Danazol has progestin-like actions on the human endometrium

Area of Science:

• Reproductive Endocrinology
• Pharmacology

Background:

• Endometrial receptivity is crucial for implantation.
• Hormonal regulation of the endometrium involves estrogen and progesterone.

Purpose of the Study:

• To investigate the endometrial actions of danazol.
• To compare danazol's effects with medroxyprogesterone acetate.
• To elucidate the mechanism of danazol's therapeutic effect.

Main Methods:

• Administration of danazol (200 mg TID) or medroxyprogesterone acetate (100 mg daily) to normally menstruating women.
• Measurement of endometrial cytosol estrogen and progestin receptor concentrations.
• Assay of 17 beta-hydroxysteroid dehydrogenase activity.
• Quantification of serum gonadotrophins, estradiol, and progesterone.

Main Results:

• Danazol significantly reduced endometrial cytosol estrogen and progestin receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activity.
• Medroxyprogesterone acetate produced similar endometrial changes.
• Danazol suppressed luteal serum estradiol and progesterone but not gonadotrophins.
• In vitro studies showed danazol binds to the endometrial progestin receptor with 3% affinity of progesterone.

Conclusions:

• Danazol exerts its therapeutic effect through a local progestin-like action on the endometrium.
• This local action may be enhanced by the suppression of circulating estradiol levels.
• Danazol's endometrial effects are comparable to medroxyprogesterone acetate.