5α-Reductase inhibitors such as finasteride and dutasteride inhibit the conversion of progesterone into the inhibitory neurosteroid allopregnanolone, and for this reason, may have the potential to reduce the sedative and related effects of progesterone.Progesterone is a weak but significant agonist of the pregnane X receptor (PXR), and has been found to induce several hepatic cytochrome P450 enzymes, such as CYP3A4, especially when concentrations are high, such as with pregnancy range levels. As such, progesterone may have the potential to accelerate the metabolism of various medications. Pharmacology
Pharmacodynamics
Progesterone is a progestogen, or an agonist of the nuclear progesterone receptors (PRs), the PR-A, PR-B, and PR-C. In addition, progesterone is an agonist of the membrane progesterone receptors (mPRs), including the mPRα, mPRβ, mPRγ, mPRδ, and mPRϵ. Aside from the PRs and mPRs, progesterone is a potent antimineralocorticoid, or antagonist of the mineralocorticoid receptor, the biological target of the mineralocorticoid aldosterone. In addition to its activity as a steroid hormone, progesterone is a neurosteroid. Among other neurosteroid activities, and via its active metabolites allopregnanolone and pregnanolone, progesterone is a potent positive allosteric modulator of the GABAA receptor, the major signaling receptor of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).The PRs are expressed widely throughout the body, including in the uterus, cervix, vagina, fallopian tubes, breasts, fat, skin, pituitary gland, hypothalamus, and in other areas of the brain. In accordance, progesterone has numerous effects throughout the body. Among other effects, progesterone produces changes in the female reproductive system, the breasts, and the brain.
Although not sufficiently powered, various other smaller studies have also found endometrial protection with oral or vaginal progesterone. There is inadequate evidence for endometrial protection with transdermal progesterone cream.Oral progesterone has been found to significantly reduce hot flashes relative to placebo. The combination of an estrogen and oral progesterone likewise reduces hot flashes. Estrogen plus oral progesterone has been found to significantly improve quality of life. The combination of an estrogen and 100 to 300 mg/day oral progesterone has been found to improve sleep outcomes. Moreover, sleep was improved to a significantly better extent than estrogen plus medroxyprogesterone acetate. This may be attributable to the sedative neurosteroid effects of progesterone. Reduction of hot flashes may also help to improve sleep outcomes. Based on animal research, progesterone may be involved in sexual function in women. However, very limited clinical research suggests that progesterone does not improve sexual desire or function in women.The combination of an estrogen and oral progesterone has been found to improve bone mineral density (BMD) to a similar extent as an estrogen plus medroxyprogesterone acetate. Progestogens, including progesterone, may have beneficial effects on bone independent of those of estrogens, although more research is required to confirm this notion. The combination of an estrogen and oral or vaginal progesterone has been found to improve cardiovascular health in women in early menopause but not in women in late menopause. Estrogen therapy has a favorable influence on the blood lipid profile, which may translate to improved cardiovascular health.