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Dydrogesterone ball-and-stick.png
Systematic (IUPAC) name
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
Pharmacokinetic data
Bioavailability 28%
Metabolism complete, 20-dihydrodydrogesterone (DHD) metabolite
Half-life dydrogesterone (5-7 hours) & DHD (14-17 hours)
CAS number 152-62-5 YesY
ATC code G03DB01
PubChem CID 9051
DrugBank DB00378
ChemSpider 8699 YesY
Chemical data
Formula C21H28O2 
Molecular mass 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), also known as 9β,10α-pregna-4,6-diene-3,20-dione, is a steroidal progestin. It is sold under the brand name Duphaston, which is manufactured by Abbott (formerly Solvay Pharmaceuticals).

Dydrogesterone was first introduced to the market in 1961, and is currently approved in over 100 countries worldwide. It has an estimated cumulative exposure of more than 10 million pregnancies.

Dydrogesterone is a potent, orally active progestogen indicated in a wide variety of gynaecological conditions related to progesterone deficiency. Although similar in molecular structure and pharmacological effects to endogenous progesterone. It is orally active at far lower doses. Its freedom from estrogenic, androgenic, anabolic, corticoid and other undesirable hormonal effects gives it additional benefits over most other synthetic progestogens.

The therapeutic use of dydrogesterone is closely related to its physiological action on the neuro-endocrine control of ovarian function, as well as on the endometrium. As such, it is indicated in all cases of relative or absolute endogeneous progesterone deficiency.

Dydrogesterone is to be withdrawn from the UK market from March 2008 for commercial reasons. Dydrogesterone was licensed for use in several indications,including threatened or recurrent miscarriage, dysfunctional uterine bleeding, and hormone replacement therapy.

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

Dydrogesterone has also been registered as hormone replacement therapy (HRT) to counteract 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.


Menstrual disorders[edit]


Primary or essential dysmenorrhoea is one of the most common gynaecological complaints of women during their reproductive years. Clinical studies have shown symptom relief and a reduction in pain with dydrogesterone treatment for dysmenorrhoea. (Aydar 1965, Fairweather 1963, Schellen 1967)

Secondary amenorrhoea

Secondary amenorrhoea is a symptom rather than a specific disease. Dydrogesterone adequately induces bleeding when the endometrium is sufficiently primed with estrogens. When estradiol levels are low, dydrogesterone treatment should be supplemented with estrogens.

Dysfunctional uterine bleeding and irregular cycles

Of the wide range of medications used to reduce heavy menstrual bleeding in patients with ovulatory cycles, oral progestogens like dydrogesterone are the most commonly prescribed. It prevents heavy bleeding.

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.[1]


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.

Premenstrual syndrome[edit]

Premenstrual syndrome (PMS) is characterised by a range of mood swings and physical symptoms.

Dydrogesterone effectively relieves a number of these.

Hormone replacement therapy[edit]

The principle behind HRT is twofold:

  • to actively increase the circulating levels of estrogens to control hot flushes
  • 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.

Estrogens stimulate the growth of endometrial cells. In postmenopausal women with an intact uterus, estrogen monotherapy results in continued endometrial proliferation without the physiological secretory transformation normally induced by progesterone. This process is associated with an increased incidence of endometrial hyperplasia and carcinoma. Additional protection with progestogens is therefore mandatory in patients with an intact uterus who receive estrogen replacement therapy.

Dydrogesterone opposes the proliferative effect of estrogens on the endometrium and ensures conversion to a secretory pattern and cyclical shedding of the endometrium in sequential HRT regimens. As such dydrogesterone effectively guards against the development of endometrial hyperplasia. Unlike androgenic progestogens, dydrogesterone does not reverse the beneficial effects of 17β-oestradiol on lipid profiles and carbohydrate metabolism. In a continuous combined HRT regimen, dydrogesterone inhibits the proliferation of the endometrium so that it remains atrophic or inactive.


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. 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.


Dydrogesterone is readily absorbed after oral administration. Tmax values vary between 0.5 and 2.5 hours.

Metabolisation of dydrogesterone is virtually complete. The main metabolic reaction is hydrogenation of the 20-keto group, resulting in 20-dihydrodydrogesterone (DHD), another potent progestogen. The levels of the main active metabolite DHD also peak about 1.5 hours after dosing.

After oral administration, plasma concentrations of DHD are substantially higher than those of the parent drug. The ratios of DHD/Dydrogesterone for AUC and Cmax are in the order of 40 and 25, respectively. Absolute bio-availability is on average 28%.

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.

Dydrogesterone has predictable pharmacokinetics. The single-dose kinetics are linear in the oral dose range of 5–20 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.

Dydrogesterone and its metabolites are excreted predominantly in urine. About 85% of an oral dose is excreted within 24 hours. The mean terminal half-lives od dydrogesterone and DHD vary between 5-7 and 14–17 hours, respectively.

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:

  • 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. 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.

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.

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

  • 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 serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640 mg/kg for the oral route.

There was no evidence of mutagenic potential in the Ames test.

Adverse reactions and side effects[edit]

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

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

See also[edit]


  1. ^ 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.