Actions of Progestradiol Forte in details
Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, Estradiol (Progestradiol Forte) is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of Estradiol (Progestradiol Forte) daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.
Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.
Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Endogenous Progesterone (Progestradiol Forte) is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, Progesterone (Progestradiol Forte) transforms a proliferative endometrium into a secretory endometrium.
Progesterone (Progestradiol Forte) enhances cellular differentiation and generally opposes the actions of estrogens by decreasing estrogen receptor levels, increasing local metabolism of estrogens to less active metabolites, or inducing gene products that blunt cellular responses to estrogen. Progesterone (Progestradiol Forte) exerts its effects in target cells by binding to specific Progesterone (Progestradiol Forte) receptors that interact with Progesterone (Progestradiol Forte) response elements in target genes. Progesterone (Progestradiol Forte) receptors have been identified in the female reproductive tract, breast, pituitary, hypothalamus, and central nervous system.
How should I take Progestradiol Forte?
Take Progestradiol Forte only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.
Progestradiol Forte should come with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.
Take Progestradiol Forte with food.
Do not eat grapefruit or drink grapefruit juice while you are using Progestradiol Forte. Grapefruit and grapefruit juice may change the amount of Progestradiol Forte that is absorbed in the body.
Dosing
The dose of Progestradiol Forte will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Progestradiol Forte. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (capsules):
- For moderate to severe hot flashes:
- Adults—One capsule once a day, in the evening. Each capsule contains 1 milligram (mg) Estradiol (Progestradiol Forte) and 100 mg Progesterone (Progestradiol Forte).
- Children—Use is not recommended.
- For moderate to severe hot flashes:
Missed dose
If you miss a dose of Progestradiol Forte, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
If you miss a dose and it is more than 2 hours until your next dose, take the missed dose as soon as possible with food, then go back to your regular time.
If you miss a dose and it is within 2 hours of your next evening dose, skip the missed dose and go back to your regular dosing schedule.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Progestradiol Forte administration
Oral: Administer in the evening with food. In case of missed dose, administer with food as soon as possible, unless it is ≤2 hours until the next dose.
Progestradiol Forte pharmacology
Mechanism of Action
Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, Estradiol (Progestradiol Forte) is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of Estradiol (Progestradiol Forte) daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.
Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.
Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Endogenous Progesterone (Progestradiol Forte) is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, Progesterone (Progestradiol Forte) transforms a proliferative endometrium into a secretory endometrium.
Progesterone (Progestradiol Forte) enhances cellular differentiation and generally opposes the actions of estrogens by decreasing estrogen receptor levels, increasing local metabolism of estrogens to less active metabolites, or inducing gene products that blunt cellular responses to estrogen. Progesterone (Progestradiol Forte) exerts its effects in target cells by binding to specific Progesterone (Progestradiol Forte) receptors that interact with Progesterone (Progestradiol Forte) response elements in target genes. Progesterone (Progestradiol Forte) receptors have been identified in the female reproductive tract, breast, pituitary, hypothalamus, and central nervous system.
Pharmacodynamics
No specific pharmacodynamic studies were conducted with Progestradiol Forte (Progestradiol Forte) capsules, 1 mg/100 mg.
Pharmacokinetics
Absorption
The oral absorption of both Progestradiol Forte is subject to first pass metabolism. After multiple doses of Progestradiol Forte (Progestradiol Forte) capsules, 1 mg/100 mg, the tmax (the time at which the maximum concentration is attained) for Estradiol (Progestradiol Forte) is approximately 5 hours and approximately 3 hours for Progesterone (Progestradiol Forte) (Figure 1, Figure 2, and Table 2, below). Steady state for both Progestradiol Forte components of Progestradiol Forte, as well as Estradiol (Progestradiol Forte)'s main metabolite, estrone, is achieved within seven days.
Figure 1: Mean Steady-State Serum Estradiol (Progestradiol Forte) Concentrations Following Daily
Oral Administration of 1 mg Estradiol (Progestradiol Forte)/100 mg Progesterone (Progestradiol Forte) (Baseline Unadjusted, at Day 7)
Figure 2: Mean Steady-State Serum Progesterone (Progestradiol Forte) Concentrations Following Daily
Oral Administration of 1 mg Estradiol (Progestradiol Forte)/100 mg Progesterone (Progestradiol Forte) (Baseline Unadjusted, at Day 7)
| Dosage Strength (Progestradiol Forte) | Progestradiol Forte 1 mg/100 mg Mean (SD) | |
|---|---|---|
| *Effective t½. Calculated as 24•ln(2)/ ln(accumulation ratio/(accumulation ratio-1)) for subjects with accumulation ratio >1. | ||
| Abbreviations: AUC0-τ = area under the concentration vs time curve within the dosing interval at steady-state, Cavg = average concentration at steady-state, Cmax = maximum concentration, SD = standard deviation, tmax = time to maximum concentration, t½ = half-life | ||
| Estradiol (Progestradiol Forte) | N | |
| AUC0-τ (pg·h/mL) | 20 | 772.4 (384.1) |
| Cmax (pg/mL) | 20 | 42.27 (18.60) |
| Cavg (pg/mL) | 19 | 33.99 (14.53) |
| tmax (h) | 19 | 4.93(4.97) |
| t½ (h)* | 19 | 26.47 (14.61) |
| Estrone | ||
| AUC0-τ (pg·h/mL) | 20 | 4594 (2138) |
| Cmax (pg/mL) | 20 | 238.5 (100.4) |
| Cavg (pg/mL) | 20 | 192.1 (89.43) |
| tmax (h) | 20 | 5.45 (3.47) |
| t½ (h)* | 19 | 22.37 (7.64) |
| Progesterone (Progestradiol Forte) | ||
| AUC0-τ (ng·h/mL) | 20 | 18.05 (15.58) |
| Cmax (ng/mL) | 20 | 11.31 (23.10) |
| Cavg (ng/mL) | 20 | 0.76 (0.65) |
| tmax (h) | 20 | 2.64 (1.51) |
| t½ (h) | 18 | 9.98 (2.57) |
Food Effect
Concomitant food ingestion increased the AUC and Cmax of the Progesterone (Progestradiol Forte) component of Progestradiol Forte relative to a fasting state when administered at a dose of 100 mg. In a study where Progestradiol Forte was administered to postmenopausal women at a dose of 1 mg Estradiol (Progestradiol Forte)/100 mg Progesterone (Progestradiol Forte) within 30 minutes of starting a high-fat meal, the Cmax and AUC of Progesterone (Progestradiol Forte) were 162% and 79% higher, respectively, relative to the fasting state. Concomitant food ingestion had no effect on the AUC of the Estradiol (Progestradiol Forte) component of Progestradiol Forte but decreased Cmax by approximately 54% and delayed Tmax to 12 hours.
Distribution
Estradiol (Progestradiol Forte)
The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulating in the blood largely are bound to SHBG and albumin.
Progesterone (Progestradiol Forte)
Progesterone (Progestradiol Forte) is approximately 96% to 99% bound to serum proteins, primarily to serum albumin (50% to 54%) and transcortin (43% to 48%).
Elimination
Following repeat dosing with Progestradiol Forte (Progestradiol Forte) capsules, 1 mg/100 mg, the half-life of Estradiol (Progestradiol Forte) was approximately 26 hours. The half-life of Progesterone (Progestradiol Forte), following repeat dosing was approximately 10 hours.
Metabolism
Estradiol (Progestradiol Forte)
Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol (Progestradiol Forte) is converted reversibly to estrone, and both can be converted to estriol, the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.
Progesterone (Progestradiol Forte)
Progesterone (Progestradiol Forte) is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone (Progestradiol Forte) metabolites, which are excreted in the bile, may be deconjugated and may be further metabolized in the intestine via reduction, dehydroxylation, and epimerization.
Excretion
Estradiol (Progestradiol Forte)
Estradiol (Progestradiol Forte), estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.
Progesterone (Progestradiol Forte)
The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the bile and urine. Progesterone (Progestradiol Forte) metabolites are eliminated mainly by the kidneys. Progesterone (Progestradiol Forte) metabolites which are excreted in the bile may undergo enterohepatic recycling or may be excreted in the feces.
References
- DailyMed. "PROGESTERONE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DailyMed. "ESTRADIOL HEMIHYDRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Therapeutic Progesterone: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Progestradiol Forte are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Progestradiol Forte. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
