Gestrinone is a 19-nortestosterone derivative with androgenic, antiprogestagenic, antiestrogenic, and antigonadotropic properties. It acts centrally and peripherally to increase free testosterone and reduce sex hormone–binding globulin levels (androgenic effect), reduce serum estradiol values to early follicular phase levels (antiestrogenic effect), reduce mean LH levels, and obliterate the LH and follicle-stimulating hormone (FSH) surge (antigonadotropic effect). Gestrinone causes cellular inactivation and degeneration of endometriotic implants but not their disappearance (388). Amenorrhea occurs in 50% to 100% of women and is dose dependent.
Resumption of menses generally occurs 33 days after discontinuing the medication (389,390). An advantage of gestrinone is its long half-life (28 hours) when given orally. The standard dose is 2.5 mg twice a week. Although 1.25 mg twice weekly is effective, a randomized study demonstrated in women with mild to moderate endometriosis that 2.5 mg gestrinone twice weekly for 24 weeks is more effective and has a better effect on bone mass (+7% vs. −7%) when compared with 1.25 mg gestrinone twice weekly for 24 weeks (391). The clinical side effects of gestrinone are dose dependent and similar to but less intense than those caused by danazol (391). They include nausea, muscle cramps, and androgenic effects such as weight gain, acne, seborrhea, and oily hair and skin.
In a multicenter, randomized, double-blind study, gestrinone was as effective as GnRH for the treatment of pelvic pain associated with endometriosis, with fewer side effects and the added advantage of twice-weekly administration (392). Pregnancy is contraindicated while taking gestrinone because of the risk for masculinization of the fetus.
Recognized pharmacologic properties of danazol include suppression of GnRH or gonadotropin secretion, direct inhibition of steroidogenesis, increased metabolic clearance of estradiol and progesterone, direct antagonistic and agonistic interaction with endometrial androgen and progesterone receptors, and immunologic attenuation of potentially adverse reproductive effects (98,393). The multiple effects of danazol produce a high-androgen, low-estrogen environment (estrogen levels in the early follicular to postmenopausal range) that does not support the growth of endometriosis, and the amenorrhea that is produced prevents new seeding of implants from the uterus into the peritoneal cavity.