Progesterone and is responsible for approximately 70% of cytochrome P450-mediated progesterone metabolism. Other routes include 6α-, 16α-, and 16β-hydroxylation. However, treatment of women with ketoconazole, a strong CYP3A4 inhibitor, had minimal effects on progesterone levels, producing only a slight and non-significant increase, and this suggests that cytochrome P450 enzymes play only a small role in progesterone metabolism. In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase, as shown in diagram below. Progesterone levels tend to be less than 2 ng/mL prior to ovulation, and greater
Topical progesterone of tissue exposure to progesterone with this route of administration. These findings provide a possible explanation for how some studies found antiproliferative and atrophic changes in the endometrium with topical progesterone. However, elevated levels of progesterone in the endometrium with topical progesterone have not yet been demonstrated. Concern has been raised regarding topical progesterone in that the effects of such supraphysiological levels of progesterone in tissues are unknown and hence the potential for harmful effects has not been ruled out. Salivary monitoring of progesterone levels in women using topical progesterone and adjustment of dosage as necessary has been suggested as