Due to its antigonadotropic effects, norethisterone suppresses gonadal sex hormone production, inhibits ovulation in women, and suppresses spermatogenesis in men.The ovulation-inhibiting dosage of both oral norethisterone and oral NETA is about 0.5 mg/day in women. However, some conflicting data exist, suggesting that higher doses might be necessary for full inhibition of ovulation. An intramuscular injection of 200 mg NETE has been found to prevent ovulation and suppress levels of estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in women.Early studies of oral norethisterone in men employing doses of 20 to 50 mg/day observed suppression of 17-ketosteroid excretion, increased estrogen excretion (due to conversion into ethinylestradiol), suppression of spermatogenesis, libido, and erectile function, and incidence of gynecomastia. A dosage of oral norethisterone of 25 mg/day for 3 weeks in men has been reported to suppress testosterone levels by about 70%, to 100 to 200 ng/dL, within 4 or 5 days, as well as to suppress sperm count and to have no effect on libido or erectile function over this short time period. In healthy young men, NETA alone at a dose of 5 to 10 mg/day orally for 2 weeks suppressed testosterone levels from ~527 ng/dL to ~231 ng/dL (–56%). A single 200 mg intramuscular injection of NETE alone or in combination with 2 mg estradiol valerate has been found to produce a rapid, strong, and sustained decrease in gonadotropin and testosterone levels for up to one month in men.
Maternal androgenic symptoms occurred most often in women who received a dosage of norethisterone of 30 mg/day or more for a period of 15 weeks or longer. In the female infants who experienced virilization of the genitals, the sole manifestation in 86.7% of the cases was varied but almost always slight enlargement of the clitoris. In the remaining 13.3% of the affected cases, marked clitoral enlargement and partial fusion of the labioscrotal folds occurred. The dosages used in these cases were 20 to 40 mg/day.In a letter to the editor on the topic of virilization caused by high dosages of NETA in women, a physician expressed that they had not observed the "slightest evidence of virilization" and that there had "certainly been no hirsutism nor any voice changes" in 55 women with advanced breast cancer that they had treated with 30 to 60 mg/day norethisterone for up to six months.High-dosage norethisterone has been used to suppress menstruation in women with severe intellectual disability who were incapable of handling their own menses. A study of 118 nulliparous women treated with 5 mg/day norethisterone for a period of 2 to 30 months found that the drug was effective in producing amenorrhea in 86% of the women, with breakthrough bleeding occurring in the remaining 14%. Side effects including weight gain, hirsutism, acne, headache, nausea, and vomiting all did not appear to increase in incidence and no "disturbing side effects" were noted in any of the women.