Progestogens[1] (also spelled progestagens[2] 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.[2] Exogenous or synthetic hormones are usually referred to as progestins.
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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.
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.
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.
Progestinic compounds decrease luteinizing hormone (LH) levels[3] and, as such, will have antiandrogenic properties in trans-women and males alike, due to decreased LH stimulation of the testes. Cyproterone is a common example of a progestinic medication, and is an effective antiandrogen, which has the added benefit of blocking androgen receptors in addition to the progestinic feedback to decrease LH levels.
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.
In many people suffering from solid malignancy, especially gastric and pancreatic cancer, progestogens 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.
Adverse effects of progestogens include weak androgenic actions, acne, fluid retention, weight changes, depression, change in libido, breast discomfort, premenstrual syndrome, irregular menstrual cycles, and breakthrough bleeding.[4] Also, there is an increased risk of thromboembolism. [4]
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