What it's for (Indications)
- Used as a hormonal supplement.
- In postmenopausal women with an intact uterus who are receiving estrogen therapy, it is used to prevent abnormal thickening of the uterine lining (endometrial hyperplasia), reduce the risk of uterine cancer, and as part of hormone replacement therapy.
- For women of child-bearing age, it is used to regulate the menstrual cycle in cases of secondary amenorrhea.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For the prevention of endometrial hyperplasia in postmenopausal women with an intact uterus who are receiving daily conjugated estrogens tablets, administer 200 mg orally once daily at bedtime for 12 days sequentially per 28-day cycle. For the treatment of secondary amenorrhea, administer 400 mg orally once daily at bedtime for 10 days. Capsules should be taken with a glass of water while in a standing position if difficulty swallowing is experienced. Do not exceed the recommended daily dose. Do not use for longer than prescribed. Do not alter dosage without a doctor’s approval. Store at 20-25°C (68-77°F) [USP Controlled Room Temperature]. Protect from excessive moisture. Dispense in a tight, light-resistant container. Keep out of reach of children. |
Safety & Warnings
Common Side Effects
- Commonly reported side effects include breast tenderness, headache, heavy non-menstrual vaginal bleeding, pain in the pelvis, white or brown vaginal discharge, tiredness, vomiting, diarrhea, constipation, mood swings, irritability, and muscle, joint, or bone pain.
Serious Warnings
- Black Box Warning: WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA FOR ESTROGEN PLUS PROGESTIN THERAPY. Estrogens plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women (50 to 79 years of age).
- Caution is advised for pregnant women; this medicine may be used, but consult your healthcare provider.
- It is not recommended for use by lactating females; consult your healthcare provider.
- This medicine may cause dizziness or drowsiness; do not drive a vehicle immediately after taking it.
- Use with extreme caution in patients with known liver disease or kidney disease.
- Reduce alcohol consumption while taking this medication.
- Do not exceed the recommended daily dose.
- Do not use for longer than it is prescribed.
- Do not alter your dosage without a doctor’s approval.
- Avoid grapefruit and grapefruit juice.
- Provide your doctor with a complete medical history, especially of kidney disease, liver disease, unexplained vaginal bleeding, miscarriage, breast or reproductive organ cancer, diabetes, depression, blood clots (thrombosis), migraine, seizures, and gallbladder disease.
- Inform your doctor about all prescription, non-prescription, and herbal medications you are taking or plan to take.
- Inform your doctor that you are taking progesterone before undergoing any kind of surgery.
- Get out of bed slowly and rest your feet on the floor for a few minutes before standing up to mitigate dizziness.
- Consult your doctor if your condition persists or worsens.
- Do not give progesterone to children unless advised by a medical professional.
- If experiencing difficulty swallowing, take capsules with a glass of water while in a standing position.
How it Works (Mechanism of Action)
Progesterone is a naturally occurring steroid hormone primarily synthesized from cholesterol in the corpus luteum, adrenal cortex, and placenta during pregnancy. Its physiological effects are mediated through specific intracellular progesterone receptors (PRs), which are members of the nuclear receptor superfamily of ligand-activated transcription factors. These receptors exist in two main isoforms, PR-A and PR-B, which are differentially expressed across target tissues and possess distinct transcriptional activities. Progesterone receptors are widely distributed in reproductive tissues, including the uterus, ovaries, mammary glands, and also in the central nervous system, cardiovascular system, and immune cells.
Upon binding of progesterone, the hormone-receptor complex undergoes a conformational change, disassociates from associated chaperone proteins (e.g., heat shock proteins), dimerizes, and translocates from the cytoplasm into the cell nucleus. Within the nucleus, the activated progesterone-receptor complex directly binds to specific DNA sequences known as progesterone response elements (PREs) located in the promoter regions of target genes. This binding event modulates gene transcription, leading to either activation or repression of gene expression, thereby regulating a wide array of cellular processes, including proliferation, differentiation, and secretory activity. Progesterone also exhibits rapid, non-genomic effects that are mediated by membrane-bound progesterone receptors or other signaling pathways, although the genomic mechanism is considered the primary mode of action for its therapeutic and physiological roles.
In the female reproductive system, progesterone plays a critical role in preparing the endometrium for embryo implantation by inducing secretory changes in the estrogen-primed uterine lining. It also reduces uterine smooth muscle contractility and excitability, which is essential for maintaining a quiescent uterus during pregnancy and preventing premature contractions. Furthermore, progesterone influences cervical mucus characteristics, making it thicker and less permeable to sperm, and supports the development of mammary glands during pregnancy. Its immunomodulatory properties are also crucial in pregnancy, helping to prevent maternal immune rejection of the semi-allogeneic fetus. The overall effect of progesterone in target tissues is highly dependent on prior or concurrent exposure to estrogen, which typically upregulates progesterone receptor expression, thus enhancing the tissue's sensitivity to progesterone.