Progestogens — pregnadiene derivatives
ATC code: G03DB01 (Dydrogesterone)
Brand names
Duphaston
Semi-synthetic progestogen, a progesterone isomer at the double bond. Selectively binds progesterone receptors with no estrogenic, androgenic, or mineralocorticoid activity. Unlike micronized progesterone, lacks sedative and anxiolytic effects (no allopregnanolone metabolite) — taken at any time of day.
First line
Per NAMS 2022 and IMS 2016, dydrogesterone 5–10 mg daily or 10 mg for 14 days per month provides endometrial protection during estrogen MHT. The breast cancer and VTE risk profile of dydrogesterone is closer to micronized progesterone than to synthetic progestins such as medroxyprogesterone acetate. Fixed combination with estradiol is available as Femoston.
First line
The Lotus I and Lotus II trials showed oral dydrogesterone 30 mg daily was non-inferior to vaginal micronized progesterone for live birth rates in ART. 2019 endorsed oral dydrogesterone as an alternative for luteal phase support.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Dydrogesterone has variable evidence for dysmenorrhea and endometriosis. For pain unrelated to menstrual cycle or endometriosis, dydrogesterone is not indicated. Common Russian prescriptions for Duphaston for «hormonal imbalance», «cycle disturbance» without workup, or «luteal-phase progesterone deficiency on blood levels» lack international evidence and often mask missed differential diagnoses.
Dydrogesterone is labeled for dysmenorrhea, not «any lower abdominal pain».
Not recommended
Prescribing dydrogesterone (Duphaston) for threatened miscarriage in patients without recurrent loss is one of the most widespread misuses in Russia and the CIS. In most patients, the cause is embryonic chromosomal abnormality, and progestogens do not prevent pregnancy loss. The 2018 Cochrane review did not confirm efficacy in this population. A narrow subgroup with prior recurrent loss and current threatened miscarriage may see a small benefit (PRISM, NEJM 2019: 3 % increase in live births). Routine mass prescription of Duphaston for all patients with cramping or spotting in the first trimester is a marketing-driven practice without an evidence base.
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Use in the first and second trimesters for ART or recurrent loss indications is acceptable. Without specific indication, routine pregnancy use is unjustified.
Transfers into milk in minimal amounts. Compatible with breastfeeding.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Dydrogesterone is evaluated for the following indications with varying evidence strength: Luteal phase support in ART (evidence tier A), Endometrial protection during estrogen MHT (evidence tier A), Irritable bowel syndrome (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Dydrogesterone (≥ 1 in 100): Headache, Breast tenderness, Breakthrough bleeding, Nausea, Mood changes. See the Safety section for uncommon and serious reactions.
FDA category B. Use in the first and second trimesters for ART or recurrent loss indications is acceptable. Without specific indication, routine pregnancy use is unjustified.
Transfers into milk in minimal amounts. Compatible with breastfeeding.
Dydrogesterone is contraindicated in: Hypersensitivity; Undiagnosed vaginal bleeding; Progestogen-dependent (or suspected) tumors; Severe hepatic disease. Full list in the Safety section.
in patients without recurrent loss, evidence is lacking. Cramping and spotting more often reflect physiological processes than embryonic chromosomal abnormality.
the laboratory diagnosis of «progesterone deficiency» does not exist in international gynecology. Progesterone levels vary throughout the day and menstrual cycle. Endocrine causes of anovulatory infertility are diagnosed with other approaches — follicle tracking, hormone panels by clinical picture, extended workup as indicated.
in anovulation, luteal-phase progesterone is physiologically low because no corpus luteum formed. A progestogen does not treat the cause of anovulation. Management requires identifying the cause (PCOS, hypothalamic dysfunction, hyperprolactinemia, thyroid dysfunction, etc.).