| Progestogen | |
|---|---|
| Drug class | |
 Progesterone, the major progestogen in humans and a widely used medication. | |
| Class identifiers | |
| Synonyms | Progestins; Progestagens; Gestagens, |
| Use | Contraception,menopause,hypogonadism,transgender women, others |
| ATC code | G03D |
| Biological target | Progesterone receptors (PRA,PRB,PRC,mPRs (e.g.,mPRα,mPRβ,mPRγ,mPRδ, others)) |
| External links | |
| MeSH | D011372 |
| Legal status | |
| In Wikidata | |
Progestogens, also sometimes writtenprogestins,progestagens orgestagens,[1] are a class of natural or syntheticsteroid hormones that bind to and activate theprogesterone receptors (PR).[2][3]Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintainingpregnancy (i.e.,progestational), although they are also present at other phases of theestrous andmenstrual cycles.[2][3]
The progestogens are one of three types ofsex hormones, the others beingestrogens likeestradiol andandrogens/anabolic steroids liketestosterone. In addition, they are one of the five major classes of steroid hormones, the others being the androgens, estrogens,glucocorticoids, andmineralocorticoids, as well as theneurosteroids. All endogenous progestogens are characterized by their basic 21-carbon skeleton, called apregnane skeleton (C21). In similar manner, the estrogens possess anestrane skeleton (C18), and androgens, anandrostane skeleton (C19).
The termsprogesterone,progestogen, andprogestin are mistakenly used interchangeably both in the scientific literature and in clinical settings.[1][4][5]Progestins aresynthetic progestogens and are used in medicine.[2] Major examples of progestins include the17α-hydroxyprogesterone derivativemedroxyprogesterone acetate and the19-nortestosterone derivativenorethisterone. The progestins arestructural analogues of progesterone and have progestogenic activity similarly, but differ from progesterone in their pharmacological properties in various ways.[5]
In addition to their roles as natural hormones, progestogens are used asmedications, for instance inmenopausal hormone therapy andtransgender hormone therapy fortransgender women; for information on progestogens as medications, see theprogesterone (medication) andprogestogen (medication) articles.
The most important progestogen in the body isprogesterone (P4).[6][7] Otherendogenous progestogens, with varying degrees of progestogenic activity, include16α-hydroxyprogesterone (16α-OHP),[8]17α-hydroxyprogesterone (17α-OHP) (very weak),[9]20α-dihydroprogesterone (20α-DHP),[10][11]20β-dihydroprogesterone (20β-DHP),[11]5α-dihydroprogesterone (5α-DHP),[12]5β-dihydroprogesterone (5β-DHP) (very weak),[13][14]3β-dihydroprogesterone (3β-DHP),[15][16]11-deoxycorticosterone (DOC),[17] and5α-dihydrodeoxycorticosterone (5α-DHDOC).[18] They are allmetabolites of progesterone, lying downstream of progesterone in terms of biosynthesis.
The majortissues affected by progestogens include theuterus,vagina,cervix,breasts,testes, andbrain. The main biological role of progestogens in the body is in thefemale reproductive system, and themale reproductive system,[19] with involvement in regulation of themenstrual cycle, maintenance ofpregnancy, and preparation of themammary glands forlactation andbreastfeeding followingparturition in women; in men progesterone affectsspermiogenesis,sperm capacitation, andtestosterone synthesis. Progestogens also have effects in other parts of the body. Unlikeestrogens, progestogens have little or no role infeminization.[20]
Progesterone is produced fromcholesterol withpregnenolone as ametabolic intermediate. In the first step in thesteroidogenic pathway, cholesterol is converted into pregnenolone, which serves as theprecursor to the progestogens progesterone and 17α-hydroxyprogesterone. These progestogens, along with another steroid,17α-hydroxypregnenolone, are the precursors of all other endogenous steroids, including the androgens, estrogens, glucocorticoids, mineralocorticoids, and neurosteroids. Thus, many tissues producing steroids, including theadrenal glands,testes, andovaries, produce progestogens.
In some tissues, theenzymes required for the final product are not all located in a single cell. For example, inovarian follicles, cholesterol is converted toandrostenedione, an androgen, in thetheca cells, which is then further converted into estrogen in thegranulosa cells. Fetal adrenal glands also produce pregnenolone in some species, which is converted into progesterone and estrogens by the placenta (see below). In the human, the fetal adrenals producedehydroepiandrosterone (DHEA) via the pregnenolone pathway.
| Sex | Sex hormone | Reproductive phase | Blood production rate | Gonadal secretion rate | Metabolic clearance rate | Reference range (serum levels) | |
|---|---|---|---|---|---|---|---|
| Molar concentration | Mass concentration | ||||||
| Men | Androstenedione | – | 2.8 mg/day | 1.6 mg/day | 2200 L/day | 2.8–7.3 nmol/L | 80–210 ng/dL |
| Testosterone | – | 6.5 mg/day | 6.2 mg/day | 950 L/day | 6.9–34.7 nmol/L | 200–1000 ng/dL | |
| Estrone | – | 150 μg/day | 110 μg/day | 2050 L/day | 37–250 pmol/L | 10–70 pg/mL | |
| Estradiol | – | 60 μg/day | 50 μg/day | 1600 L/day | <37–210 pmol/L | 10–57 pg/mL | |
| Estrone sulfate | – | 80 μg/day | Insignificant | 167 L/day | 600–2500 pmol/L | 200–900 pg/mL | |
| Women | Androstenedione | – | 3.2 mg/day | 2.8 mg/day | 2000 L/day | 3.1–12.2 nmol/L | 89–350 ng/dL |
| Testosterone | – | 190 μg/day | 60 μg/day | 500 L/day | 0.7–2.8 nmol/L | 20–81 ng/dL | |
| Estrone | Follicular phase | 110 μg/day | 80 μg/day | 2200 L/day | 110–400 pmol/L | 30–110 pg/mL | |
| Luteal phase | 260 μg/day | 150 μg/day | 2200 L/day | 310–660 pmol/L | 80–180 pg/mL | ||
| Postmenopause | 40 μg/day | Insignificant | 1610 L/day | 22–230 pmol/L | 6–60 pg/mL | ||
| Estradiol | Follicular phase | 90 μg/day | 80 μg/day | 1200 L/day | <37–360 pmol/L | 10–98 pg/mL | |
| Luteal phase | 250 μg/day | 240 μg/day | 1200 L/day | 699–1250 pmol/L | 190–341 pg/mL | ||
| Postmenopause | 6 μg/day | Insignificant | 910 L/day | <37–140 pmol/L | 10–38 pg/mL | ||
| Estrone sulfate | Follicular phase | 100 μg/day | Insignificant | 146 L/day | 700–3600 pmol/L | 250–1300 pg/mL | |
| Luteal phase | 180 μg/day | Insignificant | 146 L/day | 1100–7300 pmol/L | 400–2600 pg/mL | ||
| Progesterone | Follicular phase | 2 mg/day | 1.7 mg/day | 2100 L/day | 0.3–3 nmol/L | 0.1–0.9 ng/mL | |
| Luteal phase | 25 mg/day | 24 mg/day | 2100 L/day | 19–45 nmol/L | 6–14 ng/mL | ||
Notes and sources Notes: "Theconcentration of a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. Thesecretion rate of a steroid refers to the total secretion of the compound from a gland per unit time. Secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. Themetabolic clearance rate of a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. Theproduction rate of a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. At steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). If there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate."Sources: See template. | |||||||
Progesterone is the major progestogen produced by thecorpus luteum of theovary in all mammalian species.Luteal cells possess the necessary enzymes to convert cholesterol to pregnenolone, which is subsequently converted into progesterone. Progesterone 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, theplacenta takes over the majority of progestogen production, whereas in other species the corpus luteum remains the primary source of progestogens. In the sheep and human, progesterone is the major placental progestogen.
The equine placenta produces a variety of progestogens, primarily5α-dihydroprogesterone and5α,20α-tetrahydroprogesterone, beginning on day 60. A complete luteo-placental shift occurs by day 120–150.
The endogenous progestogens arenaturally occurringpregnanesteroids withketone and/orhydroxyl groups at the C3 and C20 positions.
Progestogens, including bothprogesterone andprogestins, are used medically inhormonal birth control,hormone therapy, to treatgynecological disorders, to suppresssex hormone levels for various purposes, and for other indications.
In addition to progesterone, 20α- and 20β-hydroxyprogesterone (20α- and 20β-hydroxy-4-pregnene-3-one) also are found. These compounds have about one-fifth the progestational activity of progesterone in humans and other species.
In the Clauberg bioassay the 3β-hydroxy-4-pregnen-20-one shows about the same potency as progesterone (34). In regard to the biological activity of the 3α epimer no data are available.
{{cite journal}}: CS1 maint: multiple names: authors list (link) (the Women's Health, Osteoporosis, Progestin, Estrogen study)