Progesterone has little effect on protein metabolism. It stimulates lipoprotein lipase activity and seems to favor fat deposition. The effects on carbohydrate metabolism are more marked. Progesterone increases basal insulin levels and the insulin response to glucose. There is usually no manifest change in carbohydrate tolerance. In the liver, progesterone promotes glycogen storage, possibly by facilitating the effect of insulin. Progesterone also promotes ketogenesis.
Progesterone can compete with aldosterone for the mineralocorticoid receptor of the renal tubule, causing a decrease in Na+ reabsorption. This leads to an increased secretion of aldosterone by the adrenal cortex (eg, in pregnancy). Progesterone increases body temperature in humans. The mechanism of this effect is not known, but an alteration of the temperature-regulating centers in the hypothalamus has been suggested. Progesterone also alters the function of the respiratory centers. The ventilatory response to CO2 is increased by progesterone but synthetic progestins with an ethinyl group do not have respiratory effects. This leads to a measurable reduction in arterial and alveolar Pco2 during pregnancy and in the luteal phase of the menstrual cycle. Progesterone and related steroids also have depressant and hypnotic effects on the brain.
Progesterone is responsible for the alveolobular development of the secretory apparatus in the breast. It also participates in the preovulatory LH surge and causes the maturation and secretory changes in the endometrium that are seen following ovulation (Figure 40–1).
Progesterone decreases the plasma levels of many amino acids and leads to increased urinary nitrogen excretion. It induces changes in the structure and function of smooth endoplasmic reticulum in experimental animals.
Other effects of progesterone and its analogs are noted below in the section, Hormonal Contraception.
C. Synthetic Progestins
The 21-carbon progesterone analogs antagonize aldosteroneinduced sodium retention (see above). The remaining compounds (“19-nortestosterone” third-generation agents) produce a decidual change in the endometrial stroma, do not support pregnancy in test animals, are more effective gonadotropin inhibitors, and may have minimal estrogenic and androgenic or anabolic activity (Table 40–2; Figure 40–4). They are sometimes referred to as “impeded androgens.” Progestins without androgenic activity include desogestrel, norgestimate, and gestodene. The first two of these compounds are dispensed in combination with ethinyl estradiol for oral contraception (Table 40–3) in the United States.
TABLE 40–3 Some oral and implantable contraceptive agents in use.1
TABLE 40–3 Some oral and implantable contraceptive agents in use.1 (Continued) 1The estrogen-containing compounds are arranged in order of increasing content of estrogen. Other preparations are available. (Ethinyl estradiol and mestranol have similar potencies.)
Oral contraceptives containing the progestin cyproterone acetate (also an antiandrogen) in combination with ethinyl estradiol are investigational in the United States.
A. Therapeutic Applications