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Divina® [Medroxyprogesterone, Estradiol]

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Clinical Pharmacology

DIVINA - combined hormonal drug


Estradiol valerate is an ether of natural estrogen - estradiol. The pharmacological effects of estradiol are carried out through specific estrogen receptors in target tissues. By binding to specific receptors, estrogens, among other effects, stimulate endometrial growth and contribute to the development of secondary sexual characteristics.
Medroxyprogesterone acetate is a derivative of natural progesterone -17-alpha-hydroxy-6-methylprogesterone. Medroxyprogesterone acetate binds to progestin-specific receptors and acts on the endometrium, transferring it from the proliferative to the secretory phase.
Estradiol stimulates endometrial growth while increasing the risk of endometrial hyperplasia and cancer. Medroxyprogesterone acetate is added to treatment to counteract this effect.


After ingestion of estradiol, valerate is absorbed from the gastrointestinal tract (GIT) and undergoes hydrolysis to estradiol using esterases in the liver and the wall of the small intestine. The maximum concentration of estradiol in plasma is reached after 4-6 hours. Circulating estradiol binds to plasma proteins, mainly with sex hormone-binding globulin, and serum albumin.
Metabolites are excreted in the urine in the form of glucuronide and sulphate conjugates. A small portion of the dose is excreted in the feces.
After ingestion of one tablet of the drug Divisek, the maximum concentration of medroxyprogesterone acetate in the blood plasma is reached within 1-2 hours.
Medroxyprogesterone acetate binds to plasma proteins by more than 90% (mainly albumin). In oral administration, the half-life of medroxyprogesterone acetate is 24-48 hours. Medroxyprogesterone acetate is extensively metabolized in the liver by hydroxylation and conjugation.
Medroxyprogesterone acetate is excreted in the urine and bile.


Hormone replacement therapy (HRT) for the symptoms of estrogen deficiency and progesterone.


1 white tablet with:

Active substance: estradiol valerat2 mg;

Excipients: lactose monohydrate; corn starch; gelatin; magnesium stearate; talc; Kollidon K25; indigo carmine (E132), purified water.

1 blue tablet contains:

Active substances:estradiol valerat2 mg; medroxyprogesterone acetate 10 mg;

Excipients: lactose monohydrate; corn starch; gelatin; magnesium stearate; talc; Kollidon K25; indigo carmine (E132), purified water.

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Divina® [Medroxyprogesterone, Estradiol]

Dosage and Administration

Inside 1 tablet per day (preferably in the evening) for 21 days, followed by a 7-day break, during which menstrual-like bleeding occurs, after which they start again.

For the first 11 days, take white pills containing only estrogen, then for 10 days - blue pills containing a combination of estrogen with progesterone. The drug can be started at any time, if the normal menstrual cycle has stopped or if it is irregular, as well as on the 5th day after the start of menstruation.

Menstrual-like bleeding begins within a week, free from taking Divina. In menopause, there may be differences in the duration of the menstrual cycle. Bleeding can begin while taking blue pills (in this case, the admission should be immediately stopped, and after stopping the bleeding, white pills can be resumed).

If you miss the pill, it should be taken no later than 12 hours and then take the drug in the usual way.

Adverse reactions

The nervous system: headache; mood changes, including anxious and depressed mood; dizziness; migraine; sleep disorders

From the digestive system: nausea, abdominal pain, dyspepsia, vomiting, flatulence, cholecystitis, cholelithiasis, diarrhea or constipation.

Since the cardiovascular system: increased blood pressure, rarely - thrombosis, palpitations.

From the endocrine system: alopecia, hirsutism, engorgement of the mammary glands, an increase in myomatous nodes.

Allergic reactions: rash, pruritus, erythema multiforme exudative, nodular erythema.

Other: uterine bleeding, vaginal candidiasis, fluctuations in body weight, peripheral edema, changes in libido, cramps in the muscles of the lower extremities, visual disturbances, increased liver plasma transaminase activity (ALT and ACT), alkaline phosphatase, gamma glutamyltransferase, lupus syndrome.

Carefully: MS , estrogen-dependent tumors in history, cholelithiasis, marked obesity (including history), migraine, herpes infection in a Amnesia.

Drug interactions

The estrogenic effect of Divina can be reduced while taking it with antihypertensive drugs, indirect anticoagulants, oral hypoglycemic agents; baobiturata, hydantoin, rifampicin, ampicillin, tetracycline, as well as with preparations of microsomal oxidation inducers (including phenytoin, antiepileptic drugs, griseofulvin).
The estrogenic effect of Divina can increase while taking it with drugs that inhibit microsomal oxidation (ketoconazole, cyclosporine).

Pregnancy and Lactation

Divina is contraindicated during pregnancy and lactation.

Special instructions

The drug Divina is not a contraceptive and does not protect against pregnancy. Taking Divin may reduce the effectiveness of high-pressure drugs and antidiabetic drugs. The effectiveness of the drug reduce rifampicin, carbamazepine

Studies and clinical trials of Medroxyprogesterone, Estradiol (Click to expand)
  1. Anxiolytic and Antidepressant Effects of Divaza and Brizantin
  2. Study of 17β-estradiol-3-benzoate, 17α-methyltestosterone and medroxyprogesterone acetate fixation in bovine hair
  3. Development and validation of a reversed-phase liquid chromatographic method for analysis of estradiol valerate and medroxyprogesterone acetate in a tablet formulation
  4. Elevated Concentrations of Ethinylestradiol, 17β-Estradiol, and Medroxyprogesterone have Little Effect on Reproduction and Survival ofCeriodaphniadubia
  5. Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys
  6. Phasic serum lipid excursions during cyclic oral conjugated estrogens (OCE) but not during transdermal estradiol (TE) sequentially combined with oral medroxyprogesterone acetate (MPA)
  7. Combined effects of estradiol, leuprorelin, tamoxifen and medroxyprogesterone acetate on cell growth and steroid hormone receptors in breast cancer cells
  8. Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women
  9. Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17β-estradiol and norethindrone acetate
  10. Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy
  11. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures
  12. Vascular Endothelial Growth Factor Expression Is Not Regulated by Estradiol or Medroxyprogesterone Acetate in Endometrial Carcinoma
  13. Plasma levels of medroxyprogesterone acetate (MPA), estradiol and progesterone in the rhesus monkey after intramuscular administration of depo-provera®
  14. Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium
  15. Menstrual pattern and lipid profiles during use of medroxyprogesterone acetate and estradiol cypionate and NET-EN (200 mg) as contraceptive injections
  16. Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)
  17. Effects of Estradiol and Medroxyprogesterone Acetate on Vascular Function in Young Women
  18. Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women
  19. Pharmacokinetics of estradiol valerate and medroxyprogesterone acetate in different age groups of postmenopausal women
  20. Estradiol and medroxyprogesterone acetate regulated genes in T47D breast cancer cells
  21. Medroxyprogesterone acetate attenuates long-term effects of 17β-estradiol in coronary arteries from hyperlipidemic rabbits
  22. Synchronization of follicular wave emergence in the seasonally anestrous ewe: The effects of estradiol with or without medroxyprogesterone acetate
  23. Effects of long-term treatment with 17 β-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats

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