How Gestrinone Affects HDL Cholesterol
Gestrinone, a 19-nortestosterone derivative used for endometriosis and sold in Brazil as a beauty-chip implant, lowered HDL by 25-41% across oral trials. Total cholesterol and triglycerides can fall at the same time, which hides the damage.
The Mechanism
Gestrinone is an androgen as well as an antiprogestogen and antiestrogen. Its HDL effect follows the usual androgen pathway:
- Hepatic lipase upregulation: androgen signalling in the liver increases hepatic lipase activity, which breaks down HDL particles faster.
- ApoA-I reduction: ApoA-I, the main HDL protein, fell 31% in a Japanese study, so fewer new HDL particles are made.
- Low estrogen: gestrinone keeps estradiol in the early follicular range or lower. Estrogen normally supports HDL in women, so that support is lost.
The same studies show triglycerides, VLDL and Lp(a) falling. That makes the total cholesterol line look better while the HDL to LDL balance gets worse.
Expected Changes
Oral 2.5 mg twice weekly for 6 months (endometriosis trials):
- HDL down 25% vs no change on leuprorelin (Gestrinone Italian Study Group 1996, n=27)
- HDL down 40% at both 1.25 mg and 2.5 mg twice weekly, with LDL up 13% (Worthington 1993, n=20)
- HDL down 41%, ApoA-I down 31%, LDL to HDL ratio up 92% at 5-10 mg/week (Fukuda 1989, n=12)
Example: a woman starting at 1.5 mmol/L (58 mg/dL) would expect roughly 0.9-1.1 mmol/L (35-43 mg/dL) after six months on the oral dose.
Implants: no published lipid data. Compounded "chip da beleza" pellets have unknown doses, and many were combined with testosterone or oxandrolone, so drops beyond 40% are possible.
Recovery: lipids were back to baseline 6 months after stopping oral gestrinone in a 56-woman Chinese study (Zheng 2005). There is no data after implant removal.
Monitoring Guidance
- Baseline: full lipid panel with HDL, LDL and ApoB before the first dose or implant
- Weeks 6-8: repeat the lipid panel with ApoB
- Every 3 months while on it
- 3 and 6 months after stopping or removal
Read HDL together with ApoB and the LDL to HDL ratio. Do not judge the result by total cholesterol, which often falls on gestrinone.
Management Strategies
- An HDL drop of 25-40% is expected on the oral dose. A drop beyond 40%, or a rising ApoB, is a reason to discuss stopping or implant removal
- Check what else was in the implant. Combined gestrinone and testosterone or oxandrolone pellets were common in Brazil
- Cardio, omega-3s and avoiding other androgens help at the margins, but the drug is the cause
- There is no evidence that HDL-raising supplements offset an androgen-driven drop
Full evidence review: Does gestrinone work for endometriosis?
Clinical Significance
A 25-41% HDL fall with rising LDL and ApoB is a consistent finding across gestrinone trials. Over months to years on an implant, this is the main cardiovascular cost.
Frequently Asked Questions
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Quick Facts
Effect Direction
Severity
Dose-Dependent
Reversible