Dydrogesterone

Dydrogesterone: A Comprehensive Overview of a Key Progestogen in Women's Health

By Naeem Mustafa

pharmaservepk

December 19, 2025

Dydrogesterone, commonly known by its brand name Duphaston, is a synthetic progestogen that has been a cornerstone in gynecological and obstetric care since its introduction in the 1960s. Chemically, it is a retroprogesterone—a stereoisomer of natural progesterone—with a structure that allows for effective oral administration while minimizing unwanted effects on other hormone receptors.

Dydrogesterone

Compared to natural progesterone, dydrogesterone's retro configuration enhances its selectivity for progesterone receptors, reducing androgenic, estrogenic, or glucocorticoid side effects common with older synthetic progestins.

Typical packaging of Duphaston includes 10 mg tablets in blister packs, widely used globally.

Mechanism of Action

Dydrogesterone binds selectively to progesterone receptors, mimicking natural progesterone to induce secretory changes in the endometrium. This supports implantation and maintains pregnancy in progesterone-deficient states. Unlike some progestins, it does not inhibit ovulation at standard doses and has minimal cross-reactivity with other receptors, contributing to its favorable tolerability profile.

Primary Uses

Dydrogesterone is prescribed for progesterone-related conditions:

Threatened or recurrent miscarriage: Provides luteal support to prevent early pregnancy loss.

Luteal phase support in assisted reproductive technology (ART/IVF): Oral alternative to vaginal progesterone.

Menstrual disorders: Irregular cycles, dysmenorrhea, abnormal uterine bleeding, and premenstrual syndrome.

Endometriosis: Reduces pain and lesion growth.

Hormone replacement therapy (HRT): Combined with estrogens in menopause to protect the endometrium.

Infertility due to luteal insufficiency.

Recent studies (2024–2025) confirm its efficacy in reducing miscarriage rates in threatened cases, with network meta-analyses showing oral dydrogesterone superior to placebo and sometimes vaginal progesterone in preventing miscarriage.

Efficacy in Pregnancy Support

Extensive data support dydrogesterone's role in miscarriage prevention. Systematic reviews and meta-analyses indicate:

Significant reduction in miscarriage risk for threatened miscarriage (odds ratio ~0.5 vs. placebo).

Comparable or superior outcomes to micronized vaginal progesterone in IVF luteal support, with higher patient satisfaction due to oral route.

In recurrent early pregnancy loss, real-world data from 2025 show low miscarriage rates (7.7%) with extended-release formulations.

A 2025 network meta-analysis reinforced oral dydrogesterone's effectiveness over vaginal forms for first threatened miscarriage.

Side Effects and Tolerability

Common mild side effects include:

Breakthrough bleeding or spotting

Headache, nausea

Breast tenderness

Dizziness (rare)

Oral administration avoids vaginal irritation or discharge associated with progesterone gels/pessaries, improving compliance. Studies consistently report better tolerability than vaginal micronized progesterone.

Safety Profile and Recent Controversies

Dydrogesterone has a long-established safety record, with over 147 million exposures and 20+ million successful pregnancies. Multiple systematic reviews (up to 2024) found no increased risk of congenital anomalies compared to natural progesterone or controls, with anomaly rates around 2.5%.

However, a January 2025 pharmacovigilance analysis of WHO's VigiBase database reported disproportionate signals for birth defects (mainly hypospadias and congenital heart defects) with dydrogesterone versus progesterone or other drugs. This observational study highlighted higher reporting odds ratios (e.g., 5.4 vs. progesterone).

Critics and commentaries (2025) argue this reflects reporting bias, under-reporting of non-events, selection bias (e.g., higher-risk pregnancies), and confounding factors rather than causality. Clinical trials and meta-analyses show no such risk, and experts emphasize pharmacovigilance signals require verification through higher-evidence studies. No regulatory changes have restricted its use as of late 2025, and it remains widely recommended when indicated.

Comparison with Micronized Progesterone

Randomized trials and meta-analyses show:

Equivalent efficacy in pregnancy rates and miscarriage prevention.

Oral dydrogesterone often preferred for convenience and fewer local side effects.

Similar maternal and fetal safety in controlled settings.

Dydrogesterone remains a valuable, patient-friendly option in reproductive medicine, offering effective oral progestogen support with a strong evidence base for efficacy. While 2025 pharmacovigilance data raised questions about fetal safety, these are likely artifactual, as contradicted by robust clinical evidence. Prescribers should weigh benefits against individual risks, under medical supervision. Ongoing research will further clarify its role in modern obstetrics and gynecology.

Always consult a healthcare professional for personalized advice.

Published on pharmaservepk by Naeem Mustafa