Nafarelin
GnRH agonist
Also Synarel, Nafarelin acetate, Synarel nasal spray, Synarela, RS-94991
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Nasal
- Studies cited
- 1 human0 animal or cell
A nasal spray that lowers hormones to treat endometriosis and early puberty in children. Controlled trials found it eased endometriosis about as well as the older drug danazol.
Sold for
Nafarelin is a prescription hormone suppressant for endometriosis and early puberty, with little of the online wellness market around it.
Studies say
Randomized trials showed nafarelin shrank endometriosis lesions and relieved pain about as well as danazol, with a different side effect profile, which is the basis of its approval and its A grade.
Why grade A. The approval rests on randomized double-blind trials against danazol, the standard endometriosis drug of the 1980s. The largest in these citations enrolled 213 women with laparoscopically confirmed endometriosis and judged lesions before and after treatment by repeat laparoscopy. What is missing is modern long-term data; the trials are old, and there is nothing here on use beyond the labeled indications. 12
FDA. Approved. Nafarelin is sold as Synarel, a metered nasal spray, for the management of endometriosis and for central precocious puberty in children. 2
Written from 3 cited sources. Fact-checked 2026-10-27: 14 claims checked, 2 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Endometriosis and early puberty
- Can a US doctor prescribe it?
- Yes, FDA approved for endometriosis and early puberty in children.
- Properly tested in people?
- Yes, in controlled trials; the largest covered 213 women.
Evidence checklist
- Randomised controlled trial Randomized double-blind versus danazolyes
- Human study over 100 people 213 women in the largest trialyes
- More than one research group Trials from the 1980s era sponsorsno information
- Clinical outcomes, not surrogate markers Laparoscopic lesion scoringyes
- Human safety data beyond case reports Label data and trial adverse eventsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Nafarelin is a synthetic analog of gonadotropin-releasing hormone (GnRH), the hormone the hypothalamus releases in pulses to tell the pituitary to make the sex hormones LH and FSH. It is roughly 200 times as potent as the natural hormone and is a nasal spray, where most drugs in its class are injected, which set it apart when it reached the market. 12
Pfizer sells it as Synarel. The two labeled uses are endometriosis in adults, where the goal is to reduce lesions and pain, and central precocious puberty in children, where the goal is to stop puberty that has started too early. 2
How it works
A GnRH agonist works by overdoing the signal. Natural GnRH arrives in pulses, and the pituitary responds to pulses. Nafarelin provides a continuous signal instead, so after a brief rise in LH and FSH the pituitary receptors shut down and hormone output falls. In adult women this drops estrogen to the range seen after menopause, and endometriosis tissue, which depends on estrogen, regresses. In children the same shutdown halts the hormonal drive behind early puberty. 12
What human research shows
The endometriosis trial randomized 213 women to nasal nafarelin or oral danazol for a six-month course, with placebo sprays and capsules to keep the comparison blind. Laparoscopy before and after treatment, scored with the American Fertility Society system, showed comparable reductions in disease extent for both drugs. Symptom relief was similar too: the share of women with severe pain fell from about 40% to 5 to 10%. The two drugs differed in side effects: danazol lowered HDL cholesterol and raised LDL cholesterol, which nafarelin did not, while more nafarelin users reported hot flashes and decreased libido. 1
In central precocious puberty, the label describes suppression of LH response and of sex hormone levels, with slowing of bone age advancement, as the basis for approval. These data come from uncontrolled series in children, because a placebo-controlled trial of untreated early puberty would not be ethical. 2
| Study | Model | Finding |
|---|---|---|
| Henzl 1988 nafarelin vs danazol | Humans, n=213, randomized double-blind multicenter | Nasal nafarelin and oral danazol reduced laparoscopically scored endometriosis to a similar degree, with hot flashes and low libido more common on nafarelin and unfavourable cholesterol changes on danazol. 1 |
| Synarel prescribing information | FDA label, adults with endometriosis and children with central precocious puberty | Documents the two approved indications, the bone density warning and the limit on treatment course length. 2 |
Safety
The common side effects are those of low estrogen: hot flashes, vaginal dryness, reduced libido, headaches, mood swings and acne. Nasal irritation is specific to the spray. The main concern with longer use is bone mineral density loss, which is why the label limits the length of an endometriosis course and warns against repeat courses without a specific reason. Nafarelin can cause harm in pregnancy and the label requires that pregnancy be ruled out before starting. 23
There is an initial flare of hormones in the first weeks before suppression sets in, which can temporarily worsen symptoms. In children this can show as a brief increase in pubertal signs. 23
Questions for your clinician
- How long can I safely stay on nafarelin?
- How will my bone density be monitored?
- How does it compare with newer endometriosis options?
Questions people ask
Is nafarelin the same as leuprolide?
They are both GnRH agonists and work the same way, by overstimulating and then shutting down the pituitary's response to GnRH. The practical difference is the route: nafarelin is a nasal spray, leuprolide is an injection. Both are approved for endometriosis and central precocious puberty. 2
Why does nafarelin cause hot flashes?
Because it lowers estrogen to postmenopausal levels. The hot flashes, vaginal dryness and mood changes are the same symptoms many women experience at menopause, and they are expected effects of the drug doing its job. 13
Can nafarelin be used long term?
The label limits the length of an endometriosis course because bone density falls while estrogen is suppressed and does not always fully recover. For precocious puberty, treatment continues under specialist monitoring until the appropriate age for puberty. 23
Is nafarelin sold as a research peptide?
Not in any meaningful way. It is a prescription drug with a specific delivery device, and its uses are narrow. The peptide wellness market has shown little interest in it. 2
Citations
- Henzl 1988, N Engl J Med: nasal nafarelin compared with oral danazol for endometriosis pubmed.ncbi.nlm.nih.gov
- Pfizer: Synarel (nafarelin) prescribing information pfizermedical.com
- Pfizer: Synarel adverse reactions pfizermedical.com