| Candidate ID: | R0109 |
| Source ID: | DB00396 |
| Source Type: | approved; vet_approved |
| Compound Type: |
small molecule
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| Compound Name: |
Progesterone
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| Synonyms: |
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| Molecular Formula: |
C21H30O2
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| SMILES: |
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
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| Structure: |
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| DrugBank Description: |
Progesterone is a hormone that occurs naturally in females, and is essential for endometrial receptivity, embryo implantation, and the successful establishment of pregnancy. A low progesterone concentration or an insufficient response to progesterone can cause infertility and pregnancy loss [A175609]. Progesterone is used in various contraceptive preparations to prevent ovulation and fertilization [T481], [A175612] as well as in other formulations to promote and support pregnancy. Please see [Medroxyprogesterone acetate], [Megestrol acetate], [Dydrogesterone] and [Hydroxyprogesterone] entries for information on various other forms of progesterone.
Pharmaceutical progesterone is made from a plant source as a starting material and is chemically identical to progesterone of human ovarian origin [FDA label]. Progesterone is available in gelatinized capsule form, vaginal gel form, tablet form, vaginal insert form, and injection form, all used for various purposes [Label,F3898,F3904,F3901,F3907].
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| CAS Number: |
57-83-0
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| Molecular Weight: |
314.4617
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| DrugBank Indication: |
**Gelatinized capsules**
The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea [FDA label].
**Vaginal gel**
Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel [F3898].
**Vaginal insert**
This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women [F3901].
**Injection (intramuscular)**
This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer [F3907].
**Tablets, contraceptive**
The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy [F3904].
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| DrugBank Pharmacology: |
Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below:
General effects
Progesterone is the main hormone of the corpus luteum and the placenta. It acts on the uterus by changing the proliferative phase to the secretory phase of the endometrium (inner mucous lining of the uterus). This hormone, stimulated by a hormone called _luteinizing hormone_ (LH) is the main hormone during the secretory phase to prepare the corpus luteum and the endometrium for implantation of a fertilized ovum. As the luteal phase concludes, the progesterone hormone sends negative feedback to the anterior pituitary gland in the brain to decrease FSH (follicle stimulating hormone) and LH (luteinizing hormone) levels. This prevents ovulation and maturation of oocytes (immature egg cells). The endometrium then prepares for pregnancy by increasing its vascularity (blood vessels) and stimulating mucous secretion. This process occurs by progesterone stimulating the endometrium to decrease endometrial proliferation, leading to a decreased uterine lining thickness, developing more complex uterine glands, collecting energy in the form of glycogen, and providing more uterine blood vessel surface area suitable for supporting a growing embryo. As opposed to cervical mucous changes observed during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucus, rendering it less elastic. This change occurs because the fertilization time period has passed, and a specific consistency of mucous amenable to sperm entry is no longer required [T490].
**Gelatinized capsules**
Progesterone capsules are an oral dosage form of micronized progesterone which, chemically identical to progesterone of ovarian origin. Progesterone capsules have all the properties of endogenous progesterone with induction of a secretory phase endometrium with gestagenic, antiestrogenic, slightly antiandrogenic and anti-aldosterone effects [F3913]. Progesterone opposes the effects of estrogen on the uterus, and is beneficial in women with unopposed estrogen exposure, which carries an increased risk of malignancy [F3913].
**Vaginal gel and vaginal insert**
The gel preparation mimics the effects of naturally occurring progesterone. In the presence of adequate levels of estrogen, progesterone converts a proliferative endometrium into secretory endometrium. This means that the endometrium changes from a growing and thickening stage into a subsequent preparation stage for pregnancy, which involves further preparatory changes. Progesterone is necessary for the development of decidual tissue (specialized tissue amenable to supporting a possible pregnancy). Progesterone is required to increase endometrial receptivity for the implantation of a fertilized embryo. Once an embryo is implanted, progesterone helps to maintain the pregnancy [F3898].
**Injection (intramuscular)**
Intramuscularly injected progesterone increases serum progesterone and aids in the prevention of endometrial tissue overgrowth due to unopposed estrogen (which leads to abnormal uterine bleeding and sometimes uterine cancer) [L5638], [F3916]. In the absence or deficiency of progesterone, the endometrium continually proliferates, eventually outgrowing its limited blood supply, shedding incompletely, and leading to abnormal and/or profuse bleeding as well as malignancy [L5638].
**Tablets, contraceptive**
Progesterone-only contraceptive tablets prevent conception by suppressing ovulation in about half of users, causing a thickening of cervical mucus to inhibit sperm movement, lowering the midcycle LH and FSH hormone peaks, slowing the movement of the ovum through the fallopian tubes, and causing secretory changes in the endometrium as described above [F3904].
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| DrugBank MoA: |
Progesterone binds and activates its nuclear receptor, _PR_, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy.
Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues [A175666]. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy [A175651].
Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills [F3904].
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| Targets: |
Progesterone receptor; Mineralocorticoid receptor; Estrogen receptor alpha; Steroid 17-alpha-hydroxylase/17,20 lyase; Kappa-type opioid receptor; Alpha-1-acid glycoprotein 1; Glucocorticoid receptor; Androgen receptor; Sex hormone-binding globulin; Estrogen receptor beta
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| Inclusion Criteria: |
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