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Dydrogesterone ball-and-stick.png
Systematic (IUPAC) name
Clinical data
AHFS/Drugs.com International Drug Names
Pharmacokinetic data
Bioavailability 28%
Metabolism complete, 20-dihydrodydrogesterone (DHD) metabolite
Half-life dydrogesterone (5-7 hours) & DHD (14-17 hours)
152-62-5 YesY
PubChem CID 9051
DrugBank DB00378 YesY
ChemSpider 8699 YesY
Chemical data
Formula C21H28O2
312.446 g/mol
Physical data
Melting point 144 °C (291 °F)
Boiling point 463 °C (865 °F)
insoluble mg/mL (20 °C)
 N (what is this?)  (verify)

Dydrogesterone (INN, USAN, BAN), is also chemically known as 9β,10α-pregna-4,6-diene-3,20-dione.[1] It is a steroidal progestin first introduced to the market in 1961. It has been approved in more than 100 countries worldwide with a total exposure in over 28 million pregnancies.[2] It is commercially marketed under the brand name Duphaston and manufactured by Abbott (formerly known as Solvay Pharmaceuticals).[3]

Dydrogesterone is used as an effective, orally active progestogen for gynaecological conditions related to a wide variety of progesterone deficiencies in pregnant women.[4] The molecular structure and pharmacological effects are somewhat similar to endogenous progesterone, although in smaller amounts it is found to be orally active. Its freedom from hormonal effects like those related to corticoid, androgenic, estrogenic, anabolic, and other effects gives Dydrogesterone an advantage over other synthesized progestogens.[3]

Dydrogesterone when used therapeutically is closely related to its physiological action on the neuro-endocrine control of ovarian function, as well as on the endometrium. This is an indication in all cases of endogeneous progesterone deficiency - relative or absolute. As of March 2008, Dydrogesterone is to be withdrawn from the UK market due to commercial reasons as cited by the company. The molecule was licensed for use in several indications, including the threat of or recurrent miscarriage, dysfunctional bleeding in the uterus and also as a hormone replacement therapy.[2]

Dydrogesterone has proven effective in the following conditions associated with progesterone deficiency:[5]

Dydrogesterone has also been registered as hormone replacement therapy (HRT)[10] to countercheck the negative effects of unopposed estrogen on the endometrium in women with an intact uterus. Dydrogesterone is relatively safe and well tolerated, and does not exhibit the androgenic side effects that are common with some other progestins, like medroxyprogesterone acetate.[11]


Menstrual disorders[edit]


Primary or essential dysmenorrhea is a very common gynaecological phenomenon experienced by women during their reproductive years. Clinical studies have shown symptom relief and a reduction in pain with dydrogesterone treatment for dysmenorrhea.[12]

Secondary amenorrhoea[edit]

Secondary amenorrhoea is not a specific disease, but is instead a symptom. Dydrogesterone has been found to adequately induce bleeding within a sufficiently estrogen-primed endometrium. When estradiol levels are found to be low, dydrogesterone treatment is more effective when supplemented with estrogens.[13]

Dysfunctional uterine bleeding and irregular cycles[edit]

Apart from a wide variety of medications in use to reduce heavy menstrual bleeding in patients with ovulatory cycles, oral progestogens like dydrogesterone have been found to be the most commonly prescribed as it has been found to prevent heavy bleeding.[14]

Infertility, recurrent pregnancy loss and preterm birth[edit]

Dydrogesterone is used for luteal support in IVF protocols, for treatment of recurrent pregnancy loss, and for prevention of preterm birth in pregnant women with a history of at least one spontaneous preterm birth.[15]


Endometriosis is a chronic disease which can cause severe, progressive, and at times, incapacitating dysmenorrhoea, pelvic pain, dyspareunia and infertility. Dydrogesterone relieves pain without inhibiting ovulation, so that patients are able to become pregnant during treatment. The efficacy of dydrogesterone on the lesions of endometriosis is less clear, but their number and severity does not seem to correlate with the severity of symptoms.[16]

Premenstrual syndrome[edit]

Dydrogesterone has shown reasonable efficacy in relieving a number of premenstrual syndrome symptoms like mood swings & physical symptoms.[8]

Hormone replacement therapy[edit]

The objective behind hormone replacement therapy is to actively increase the circulating levels of estrogen to control hot flushes and to prevent the long-term effects of the menopause, such as bone resorption and unfavourable changes in blood lipids. The administration of 17β-oestradiol halts, or reverses atrophic changes that occur due to the loss of endogenous oestradiol during the menopause.[17]

Estrogen promotes endometrial cell growth and in postmenopausal women with an intact uterus, estrogen monotherapy results in continued endometrial development without the physiological secretory changes normally brought on by progesterone. This action is associated with an increased incidence of endometrial hyperplasia and carcinoma. Additional protection with progestogens is therefore important in patients with an intact uterus who receive estrogen replacement therapy. Dydrogesterone counters the proliferative effect of estrogens on the endometrium and ensures the transition to a secretory pattern and cyclical shedding of the endometrium in serial HRT regimes. Dydrogesterone effectively protects against the ontogenesis of endometrial hyperplasia. Unlike androgenic progestogens, dydrogesterone does not reverse the benefits brought on by 17β-oestradiol on lipid profiles and carbohydrate metabolism. In a continuous, combined HRT regimen, dydrogesterone retards the proliferation of the endometrium so that it remains atrophic or inactive.[18]


Dydrogesterone was first synthesised by Duphar in the 1950s. Although its molecular structure is almost identical to that of natural progesterone, its unique design makes it a potent, orally active progestogen.[19] In the dydrogesterone molecule, the hydrogen atom at carbon 9 is in the beta position and the methyl group at carbon 10 is in the alpha position - a reverse of the progesterone structure, hence the term 'retro' progesterone. Furthermore, it has a second double bond between carbon 6 and carbon 7 (the 4, 6-diene-3-one configuration). These small differences in chemical structure account for the improved oral activity, metabolic stability, and the lack of estrogenic, androgenic glucocorticoid, and mineralocorticoid properties of dydrogesterone.[20]



Dydrogesterone is readily absorbed after oral administration. Tmax values vary between 0.5 and 2.5 hours.[21] Dydrogesterone is virtually completely metabolised. The primary reaction (metabolic) is the hydrogenation of the 20-keto group, leading to 20-dihydrodydrogesterone (DHD), which is another powerful progestogen. The levels of DHD, which is the main active metabolite, is also found to peak about 1.5 hours post dosing.[22]

After oral administration, it was found that plasma concentrations of dihydrodydrogesterone were substantially heightened than those of the primary drug. The ratios of DHD and Dydrogesterone for AUC and Cmax are in the order of 40 and 25, respectively. Absolute bio-availability is on average 28%.[23]

All the metabolites of dydrogesterone retain the 4, 6-diene-3-one structure, and are metabolically stable. As such, dydrogesterone does not undergo aromatisation, which is consistent with its absence of estrogenic effects. Furthermore, dydrogesterone does not undergo 17α-hydroxylation, which explains its lack of androgenic effects.

Elimination and dependencies[edit]

Dydrogesterone and its metabolites are excreted predominantly in urine. Total clearance of plasma is at a rate of 6.4 L/min. Within 72 hours, excretion is virtually complete. DHD is preponderantly present in the urine as a conjugate of glucuronic acid. Approximately 85% of the oral dose is successfully egested from the body within 24 hours. The average terminal half-lives of DHD and dydrogesterone vary between 14–17 and 5–7 hours, respectively.

Dydrogesterone has predictable pharmacokinetics. The single-dose kinetics are linear in the oral dose range of 2.5–10 mg. The pharmacokinetics do not change during repeated administration of up to 20 mg dydrogesterone once daily. Steady state is attained after 3 days of treatment.[22]

In HRT, dydrogesterone is administered together with an estrogen. Therefore, the interaction between dydrogesterone and estrogens has been assessed, and no clinically significant interaction has been observed.


When administered orally Dydrogesterone has advantageous pharmacological properties compared to endogenous progesterone:[24]

  • It is orally active at low dosages.
  • It has selective progestogenic properties without any traditional hormonal activity.
  • The amount absorbed is more predictable than for progesterone, since it is not broken down as easily when passing through the digestive system.

Dydrogesterone is characterised by progestational and antiestrogenic activity.[25] This is demonstrated by its ability to induce a secretory transformation in the endometrium of immature or ovariectomised animals after they have been primed with estrogens (cf. the Clauberg test). The oral progestogenic potency of dydrogesterone is 20 times higher than that of progesterone.[26]

The progestational efficacy and potency of dydrogesterone was confirmed by standard test (i.e. delay of menses and induction of withdrawal bleeding). The benefits of estrogen or other target organs are not compromised by dydrogesterone.[27]

Unlike other synthetic progestogens, dydrogesterone is not chemically related to testosterone.[3] Its low affinity for the androgen receptor explains why it has no unwanted androgenic effects even at high doses and after prolonged treatment showed:

  • no virilisation (acne, voice changes, hirsutism) of the adult female
  • no virilising effects on the genital tract of the female foetus
  • no effect on the fertility of the offspring.

Dydrogesterone is not converted into estrogen, and has no adverse estrogenic effects on fertility or sexual development.

At recommended doses, dydrogesterone has no effect on ovulation in healthy women:

  • the biphasic pattern of the basal body temperature is maintained
  • normal ovulatory rise in estrogen and pregnanediol
  • normal premenstrual biopsy
  • no modification of vaginal cytology
  • cytological evidence of ovulation
  • the formation of the corpus luteum has been confirmed by laparotomy

These beneficial results are of particular relevance to the use of dydrogesterone in women who wish to become pregnant.


No severe or unforeseen toxicity have been accounted for with the use of dydrogesterone. In acute toxicity trials, the LD50 doses in rats were in excess of 4,640 mg/kg orally.[1]

The Ames test found no evidence of any potential mutagenic or toxicity properties.[1][28]

Adverse reactions and side effects[edit]

The most commonly reported drug related adverse reactions of patients treated with dydrogesterone without estrogen treatment in clinical trials of indications are migraines, headaches, nausea, menstrual disorders and breast pain or tenderness, bloating or weight gain.[29]

The use of progestins, in particular medroxyprogesterone acetate, in treating post-menopausal symptoms have been associated with increased risk of blood clots[30] and breast cancer in a study carried out by the Women's Health Initiative. While the study did not involve dydrogesterone, it is possible, but not certain, that it too increases these risks.[31]

See also[edit]


  1. ^ a b c "Dydrogesterone". DrugBank. 
  2. ^ a b "Dydrogesterone review". MedicaLook.com. 
  3. ^ a b c "What is Duphaston". PrescriptionMedications.in. 
  4. ^ "Dydrogesterone". Royal Society of Chemistry. 
  5. ^ Coelingh Bennink HJ, Boerrigter PJ. (2003). "Use of dydrogesterone as a progestogen for oral contraception.". PMID 14667985. 
  6. ^ "Pentavalent vaccines: Dydrogesterone Versus Intravaginal Progesterone in the Luteal Phase Support". ClinicalTrials.gov. 
  7. ^ Tabaste JL, Servaud M, Steiner E, Dabir P, Bene B, Pouzet M. (1984). "Action of dydrogesterone in postpubertal menstruation disorders". PMID 6531584. 
  8. ^ a b Dennerstein L, Morse C, Gotts G, Brown J, Smith M, Oats J, Burrows G. (1986). "Treatment of premenstrual syndrome. A double-blind trial of dydrogesterone.". PMID 2951407. 
  9. ^ Johnston WI. (1976). "Dydrogesterone and endometriosis". PMID 1252380. 
  10. ^ "Dydrogesterone/Estradiol Hormone Replacement Therapy". National Health Service. 
  11. ^ "Dydrogesterone". MedChemExpress. 
  12. ^ Trivedi P, Selvaraj K, Mahapatra PD, Srivastava S, Malik S. (2007). "Effective post-laparoscopic treatment of endometriosis with dydrogesterone.". PMID 17943543. 
  13. ^ Panay N, Pritsch M, Alt J. (2007). "Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study.". PMID 17891596. 
  14. ^ "A Comparative Study between Norethisterone Progestogens and Dydrogesterone in the Treatment of Dysfunctional Uterine Bleeding". Science Publications. 
  15. ^ Loose, Davis S.; Stancel, George M. (2006). "Estrogens and Progestins". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 1541–71. ISBN 0-07-142280-3. 
  16. ^ "Treatment of pain". ESHRE. 
  17. ^ "Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement". The Journal of Clinical Endocrinology and Metabolism. 
  18. ^ Mueck AO, Seeger H, Bühling KJ. (2009). "Use of dydrogesterone in hormone replacement therapy.". PMID 19836909. 
  19. ^ "Dydrogesterone (Duphaston®) and its 20-Dihydro-derivative as Selective Estrogen Enzyme Modulators in Human Breast Cancer Cell Lines. Effect on Sulfatase and on 17‚-Hydroxysteroid Dehydrogenase (17‚-HSD) Activity". Anticancer Research. 
  20. ^ "Use of Dydrogesterone as a progestogen for oral contraception". DeepDyveScienceDirect. 
  21. ^ "Duphaston Prescribing Information". Ministry of Health (Israel). 
  22. ^ a b "Duphaston 10mg Film-Coated Tablets". medicines.ie Ireland. 
  23. ^ "Femoston 2/10mg film-coated tablets". medicines.ie Ireland. 
  24. ^ "Classification and pharmacology of progestins". Maturitas. 
  25. ^ "Severity of Bleeding as a Predictor of Quality of Life (QoL) in Women With Heavy Menstrual Bleeding (HMB) Under Dydrogesterone Treatment". ClinicalTrials.gov. 
  26. ^ "Oral dydrogesterone versus intravaginal micronised progesterone as luteal phase support in assisted reproductive technology (ART) cycles: results of a randomised study.". ResearchGate. 
  27. ^ properties of the progestogen dydrogesterone "Classification and pharmacology of progestins". Maturitas. 
  28. ^ "DYDROGESTERONE". United States National Library of Medicine. 
  29. ^ "Dydrogesterone/Estradiol (Generic Femoston 1/10mg tablets)". National Health Service (England). 
  30. ^ "Femoston". NetDoctor.co.uk. 
  31. ^ "Questions and Answers About the WHI Postmenopausal Hormone Therapy Trials". Women's Health Initiative.