Progestogen

Steroidogenesis, with progestagens inside yellow box.

Progestogens (also spelled progestagens or gestagens) are a group of hormones including progesterone. The progestogens are one of the five major classes of steroid hormones, in addition to the estrogens, androgens, mineralocorticoids, and glucocorticoids. All progestogens are characterized by their basic 21-carbon skeleton, called a pregnane skeleton (C21). In similar manner, the estrogens possess an estrane skeleton (C18) and androgens, an andrane skeleton (C19).

Progestogens are named for their function in maintaining pregnancy (pro-gestational), although they are also present at other phases of the estrous and menstrual cycles. The progestogen class of hormones includes all steroids with a pregnane skeleton, that is, both naturally occurring and synthetic ones. Exogenous or synthetic hormones are usually referred to as progestins.

Functions

Progestogens as precursors to other steroids

In the first step in the steroidogenic pathway, a cholesterol molecule is converted into pregnenolone (P5). P5 and other members of the progestogen class of steroids serve as precursors to all other steroids, including the estrogens, androgens, mineralocorticoids, and glucocorticoids. P5, P4, 17α-hydroxypregnenolone, and 17α-hydroxyprogesterone are all endogenously produced intermediates in the pathway. Thus, all tissues producing steroids, such as the adrenals, ovaries, and testes, must be capable of producing progestogens.

In some tissues, the enzymes required for the final product are not all located in a single cell; for example, in ovarian follicles, cholesterol is converted to androstenedione, an androgen, in the theca cells, which is further converted into estrogen in the granulosa cells. Fetal adrenal glands also produce P5 in some species, which is converted into P4 and estrogens by the placenta (see below). In the human, the fetal adrenals produce dihydroepiandrosterone via the P5 pathway.

Progestogen production by the ovary

Progesterone (P4) is the major progestogen produced by the corpus luteum in all mammalian species. Luteal cells possess the necessary enzymes to convert cholesterol to pregnenolone (P5), which is subsequently converted into P4. P4 is highest in the diestrus phase of the estrous cycle.

Progestogen production by the placenta

The role of the placenta in progestogen production varies by species. In the sheep, horse, and human, the placenta takes over the majority of progestogen production, whereas in other species the corpus luteum remains the primary source of progestogen. In the sheep and human, P4 is the major placental progestogen.

The equine placenta produces a variety of progestogens, primarily 5αDHP and 20α5P, beginning on day 60. A complete luteo-placental shift occurs by day 120-150.

Uses

Birth control

Main article: Hormonal contraception

Progestins, synthetic substances with progestagenic activity are used in birth control pills, implants and the intrauterine system IUS (Mirena).

Antiandrogen

Main article: Antiandrogen

The synthetic progestin cyproterone is used as antiandrogen. Various other progestins have androgenic properties.

Progesterone withdrawal bleeding

In a normal menstrual cycle, declining levels of progesterone triggers menstruation. Norethindrone acetate (brand name Aygestin) and medroxyprogesterone acetate (brand name Provera) may be used to artificially induce progestogen withdrawal bleeding.^{[citation needed]}

Cachexia Syndrome

Further information: Cachexia

In many people suffering from solid malignancy, especially gastric and pancreatic cancer, progestins can be employed to improve appetite and reduce wasting. In general, they are used in combination with other steroids such as dexamethasone. Their effects take several weeks to become apparent, but are relatively long-lived when compared to those of corticosteroids. Furthermore, they are recognized as being the only drugs to increase lean body mass. Megestrol acetate is the lead drug of this class for the management of cachexia.

External links

• The Nomenclature of Steroids
• The Million Women Study
• Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH (June 2001). "Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate". Fertil. Steril. 75 (6): 1065–79. doi:10.1016/S0015-0282(01)01791-5. PMID 11384629. http://linkinghub.elsevier.com/retrieve/pii/S0015-0282(01)01791-5.  (the Women's Health, Osteoporosis, Progestin, Estrogen study)
• Hulley S, Grady D, Bush T, et al. (August 1998). "Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group". JAMA 280 (7): 605–13. doi:10.1001/jama.280.7.605. PMID 9718051. http://jama.ama-assn.org/cgi/content/full/280/7/605.