Nafarelin: how it works, what it is used for and side effects

What is nafarelin?

Nafarelin, usually given as nafarelin acetate under the brand name Synarel, is a synthetic analog of gonadotropin-releasing hormone made of ten amino acids. That hormone is known for short as GnRH or LHRH. Unlike many other drugs in its class, nafarelin is absorbed through the lining of the nose rather than injected. This makes it easier to use, although, according to the source article, a stuffy nose or decongestant nasal sprays can reduce how much is absorbed. The drug was developed under the code RS-94991 and approved in the United States in 1990.

How does nafarelin work?

Nafarelin binds to GnRH receptors in the pituitary gland and at first stimulates the gland. With repeated doses, however, the signal becomes continuous instead of arriving in pulses. The receptors are downregulated and become less responsive. As a result, the pituitary releases less luteinizing hormone and follicle-stimulating hormone. In women, the ovaries then produce less estrogen. The result is a temporary low-estrogen state similar to the one after menopause. Source Source Source

This drop in estrogen explains the effect in endometriosis: estrogen-dependent lesions shrink, and the pain linked to them eases during treatment. In central precocious puberty, a higher dose spread across the day suppresses the premature hormone signal and slows early sexual development. In a multicenter double-blind trial, intranasal nafarelin reduced the extent of endometriosis, as assessed by laparoscopy, about as much as oral danazol 1. Most patients improved, without the unfavorable effects on blood lipids seen with danazol. Because estrogen deficiency reduces bone density, endometriosis treatment is generally limited to about six months.

Is nafarelin FDA approved?

Yes. The FDA approved nafarelin for endometriosis in 1990 2. Central precocious puberty was added as an indication shortly afterward. It is supplied as a metered-dose nasal spray delivering 200 micrograms per spray.

What is nafarelin prescribed for?

Nafarelin is used in endometriosis to relieve pain and shrink lesions, and in central precocious puberty in children. It is contraindicated in pregnancy. Nasal decongestants can reduce absorption, so patients are usually advised not to use them close in time to a dose.

What side effects have been described?

According to the prescribing information 3, common side effects are related to estrogen deficiency and to the nasal route:

• Hot flashes and sweating.

• Vaginal dryness and reduced libido.

• Headache.

• Irritation or inflammation of the nasal lining.

• Acne and mood swings. Source

More serious risks and warnings include:

• Loss of bone density, which limits how long endometriosis can be treated.

• Risks to the unborn child; for this reason nafarelin must not be used during pregnancy.

• Changes in mood and behavior, such as irritability, crying and depression. Source

• Seizures.

• Raised pressure inside the skull, also called pseudotumor cerebri, in children.

References provided in the source article

Sources: FDA prescribing information for Synarel; the nafarelin-versus-danazol endometriosis trial (Henzl et al., New England Journal of Medicine, 1988, DOI: 10.1056/NEJM198802253180805 1 ), indexed on PubMed.

Provenance and editorial review status

Adapted for Nutrient Desk from the source article. The claims and source attributions in the original text still require clinical review. This draft has not been cleared for indexing.