Nafarelin (Synarel)_Dosage, benefits & legal status
Also known as Synarel, Nasanyl, nafarelin acetate, nafarelin acetate hydrate
GnRH with one mirror-image residue, and the only drug of its class sold in the US as a nasal spray. In a 213-woman trial it shrank endometriosis as much as danazol, without danazol's rise in LDL and fall in HDL cholesterol.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Nafarelin (Synarel)?
Plain language first. The technical label stays, but it never stands alone.Overview
Endometriosis pain is fed by estrogen, and early puberty in children is driven by hormones that switch on years too soon; nafarelin turns both down by quieting the pituitary gland. In a 6-month trial of 213 women, the spray reduced endometriosis as much as danazol tablets, and in the label's data 60% were symptom-free at the end of treatment. In children, the pituitary signal fell to prepubertal levels within a month. The main cost is bone: bone mass on a DEXA scan fell 3.2% over 6 months and was still 1.4% down 6 months later, and the label does not recommend a second course.
Nafarelin is native GnRH (gonadorelin) with 3-(2-naphthyl)-D-alanine in place of glycine 6, a decapeptide that keeps the natural pyroglutamate start and glycinamide end. Given as a 200 mcg metered nasal spray (about 2.8% absorbed), it first stimulates and then, under continuous exposure, desensitizes pituitary GnRH receptors, so sex hormone output falls within about 4 weeks, to prepubertal levels in children. Synarel (NDA 019886, now Pfizer) was approved on February 13, 1990, and is labeled in the US for endometriosis and central precocious puberty; several European countries license it for IVF instead of puberty, and Japan sells it as Nasanyl.
What it's used for
A prescription nasal spray used for 6 months to treat endometriosis, and in children with central precocious puberty until puberty is wanted again. Outside the US it is also used to switch off the pituitary before ovarian stimulation for IVF.
How does Nafarelin (Synarel) work?
What it does in the body, and where.Nafarelin is a long-lasting version of GnRH, the brain hormone that tells the pituitary to drive the ovaries and testes, and steady exposure to it switches that signal off.
- 01Through the noseEach spray is absorbed through the lining of the nose. Only about 2.8% of the dose reaches the blood, peaking 10 to 40 minutes later in women, and the label calls it a potent agonist at pituitary GnRH receptors.
- 02A brief surgeEarly doses act like a strong GnRH pulse: LH and FSH rise and the ovaries or testes briefly make more hormone. In children this flare can bring vaginal bleeding or breast enlargement in the first month.
- 03Switching offWithout the natural on-off rhythm, the receptors desensitize and are downregulated. By about 4 weeks of twice-daily use, sex hormone output has fallen (to prepubertal levels in children), so endometriosis implants shrink, periods stop and puberty pauses. It reverses after stopping: normal cycles returned in 82% of women who were not pregnant by the second month after treatment and in 100% by the third.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Against danazol (endometriosis)
FDA-approved- Human trial213 women, 6 months, double-blind: laparoscopic scores fell in all three groups with no significant differences, and more than 80% in each group had less disease.
- Human trialDanazol raised LDL and lowered HDL cholesterol; nafarelin did not. Nafarelin users more often reported hot flashes and lower libido.
- Human trialAbout 39% of the 149 women who tried to conceive after treatment did so, at similar rates across groups.
Label data on 400 mcg a day
FDA-approved- Human trialNo periods in about 65% at 60 days, 80% at 90 days and 90% at 120 days.
- Human trialAt the end of treatment 60% were symptom-free, 32% mild, 7% moderate and 1% severe; 6 months later, of those symptom-free, 50% still were, 33% had mild and 17% moderate symptoms.
- Human trialOne controlled trial found 400 mcg a day clinically comparable to monthly leuprolide depot 3.75 mg for period pain, pain during sex and pelvic pain; its publication has not been identified.
Bone density
FDA-approved- Human trialOver 6 months, vertebral trabecular density by QCT fell 8.7% and total vertebral bone mass by QCT 4.3%; after treatment they were still 4.9% and 3.3% below baseline. By DPA, total vertebral mass fell 5.9%.
- No dataBy DEXA, bone mass fell 3.2% and was 1.4% below baseline 6 months after stopping; the label says some of the loss may not be reversible.
Central precocious puberty
FDA-approved- Human trialPeak LH after a GnRH challenge fell to prepubertal levels (under 15 mIU/mL) within 1 month, and growth slowed to 5 to 6 cm a year or less in most children within the first year.
- Human trialBreast development stopped or regressed in 82% of girls, genital development in 100% of boys and pubic hair in 54%; suppression reversed in all 69 children followed for a year after treatment.
- No dataThe label does not name the trials or say whether they had a comparison group.
Its US approval is often given only as February 1990; the date is February 13, 1990 (NDA 019886). A 1990 paper (PMID 2137971, Henzl and Kwei in the American Journal of Obstetrics and Gynecology) is often cited as the key clinical study, but it is an endometriosis paper with nothing on puberty; the randomized trial against danazol is NEJM 1988 (213 women). It is often described as used for endometriosis and central precocious puberty; that holds in the US, while the UK, France and the Netherlands license it for endometriosis and IVF and not for puberty, and Japan sells it as Nasanyl for endometriosis and fibroids, with an assisted reproduction indication backed by a 2022 PMDA review. Calling it the only nasal GnRH agonist is accurate for the US market but not worldwide: buserelin is also sold as a nasal spray in Europe (Suprecur). The 8.7% bone loss often quoted is spine trabecular density by QCT, the largest of four measures; by DEXA the loss was 3.2%, with 1.4% remaining 6 months later. The endometriosis dose of 400 mcg a day is two sprays a day in total; two sprays into each nostril twice a day is the puberty dose. The half-life is about 3 hours in women on the US label, against about 4 hours on the UK label. A potency of about 200 times native GnRH is sometimes quoted; the label calls it potent but gives no figure.
The published record
Papers and trials about Nafarelin (Synarel)
235 papers tagged human · 196 not reviews or lab · 84 clinical trial publications
12 registered trials · none with posted results
Furthest stage reached: Approved in the US
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Nafarelin (Synarel)
Evidence
FDA-approved
Category
Sexual and hormonal
Common vial
Varies
Half-life
About 3 hours in women, 2.5 hours in children
How much, and do you cycle it?
The range, and whether you take breaks.400 mcg a day for endometriosis; 1600 mcg a day for early puberty (label), twice daily (three times daily at the highest puberty dose). A single 6-month course for endometriosis; continuous for early puberty FDA label
Endometriosis experience is limited to 6 months, and the label does not recommend retreatment because there are no safety data; bone density should be checked first if it is considered. In children it is used daily until puberty is wanted again.
How long does it stay in the body?
The half-life, and where the figure comes from.About 3 hours in women, 2.5 hours in childrenFDA label
After a spray, blood levels peak in 10 to 40 minutes in women and 10 to 45 minutes in children; on average only 2.8% (1.2 to 5.6%) of a 400 mcg dose is absorbed. About 80% is protein-bound, and it did not build up with twice-daily use for 22 days. Peptidases break it down, not CYP450 enzymes; in men given a radiolabeled dose under the skin, metabolites had a serum half-life of about 85.5 hours and about 3% left unchanged in urine. A stuffy nose did not significantly change absorption. The UK label gives about 4 hours and the Dutch label 2 to 4 hours.
Source: Synarel US prescribing information, clinical pharmacology
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How is it given?
Dosing context and source notes.Supplied as a ready-made solution, so there is nothing to mix.
Label range: 400 up to 1800 mcg per day. Synarel US prescribing information (November 2025), dosage and administration
Sprayed into the nose from a metered pump; each spray gives about 200 mcg of nafarelin in about 100 microliters. Endometriosis: one spray into one nostril in the morning and one into the other nostril in the evening (400 mcg a day), starting between days 2 and 4 of the cycle, for 6 months; if regular periods continue after 2 months, one spray into each nostril morning and evening (800 mcg a day). Central precocious puberty: 2 sprays into each nostril morning and evening (1600 mcg a day), raised to 3 sprays into alternating nostrils three times a day (1800 mcg a day) if suppression is inadequate and the child is taking every dose, with about 30 seconds between sprays. If a topical nasal decongestant is needed, it should be used at least 2 hours after a dose, and sneezing during or just after a dose should be avoided. Effects in kidney or liver impairment have not been determined, so no adjustment is given. Supplied as an 8 mL bottle of ready-made 2 mg/mL solution with at least 60 sprays after priming, about 30 days at the endometriosis dose or about 7 days at the puberty dose, stored upright at 25°C and protected from light. The dose comes in fixed sprays, so there is nothing for the calculator to measure.
How do you store it?
Before mixing, and after.Supplied ready to use. Store it as the label says.
Nafarelin (Synarel) comes as a ready-made solution, prefilled syringe or ampoule, not a powder, so there is no mixing step and no reconstitution clock. Keep it in its original pack and follow the storage and expiry dates on the label. Many ready-made peptide medicines are kept in the fridge and must not be frozen; a few are made to be stored at room temperature.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 30% charged residues, 40% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Allergy to GnRH, GnRH agonist drugs or any ingredient of the spray
- Undiagnosed abnormal vaginal bleeding
- Pregnancy or possible pregnancy (major abnormalities in 4 of 80 rat fetuses at 6.4 mcg/kg a day)
- Breastfeeding
Stop and get help
- A blistering or peeling rash, or a rash with fever (possible severe skin reaction)
- Severe headache or changes in vision (possible raised pressure inside the skull)
- A seizure, or new or worsening depression or thoughts of suicide
Common effects
- Nasal irritation in about 10% of women treated for endometriosis
- Hot flashes and lower libido were reported more often than with danazol in the 213-woman trial; the label also lists vaginal dryness, headache, mood swings, insomnia, acne, muscle aches, smaller breasts and swelling
- In 155 children treated for a mean of about 41 months: acne 10%, temporary breast enlargement 8%, vaginal bleeding 8%, mood swings 6%, a temporary rise in pubic hair 5% and rhinitis 5%; about 3% stopped for side effects
- Total cholesterol rose from 191.8 to 204.5 mg/dL on nafarelin and from 193.1 to 207.7 mg/dL on danazol, but HDL fell below 30 mg/dL in 0% against 43%, and LDL rose above 190 mg/dL in 0% against 15%
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Nafarelin (Synarel) approved?
And where the numbers on this page come from.Yes. Nafarelin (Synarel) is FDA approved and available on prescription in the United States. It is also approved in the Netherlands, the United Kingdom, France, Canada, and Japan.
- Approval statusFDA-approved
- RouteSprayed into the nose
- Checked21 October 2026
- Approved outside the USNetherlands, United Kingdom, France, Canada, Japan: Netherlands since October 14, 1991 (endometriosis, fibroids before surgery, IVF); the UK under its current license since August 13, 2003 (endometriosis, IVF); France (endometriosis, IVF); Canada (marketed by Pfizer Canada); and Japan as Nasanyl (endometriosis January 1995, fibroids March 1999). Pfizer Japan has stated it is also approved for IVF in Germany and Australia. The UK, France and the Netherlands do not license it for precocious puberty.This does not change the United States position above.
- DoseFrom the drug label. The manufacturer tested this range and a regulator reviewed it.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesDrugs@FDA, NDA 019886 (Synarel)Synarel US prescribing information (S-040, November 2025)FDA approval letter, NDA 019886/S-013 (December 24, 1998)DailyMed, SynarelFDA GSRS substance records, nafarelin (UNII 1X0094V6JV) and nafarelin acetate (UNII 8ENZ0QJW4H)KEGG D00990, nafarelin acetateHenzl MR et al., New England Journal of Medicine 1988;318:485-489Henzl MR, Kwei L, American Journal of Obstetrics and Gynecology 1990;162:570-574Synarel UK summary of product characteristics (emc)Synarel Dutch summary of product characteristics (CBG)PMDA review report, Nasanyl (2022)ANSM, Synarel availabilityHealth Canada shortage report 197652AHFS monograph, nafarelin (drugs.com)
What has happened recently
The FDA approved Synarel (NDA 019886) on February 13, 1990, as a new molecular entity under standard review. Its US labeling covers endometriosis and central precocious puberty under the same NDA; the date the puberty indication was added is not established, and AHFS describes it as an FDA-designated orphan drug for that use. A supplement approved on December 24, 1998, addressed to Searle as the holder, added a controlled trial showing 400 mcg a day was clinically comparable to monthly leuprolide depot 3.75 mg, plus DEXA bone data. Pfizer holds the NDA now, and there is no generic; the label, last revised in November 2025 (a Medication Guide supplement approved November 24, 2025), carries warnings for psychiatric events, seizures, raised pressure inside the skull and severe skin reactions. It has no US approval for IVF. The Netherlands authorized it on October 14, 1991 (endometriosis, fibroids before surgery, IVF); the current UK license dates from August 13, 2003 (endometriosis and IVF, with no puberty indication); France licenses it for endometriosis and IVF; Pfizer Canada markets it; and Japan approved it as Nasanyl for endometriosis in January 1995 and fibroids in March 1999, with an assisted reproduction indication reviewed in 2022. Supply was disrupted in Canada from October 27, 2023, to January 10, 2024, and in France in 2026 until July 17, 2026.
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What else is like Nafarelin (Synarel)?
Others in Sexual and hormonal, side by side.If you're weighing Nafarelin (Synarel), it's worth reading Octreotide (Sandostatin), Pasireotide (Signifor), and PT-142 in the same class.
GnRH with one mirror-image residue, and the only drug of its class sold in the US as a nasal spray. In a 213-woman trial it shrank endometriosis as much as danazol, without danazol's rise in LDL and fall in HDL cholesterol.
- Dose
- 400 mcg a day for endometriosis; 1600 mcg a day for early puberty (label)
- How often
- Twice daily (three times daily at the highest puberty dose)
An approved hormone blocker since 1988: it lowers growth hormone instead of raising it.
- Dose
- 50 to 500 mcg three times daily, or a 10 to 40 mg monthly depot (label)
- How often
- Two to four times daily, or every 4 weeks (depot)
A ring-shaped six-residue drug for Cushing's disease and acromegaly, traded for a high rate of diabetes.
- Dose
- 0.3 to 0.9 mg twice daily, or 10 to 60 mg monthly LAR (label)
- How often
- Twice daily (Signifor) or every 28 days (Signifor LAR)
A Palatin-style code number with no published compound behind it.
- Dose
- Research only
- How often
- Not established
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
Sources
- Drugs@FDA, NDA 019886 (Synarel)(2026)Approved February 13, 1990, as a new molecular entity; prescription status, Pfizer; supplements through S-40 (November 24, 2025).
- Synarel US prescribing information (S-040, November 2025)(2025)Chemical name; doses for both indications; half-life about 3 hours in women and 2.5 in children; bone loss; adverse reactions in 155 children; lipid data against danazol.
- FDA approval letter, NDA 019886/S-013 (December 24, 1998)(1998)Addressed to Searle; added a trial finding 400 mcg a day clinically comparable to leuprolide depot 3.75 mg monthly, and DEXA bone data.
- DailyMed, Synarel(2026)The only nafarelin label listed, with no generic; NDC 0025-0166-08; drug-sensitivity symptoms in 3 of 1,509 healthy adult trial participants.
- FDA GSRS substance records, nafarelin (UNII 1X0094V6JV) and nafarelin acetate (UNII 8ENZ0QJW4H)(2026)C66H83N17O13, MW 1322.47; alternate name LHRH, 6(D-NAL(2)), confirming position 6 as the only change.
- KEGG D00990, nafarelin acetate(2026)CAS 86220-42-0; ATC H01CA02; Japanese name nafarelin acetate hydrate.
- Henzl MR et al., New England Journal of Medicine 1988;318:485-489(1988)213 women randomized for 6 months to nafarelin 400 or 800 mcg a day or danazol 800 mg a day: similar falls in laparoscopic scores; about 39% of 149 trying to conceive did so.
- Henzl MR, Kwei L, American Journal of Obstetrics and Gynecology 1990;162:570-574(1990)An endometriosis paper (PMID 2137971), not the randomized trial against danazol; no abstract available.
- Synarel UK summary of product characteristics (emc)(2022)PL 00057/1052, first authorization or renewal dated August 13, 2003; endometriosis and IVF indications, no puberty indication; half-life about 4 hours.
- Synarel Dutch summary of product characteristics (CBG)(2022)RVG 15086, first authorized October 14, 1991; endometriosis, fibroids before surgery and pituitary down-regulation for IVF.
- PMDA review report, Nasanyl (2022)(2022)Japan approvals for endometriosis in January 1995 and uterine fibroids in March 1999; assisted reproduction indication reviewed July 14, 2022.
- ANSM, Synarel availability(2026)Supply disrupted in France in 2026; normal supply restored July 17, 2026.
- Health Canada shortage report 197652(2024)Shortage from October 27, 2023, to January 10, 2024, after a manufacturing disruption.
- AHFS monograph, nafarelin (drugs.com)(2026)Describes nafarelin as an FDA-designated orphan drug for central precocious puberty.
Beyond these, 294 records are indexed. Browse the records