| Indication |
For progesterone supplementation or replacement as part of an
Assisted Reproductive Technology (ART) treatment for infertile women
with progesterone deficiency and for the treatment of secondary
amenorrhea. Also used for the reduction of the incidence of endometrial
hyperplasia and the attendant risk of endometrial carcinoma in
postmenopausal women receiving estrogen replacement therapy, as well as
treatment of abnormal uterine bleeding due to hormonal imbalance in the
absence of organic pathology such as fibroids or uterine cancer. |
| Pharmacodynamics |
Progesterone is a naturally occuring progestin or a synthetic
form of the naturally occurring female sex hormone, progesterone. In a
woman's normal menstrual cycle, an egg matures and is released from the
ovaries (ovulation). The ovary then produces progesterone, preventing
the release of further eggs and priming the lining of the womb for a
possible pregnancy. If pregnancy occurs, progesterone levels in the body
remain high, maintaining the womb lining. If pregnancy does not occur,
progesterone levels in the body fall, resulting in a menstrual period.
Progesterone tricks the body processes into thinking that ovulation has
already occurred by maintaining high levels of the synthetic
progesterone. This prevents the release of eggs from the ovaries. |
| Mechanism of action |
Progesterone shares the pharmacological actions of the progestins.
Progesterone binds to the progesterone and estrogen receptors. Target
cells include the female reproductive tract, the mammary gland, the
hypothalamus, and the pituitary. Once bound to the receptor, progestins
like Progesterone will slow the frequency of release of gonadotropin
releasing hormone (GnRH) from the hypothalamus and blunt the
pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate
endogenous estrogen, progesterone transforms a proliferative
endometrium into a secretory one. Progesterone is essential for the
development of decidual tissue and is necessary to increase endometrial
receptivity for implantation of an embryo. Once an embryo has been
implanted, progesterone acts to maintain the pregnancy. Progesterone
also stimulates the growth of mammary alveolar tissue and relaxes
uterine smooth muscle. It has little estrogenic and androgenic activity. |
| Absorption |
Progesterone absorption is prolonged with an absorption half-life of approximately 25-50 hours. |
| Volume of distribution |
Not Available |
| Protein binding |
96%-99% |
| Metabolism |
Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. |
| Route of elimination |
The glucuronide and sulfate conjugates of pregnanediol and
pregnanolone are excreted in the urine and bile. Progesterone
metabolites which are excreted in the bile may undergo enterohepatic
recycling or may be excreted in the feces. Progesterone metabolites are
excreted mainly by the kidneys. |
| Half life |
34.8-55.13 hours |
| Clearance |
- 2510 +/- 135 L/day [cycling women]
|
| Toxicity |
Not Available |
