on the HPG axis Antigonadotropic effects Progestogens have antigonadotropic effects at sufficiently high doses via activation of the PR and consequent negative feedback on and hence suppression of the hypothalamic–pituitary–gonadal axis (HPG axis). This results in suppression of gonadotropin secretion and by extension interference with fertility and gonadal sex hormone production. Progesterone prevents ovulation by suppressing the mid-cycle surge in gonadotropin secretion during the menstrual cycle. The ovulation-inhibiting (i.e., contraceptive) dosage of oral crystalline (non-micronized) progesterone in women is 300 mg/day or greater. However, this figure is based on limited clinical data. In the clinical research in the 1950s that determined this dosage, ovulation inhibition occurred in 50 to 100% of women when assessed via measures including urinary pregnanediol excretion, daily basal body temperatures, endometrial biopsies, and vaginal smears. Another study found that ovulation inhibition with 300 mg/day oral non-micronized progesterone occurred in a "proportion of the cases" when assessed via laparotomy. A third study found that ovulation was inhibited in only 38% of women treated with 1,000 mg/day oral non-micronized progesterone. A fourth publication stated that even 750 to 1,000 mg/day oral non-micronized progesterone had weak effects as evidenced by poor thermogenic effect, weak endometrial effect, and lack of production of withdrawal bleeding in amenorrheic women. Neumann and colleagues listed the ovulation-inhibiting dosage of oral non-micronized progesterone in women as 300 to 500 mg/day or as 400 mg/day but provided no other details. In a study of a progesterone vaginal ring alone or in combination with estradiol that released 1.5 to 3 mg/day progesterone and achieved mean progesterone levels varying between 0.7 and 1.6 ng/mL (mean 0.9 ng/mL) during anovulatory cycles, ovulation occurred in 18 of 30 (60%) menstrual cycles. A study of a vaginal progesterone ring that released almost 10 mg/day progesterone and maintained mean progesterone levels of 4.4 ng/mL (range 2.4–6.5 ng/mL) found that ovulation was inhibited in some but not all women. In another study, a progesterone vaginal ring that released about 10 mg/day progesterone and produced progesterone levels of around 4 ng/mL (range 3–5.2 ng/mL) resulted in ovulation occurring in 25% of treated breastfeeding women compared to a rate of 56% in a control group of breastfeeding women. A study in rhesus monkeys found that a vaginal ring delivering 0.235 or 1.77 mg/day progesterone inhibited ovulation in all monkeys at the higher dose and in a proportion of monkeys at the lower dose. A dose