptoms to identify luteal phase and potentially progesterone-induced attacks 5
• Monitor endometrial response through histological assessment when adjusting doses (complete secretory changes in the endometrium occur in 45% of women with 400 mg/day progesterone versus 0% with placebo) 2
• Assess withdrawal bleeding patterns when adjusting doses in premenopausal women with secondary amenorrhea 2

Cautions and Contraindications

• Avoid hormone therapy with estrogen plus progestin in postmenopausal women after ST-elevation myocardial infarction for secondary prevention of coronary events 5
• Women already taking estrogen plus progestin at the time of ST-elevation myocardial infarction should not continue hormone therapy 5
• Be cautious with progestins that have anti-androgenic effects in patients with premature ovarian insufficiency who may already suffer from diminished libido or impaired sexual function 1

Special Populations

• For women with cyclic attacks related to acute hepatic porphyrias, consider GnRH analogues, low-dose hormonal contraceptives, or prophylactic hemin infusions rather than increasing progesterone 5
• In women with singleton gestations and prior spontaneous preterm birth, 17P 250 mg IM weekly starting at 16-20 weeks until 36 weeks is recommended, but dose adjustments based on response are not specifically indicated 5

Remember that hormone therapy decisions should prioritize the lowest effective doses for the shortest duration consistent with treatment goals and individual risk factors 5.