Orals

Gestrinone

Updated · 25 sources · Editorial policy

Gestrinone (code name R-2323, also called ethylnorgestrienone) is a synthetic steroid derived from 19-nortestosterone. It has a mixed hormonal profile: it acts as an antiprogestogen and antiestrogen, it suppresses the pituitary signals that drive the ovaries, and it has clear androgenic activity. It was first studied in the 1970s as a long-acting contraceptive It was later marketed as an oral treatment for endometriosis in Europe, Latin America and Australia from the 1980s (Fagundes et al., Pharmaceutics 2025).

The single most important fact: gestrinone has never been approved in the US, and in Brazil, where off-label implant use has drawn regulatory action, no gestrinone product is currently registered. Most current use is off-label, through compounded subcutaneous implants marketed for body composition and “aesthetic” purposes, a use for which no controlled trials exist. Gestrinone is also the parent compound of the designer steroid THG and is banned in sport.

This page summarizes what the clinical trials, systematic reviews and regulators report. It is for education only and is not medical advice.

Property Detail
Drug class Synthetic 19-nortestosterone derivative; antiprogestogen with antiestrogenic and androgenic activity
Other names R-2323, ethylnorgestrienone
Former approved use Oral treatment of endometriosis (outside the US)
Routes studied Oral capsules, vaginal tablets, subdermal implants
Doses in endometriosis trials 1.25–2.5 mg orally twice weekly for 6 months
Half-life Around 24 h after oral dosing, per a 2025 trial-design paper; no full human pharmacokinetic study is indexed
US status Not FDA-approved; not named in the DEA Schedule III list
Brazil status Two oral registrations canceled in 2012 and 2014; none currently registered
WADA status Prohibited at all times (S1.1 anabolic androgenic steroids)

What it is

Gestrinone has the formula C₂₁H₂₄O₂ and a molecular weight of 308.4 g/mol (PubChem). Its key structural features are a 13-ethyl group, a 17α-ethynyl group and three double bonds in the steroid rings (positions 4, 9 and 11). Trenbolone has the same 4,9,11-triene ring system (21 CFR 1308.13); see trenbolone acetate.

Gestrinone belongs to the 17α-ethynyl family of progestins, alongside norethisterone, ethisterone and norgestrel. In a yeast-based bioassay that screened commercially available progestins, this family had the strongest built-in androgenic activity of all the marketed progestins tested (McRobb et al., J Steroid Biochem Mol Biol 2008). The same study showed that small chemical changes to the 17α-ethynyl group of these progestins can produce still more potent androgens.

That is exactly how THG was made. The UCLA laboratory that identified THG in a syringe linked to the BALCO doping case synthesized reference THG by hydrogenating gestrinone (Catlin et al., Rapid Commun Mass Spectrom 2004).

Compound Relationship Status
Gestrinone 19-norsteroid progestin with a 17α-ethynyl group Formerly marketed for endometriosis outside the US
THG Gestrinone with the 17α-ethynyl group reduced to ethyl Designer steroid, never a medicine
Danazol A different synthetic steroid; the main comparator in gestrinone endometriosis trials See its own page

How it works in the body

Gestrinone acts on several hormone systems at once:

  • Steroid receptors. In human endometrial tissue it bound estrogen, progesterone and androgen receptors, but not sex hormone-binding globulin (SHBG) (Tamaya et al., Acta Obstet Gynecol Scand 1986).
  • Pituitary–ovarian axis. It blocks the mid-cycle surge of the pituitary hormones LH and FSH, which prevents ovulation and stops periods (Malavasi et al., Ann Med 2025). In 11 women given 2.5 mg twice weekly for 6 months, LH, FSH and estradiol stayed in the early-cycle (follicular) range, total testosterone and SHBG fell, and free testosterone rose slightly (Venturini et al., Fertil Steril 1989). The authors concluded that it has antiestrogenic, androgenic and progestogenic effects at therapeutic doses.
  • SHBG. In a small study of 7 women on gestrinone 5 mg/week, SHBG binding capacity fell from 56.4 to 7.1 nmol/L after 4 weeks (Dowsett et al., Clin Endocrinol 1986). Less SHBG means a larger share of testosterone circulates unbound and active, which contributes to androgenic side effects.

The net clinical result is suppressed ovulation, a thin (atrophic) endometrium and often no periods (amenorrhea).

Pharmacokinetics

Human pharmacokinetic data are sparse. A 2025 trial-design paper states that oral gestrinone has a serum half-life of around 24 h, is metabolized in the liver mainly by hydroxylation, and that its conjugates are excreted in urine (40–45%) and feces (30–35%) (Malavasi et al., Ann Med 2025). The paper cites a urine-metabolite study for these figures, and we could not find a full published human pharmacokinetic study that reports them directly. Treat the 24 h figure as approximate.

Even so, the trials gave oral gestrinone only two or three times a week rather than daily. No pharmacokinetic study of the bioabsorbable pellets now used in Brazil has been published; the GLADE trial planned to measure pellet pharmacokinetics in 15 participants (Malavasi et al., 2025).

Former medical uses

Gestrinone was first developed as a contraceptive. Silastic (silicone) implants containing 30–40 mg each were tested in 531 women in the 1970s (Coutinho et al., Contraception 1975). A Chilean trial in 38 women with six 30 mg implants recorded no pregnancies over 292 months of exposure. However, acne, excess body hair, headache and nervousness were common, and liver enzymes (transaminases) rose in 20 of 27 women after 3 months (Diaz et al., Contraception 1977). All of these effects resolved after the implants were removed. Gestrinone did not become an established contraceptive.

Its main approved use was oral treatment of endometriosis, in which tissue resembling the uterine lining grows outside the uterus and causes pain and infertility. The usual trial dose was 2.5 mg twice weekly for 6 months.

In Brazil, two oral gestrinone products for endometriosis were registered with the national regulator ANVISA. Their registrations were canceled in 2012 and 2014, and no gestrinone product is currently registered there (Amato et al., Cureus 2025). The same review notes that gestrinone is not approved or marketed in the US.

What the research shows

Endometriosis: comparison with danazol and leuprorelin

The 2026 update of the Cochrane review of progesterone receptor modulators included four gestrinone trials (Grammatis et al., Cochrane 2026). It rated the certainty of all gestrinone evidence as low to very low.

Comparison (6 months) Outcome Result
Gestrinone vs danazol (2 trials, 302 women) Overall pain, dysmenorrhea, dyspareunia Uncertain; one trial with 38 women gave estimable data
Gestrinone vs danazol Hot flushes OR 0.79 (95% CI 0.50–1.26)
Gestrinone vs danazol Nausea OR 1.36 (95% CI 0.84–2.19)
Gestrinone vs leuprorelin (1 trial, 55 women) Dysmenorrhea score Higher (worse) on gestrinone: MD 0.82 (95% CI 0.15–1.49)
Gestrinone vs leuprorelin Dyspareunia score Lower (better) on gestrinone: MD −1.16 (95% CI −2.08 to −0.24)
Gestrinone vs leuprorelin Non-menstrual pain No clear difference: MD −0.41 (95% CI −1.76 to 0.94)
Gestrinone vs leuprorelin Hot flushes Fewer on gestrinone: OR 0.20 (95% CI 0.06–0.63)

The individual trials behind these numbers:

  • Danazol, European multicenter trial. A double-blind trial randomized 269 women to danazol 200 mg twice daily or gestrinone 2.5 mg twice weekly for 6 months (Bromham et al., BJOG 1995). At repeat laparoscopy, disease scores improved by 73.3% on gestrinone and 72.7% on danazol. Both groups gained weight significantly. Hirsutism (excess body hair) was more common on gestrinone, and leg cramps on danazol.
  • Danazol, Brazilian trial. An open-label trial of 164 women found no significant difference in disease scores or symptom response. Danazol was better than gestrinone for acne and irregular bleeding (Halbe et al., BJOG 1995).
  • Leuprorelin (leuprolide), Italian trial. A double-blind, double-dummy trial randomized 55 women with moderate or severe pelvic pain to oral gestrinone or a monthly depot GnRH agonist for 6 months (Gestrinone Italian Study Group, Fertil Steril 1996). Pain improved in both arms. During follow-up, moderate or severe pain returned in 2 of 17 women (11.8%) on gestrinone vs 9 of 17 (52.9%) on leuprorelin (OR 0.12, 95% CI 0.02–0.69).

A 2023 meta-analysis of 16 studies with 1,286 women concluded that gestrinone “appeared to be safe” and may have advantages over danazol, but that the quality of evidence was “very low or unclear” (de Souza Pinto et al., Arch Gynecol Obstet 2023). Several of its authors are affiliated with companies that make drug-releasing implants.

Dose: 1.25 mg vs 2.5 mg

Two small double-blind trials compared 1.25 mg and 2.5 mg twice weekly for about 6 months:

Trial n Disease score Bone and lipids
Worthington et al., Fertil Steril 1993 20 Fell with both doses (median 7.5 to 1.0 and 7.0 to 0); no difference between doses Spine and hip bone density preserved; LDL up 13%, HDL down 40%
Dawood et al., Am J Obstet Gynecol 1997 11 Fell significantly with 2.5 mg (10.3 to 3.8); 2.5 mg judged more effective Spinal bone up 7.1% on 2.5 mg but down 7.1% on 1.25 mg; not fully reversed 6 months after stopping

Uterine fibroids

In a randomized study of 97 women with fibroids, oral gestrinone (5 mg twice weekly or 2.5 mg three times weekly) shrank the uterus over 4–13 months, while vaginal 2.5 mg tablets did not (Coutinho et al., Am J Obstet Gynecol 1986). After 4 months, 95% of women had no periods, and hemoglobin rose in 85 of 90.

Muscle, body composition and “aesthetic” use

No controlled human trial has tested gestrinone for muscle gain, fat loss, athletic performance, menopause symptoms or lipedema.

  • A 2025 systematic review found no studies of any design on gestrinone for lipedema, a condition of abnormal fat buildup in the legs. Professional societies uniformly advise against it (Amato et al., Cureus 2025).
  • A 2025 systematic safety review found no clinical safety data at all for gestrinone in men (Fagundes et al., Pharmaceutics 2025).
  • A 2024 review that proposes wider use of gestrinone implants (for menopause, lipedema and sarcopenia) acknowledges that evidence on dose and safety is limited. It was funded by an implant manufacturer, and its lead author works for that company (Renke et al., Pharmaceuticals 2024).

The only placebo-controlled implant trial, GLADE, randomized 100 women with deep endometriosis to an 85 mg bioabsorbable gestrinone pellet or placebo, with serious adverse events as the primary endpoint (Malavasi et al., Ann Med 2025). ClinicalTrials.gov lists it as completed, with no results posted as of its last update in June 2026 (NCT05570786).

Side effects and risks

Androgenic effects

Androgenic effects are the most typical problems. The 2025 safety review pooled 32 clinical trials, all in women (Fagundes et al., Pharmaceutics 2025):

Adverse effect Share of reports or patients
Acne and seborrhea (oily skin) 42.7%
Amenorrhea 41.4%
Decreased libido 26.5%
Hot flushes 24.2%
Breast size reduction 23.7% (8 trials)
Cramps 18.6%
Raised liver enzymes 15.1% (4 trials)
Hoarseness 3.5%
Weight gain Reported in 24 studies; 0.9–8 kg per patient

In the large European danazol comparison, 4 women stopped gestrinone because of hirsutism (Bromham et al., BJOG 1995).

Lipids

Gestrinone lowers HDL (“good”) cholesterol substantially:

Liver

Transaminase rises appeared in 20 of 27 women with high-dose contraceptive implants (Diaz et al., 1977) and in 15.1% of patients across the four trials that reported them (Fagundes et al., 2025). In the implant study, the rises resolved after removal.

Bone

Results on bone density are mixed. Spine and hip density was preserved at both 1.25 mg and 2.5 mg in one trial (Worthington et al., 1993). In the leuprorelin comparison, lumbar density rose slightly on gestrinone but fell by 3% on leuprorelin (Gestrinone Italian Study Group, 1996). But another small trial found a 7.1% spinal loss at 1.25 mg twice weekly (Dawood et al., 1997).

Suppression of testosterone in men

Data in men are minimal. In a 1977 study of 10 men aged 31–72, gestrinone 100 mg weekly for 6 weeks caused a sharp fall in testosterone, LH and FSH (Frick et al., Urol Res 1977). Hormone levels were back to normal in 80% of the men 6 weeks after stopping.

Pregnancy

Gestrinone has androgenic activity, and androgen exposure can virilize a female fetus. The GLADE trial-design paper states that it was embryotoxic in animals, with a risk of androgenizing female fetuses (Malavasi et al., 2025). Pregnancies occurred during contraceptive implant use (Coutinho et al., 1975), so gestrinone cannot be assumed to be a reliable contraceptive.

Compounded implants

In Brazil, compounding pharmacies have made hormone implants, including the so-called “beauty chip,” without authorization from regulators (Fagundes et al., 2025). Compounded gestrinone pellets lack strict dosage control, and compounded pellets in general face problems with dose accuracy, release consistency and sterility (Wender et al., Rev Assoc Med Bras 2025). That review describes the evidence on gestrinone pellets as very limited and of very low quality.

  • United States. Not approved or marketed (Amato et al., 2025). Gestrinone is not named in the federal Schedule III list of anabolic steroids, which does name its derivative THG (21 CFR 1308.13).
  • Brazil. According to two 2025 reviews, ANVISA banned advertising of gestrinone and gestrinone products in 2021, and the Federal Council of Medicine’s Resolution 2,333/2023 prohibited prescribing hormone therapies such as these for aesthetic purposes (Fagundes et al., 2025; Wender et al., 2025).
  • Sport. Gestrinone is named on the WADA Prohibited List under S1.1 anabolic androgenic steroids, prohibited at all times (WADA 2026 Prohibited List).

Key takeaways

  • A progestin with real androgenic activity. Gestrinone is a 19-nortestosterone derivative that suppresses ovarian function, lowers SHBG and raises free testosterone. Its close relative THG was made from it by a single chemical step.
  • Modest, low-certainty evidence in endometriosis. In small, older trials it performed broadly like danazol, and was worse for period pain but better for pain during sex than leuprorelin. Cochrane rates this evidence as low to very low certainty.
  • No evidence for body-composition use. No controlled trial supports gestrinone implants for muscle, fat loss, menopause or lipedema, and there are no clinical safety data in men.
  • Androgenic and lipid side effects are common. Acne or oily skin was reported in about 43% of cases, and HDL fell by 25–40% in trials.
  • Not an approved drug in the US or Brazil today. It was never approved by the FDA, its Brazilian registrations were canceled in 2012 and 2014, and it is prohibited in sport.

Sources

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