Progestogens are a group of hormone

Hormone

A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s including progesterone

Progesterone

Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

.
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.

Progestogens as precursors to other steroids

In the first step in the steroidogenic pathway, a cholesterol

Cholesterol

Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 molecule is converted into pregnenolone

Pregnenolone

Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...

 (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

Corpus luteum

The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...

 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

Estrous cycle

The estrous cycle comprises the recurring physiologic changes that are induced by reproductive hormones in most mammalian placental females. Estrous cycles start after puberty in sexually mature females and are interrupted by anestrous phases or pregnancies...

.

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.

Birth control

• Progestogens are used alone in progestogen-only pills, or with an estrogen
  Estrogen
  Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
  
   in combined oral contraceptive pills, a contraceptive patch
  Contraceptive patch
  A contraceptive patch is a transdermal patch applied to the skin that releases synthetic estrogen and progestin hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.The...
  
  , and a contraceptive vaginal ring
  NuvaRing
  NuvaRing is the trade name for a combined hormonal contraceptive vaginal ring manufactured by Merck that is available by prescription...
  
  .
• Medroxyprogesterone acetate (Depo-Provera) and norethindrone enantate (Noristerat) are used by depot injection.
• Etonogestrol is released by subcutaneous implants (Implanon
  Implanon
  Implanon, made by Organon International, is a single-rod long acting reversible hormonal contraceptive subdermal implant that is inserted just under the skin of a woman's upper arm. The 4 cm by 2 mm Implanon rod contains 68 milligrams of etonogestrel which is released over a three year...
  
  ). Norplant
  Norplant
  Norplant is a form of birth control developed by the Population Council that was first approved in 1983 in Finland, where it was manufactured by Leiras Oy Pharmaceuticals...
  
   and Jadelle implants release levonorgestrel
  Levonorgestrel
  Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
  
  .
• Levonorgestrel is released by the intrauterine system
  IntraUterine System
  The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called levonorgestrel...
  
   IUS (Mirena).

Antiandrogen

Progestinic compounds decrease luteinizing hormone

Luteinizing hormone

Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (LH) levels and, as such, will have antiandrogen

Antiandrogen

Antiandrogens, or androgen antagonists, first discovered in the 1960s, prevent androgens from expressing their biological effects on responsive tissues. Antiandrogens alter the androgen pathway by blocking the appropriate receptors, competing for binding sites on the cell's surface, or affecting...

ic properties in trans-women and male

Male

Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...

s alike, due to decreased LH stimulation of the testes

Testicle

The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...

. Cyproterone

Cyproterone

Cyproterone acetate is an antiandrogen...

 is a common example of a progestinic medication, and is an effective antiandrogen

Antiandrogen

Antiandrogens, or androgen antagonists, first discovered in the 1960s, prevent androgens from expressing their biological effects on responsive tissues. Antiandrogens alter the androgen pathway by blocking the appropriate receptors, competing for binding sites on the cell's surface, or affecting...

, which has the added benefit of blocking androgen receptors

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 in addition to the progestinic feedback to decrease LH levels.

Progestogen withdrawal bleeding

In a normal menstrual cycle

Menstrual cycle

The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....

, declining levels of progesterone triggers menstruation. Norethindrone acetate

Norethindrone acetate

Norethisterone acetate or norethindrone acetate is a progestin used in contraception. It is the acetate ester of norethisterone....

 (brand name Aygestin) and medroxyprogesterone acetate (brand name Provera) may be used to artificially induce progestogen withdrawal bleeding.

Cachexia Syndrome

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

Dexamethasone

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

. 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

Adverse effects of progestogens include weak androgenic actions, acne, fluid retention

Water retention (medicine)

The term water retention signifies an abnormal accumulation of fluid in the circulatory system or within the tissues or cavities of the body.Water is found both inside and outside the body’s cells...

, weight changes, depression, change in libido

Libido

Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, breast discomfort, premenstrual syndrome, irregular menstrual cycles, and breakthrough bleeding

Breakthrough bleeding

Breakthrough bleeding is an abnormal uterine bleeding that occurs between menstrual periods, especially due to irregular sloughing of the endometrium in women on combined oral contraceptives...

. Also, there is an increased risk of thromboembolism.

External links

• The Nomenclature of Steroids
• The Million Women Study (the Women's Health, Osteoporosis, Progestin, Estrogen study)