Progesterone (Pic.1) is an endogenous steroid and progestogen sex hormone. Progestogens are a class of steroid hormones that bind to and activate the progesterone receptor. The most important progestogen in the body is progesterone (P4). Other endogenous progestogens include progesteron, progestogen, a progestin. The progestogens are named for their function in maintaining pregnancy (i.e., progestational), although they are also present at other phases of the estrous and menstrual cycles. Progesterone is the major progestogen in the body, and plays an important role in brain function as a neurosteroid. In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. Progesterone levels are relatively low in children and postmenopausal women. Adult males have levels similar to those in women during the follicular phase of the menstrual cycle (Pic. 2).

Reproductive system:

Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified. Detailed characterization of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes, slow calcium oscillations, now thought to possibly regulate motility.

Progesterone is sometimes called the "hormone of pregnancy", and it has many roles:

  • Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation (Pic. 3). At the same time progesterone affects the vaginal epithelium and cervical mucus, making it thick and impenetrable to sperm. Progesterone is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation (Pic. 4).
  • Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to anovulatory dysfunctional uterine bleeding.
  • During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy.
  • Progesterone decreases contractility of the uterine smooth muscle.
  • In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
  • A drop in progesterone levels is possibly one step that facilitates the onset of labor.

Prevention of preterm birth:

Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy. A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care. In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.


Progesterone plays an important role in mammary gland development in females. In conjunction with prolactin, it mediates lobuloalveolar maturation of the breasts during pregnancy to allow for milk production, and thus lactation and breastfeeding after childbirth.

Progesterone is also part of hormonal contraceptives:

  • the two main types of hormonal contraception either contain only progesterone or a combination of estrogen and progesterone
  • hormonal contraceptives that contain estrogen and progesterone prevent pregnancy by inhibiting ovulation
  • combined contraceptives suppress ovulation by inhibiting gonadotropin secretion
  • progesterone-only contraceptives inhibit pregnancy mostly by secondary mechanisms such as thickening of cervical mucus and endometrial changes

Other effects of progesterone:

  • increases core temperature (thermogenic function) during ovulation
  • reduces spasm and relaxes smooth muscle, bronchi are widened and mucus regulated (PRs are widely present in submucosal tissue)
  • acts as an anti-inflammatory agent and regulates the immune response
  • reduces gall-bladder activity
  • normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy
  • may affect gum health, increasing risk of gingivitis (gum inflammation)
  • appears to prevent endometrial cancer (involving the uterine lining) by regulating the effects of estrogen
  • plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes
  • may play a role in male behavior, such as in male aggression towards infants


Since most progesterone in males is created during testicular production of testosterone, and most in females by the ovaries, the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of progestogens in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.

The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.


Progesterone enhances the function of serotonin receptors in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance serotonin activity such as nicotine, alcohol, and cannabis when their progesterone levels fall below optimal levels.
To examine the effects of progesterone on nicotine addiction, participants in one study were either treated orally with a progesterone treatment, or treated with a placebo. When treated with progesterone, participants exhibited enhanced suppression of smoking urges, reported higher ratings of “bad effects” from IV nicotine, and reported lower ratings of “drug liking”.These results suggest that progesterone not only alters the subjective effects of nicotine, but reduces the urge to smoke cigarettes.

Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels. Therefore, females have an increased biological vulnerability to nicotine’s reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior.

Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.

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