Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library
Nafarelin (Synarel): what the evidence says
At a glance
What it is: a synthetic 10-amino-acid GnRH analog (with an unusual naphthylalanine amino acid) given as a nasal spray. Approved as Synarel (Feb 1990) for endometriosis and central precocious puberty. R1, R2
What the evidence says: Human in a double-blind trial of 307 women, nafarelin relieved endometriosis as well as danazol, with more hot flushes but less weight gain; a smaller trial agreed. R3, R4 Precocious-puberty trials were not reviewed for this page. UNVERIFIED
Biggest risks: low-estrogen effects such as hot flashes and loss of bone mineral; nasal irritation in about 1 in 10 users. Prohibited in male athletes. R2, R5
Rating
| Human Human evidence | Moderate: older RCTs vs danazol R3, R4 |
| Animal Animal / lab evidence | Not reviewed |
| Regulatory | FDA-approved R1 · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page R6, R7, R8 · prohibited in male athletes (WADA S2.2.1) R5 |
| Established human dose | Yes, label dose (see Study details) |
Evidence verdict: Endometriosis: Moderate (older danazol-controlled RCTs) · Central precocious puberty: approved (trials not reviewed here) · Off-label hormone use: No human data
This page reports what studies used. It is not dosing advice.
Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source
About the evidence: older comparative trials, no placebo control in those reviewed.
What is it?
Related pages: goserelin, histrelin, leuprolide, triptorelin.
Does it work?
- Human Endometriosis: similar effectiveness to danazol. R3, R4
- ⚪ Precocious puberty: approved; trials not reviewed here.
Is it safe?
- Hot flashes, headaches, emotional lability, reduced libido and vaginal dryness; repeat courses not advised with major bone-loss risk factors. R2
- Nasal irritation in about 10% of users. R2
Gray-market vials: extra risks
A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.
Is it legal?
- US: FDA-approved, prescription (Synarel). R1
- Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. R6, R7, R8
- Sport: prohibited at all times in male athletes; WADA names it among the GnRH analogues under S2.2.1. R5
Study details
Study details
These are amounts researchers used, not recommendations.
| Study | People / model | Route | Amount used | Follow-up | Reported | Citation |
|---|---|---|---|---|---|---|
| NEET 1992 (double-blind) | 307 women with endometriosis | Nasal | Per study | 6 months + 1-yr follow-up | Equal to danazol; more hot flushes, less weight gain | PMID 1531464 |
| Cheng 2005 | 59 women with endometriosis | Nasal | Per study | 180 days | Similar to danazol; fewer lab changes | PMID 16038370 |
Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)
- R1 Drugs@FDA, Synarel (nafarelin), application NDA019886 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA019886
- R2 Synarel prescribing information, label published Mar 5, 2026 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0aa57cb-d2f4-46d7-af43-7c8b06aa81a6
- R3 Anon. Fertil Steril. 1992. PMID 1531464
- R4 Cheng MH, et al. J Chin Med Assoc. 2005. PMID 16038370
- R5 WADA. The 2026 Prohibited List, S2.2.1, Chorionic Gonadotrophin and Luteinizing Hormone and their releasing factors, naming goserelin, histrelin and nafarelin among the GnRH analogues (prohibited in males). https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
- R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
- R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
- R8 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
Disclaimer
This page is for education and harm reduction, not medical advice or a recommendation to use Nafarelin (Synarel). This is a prescription medicine. Use it only under the care of a licensed clinician; do not buy it from research-chemical or gray-market sellers. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).