What is Dienogest?
Dienogest is a fourth-generation synthetic progestin (19-nortestosterone derivative) with potent antiandrogenic, antiproliferative, and anti-inflammatory properties, primarily used for treating endometriosis and as a component of combined oral contraceptives. 1, 2
Chemical Structure and Pharmacology
Dienogest is a C-19 progestogen with a cyanomethyl group at the C-17 position (instead of an ethinyl group), which may result in fewer hepatic effects compared to other 19-nortestosterone derivatives 1
It has high oral bioavailability exceeding 90% and a short plasma half-life of approximately 10 hours, preventing drug accumulation 1
Dienogest demonstrates higher progesterone receptor-binding affinity than natural progesterone itself, contributing to its strong endometrial efficacy 3
Unique Pharmacologic Properties
Dienogest combines characteristics of both C-19 progestogens and progesterone derivatives, giving it a distinctive clinical profile: 1
Antiandrogenic activity: Considerable antiandrogenic effects enhanced by its lack of affinity to sex hormone-binding globulin (SHBG), unlike other C-19 progestogens 1
Metabolic neutrality: No significant effects on metabolic or cardiovascular systems 1
Hormonal selectivity: No glucocorticoid, antimineralocorticoid, or antiestrogenic activity 1
Low gonadotropic activity: Does not suppress estradiol levels to zero (unlike GnRH analogues), maintaining beneficial estrogen effects while treating endometriosis 1
Clinical Applications
Endometriosis Treatment
Dienogest 2 mg daily is approved for endometriosis treatment in many countries and demonstrates efficacy comparable to GnRH agonists but with superior tolerability: 3, 2
Significantly reduces dysmenorrhea, premenstrual pain, dyspareunia, and diffuse pelvic pain after 24 weeks of treatment 3
Decreases endometrioma size progressively over 6 months (from mean 44 mm to 34.4 mm) 4
Most significant symptom improvement occurs within the first 3 months of treatment 4
Causes less bone mineral density loss compared to buserelin acetate (GnRH agonist) 3
Effective for long-term use (up to 65 weeks studied) with high patient compliance and low withdrawal rates 5
Contraceptive Use
Dienogest is combined with ethinyl estradiol or estradiol valerate in oral contraceptives: 6, 1
Combined with 17β-estradiol at 2 mg dienogest for continuous hormone replacement therapy in young women with premature ovarian insufficiency 6
The American Academy of Dermatology recognizes dienogest-containing combined oral contraceptives as effective for acne treatment 6
High endometrial efficacy provides excellent menstrual cycle stability when combined with estrogens 1
Safety Profile and Adverse Effects
The primary adverse effect is irregular bleeding (spotting or breakthrough bleeding), which typically decreases with continued treatment: 3
Predictable adverse effects with favorable overall safety and tolerability profile 5
No significant metabolic or cardiovascular effects due to its progesterone-derivative characteristics 1
Does not antagonize estradiol's beneficial effects due to lack of antiestrogenic activity 1