Does Synarel (nafarelin) cause side effects?

Synarel (nafarelin) is a synthetic protein used to manage endometriosis pain and decrease the size of endometrial implants. Synarel is also used to treat central precocious puberty

Synarel blocks the effects of the natural gonadotropin-releasing hormone (GnRH), a hormone that regulates the output of gonadotropins by the pituitary gland. Gonadotropins (follicle-stimulating hormone or FSH and luteinizing hormone or LH) are hormones that cause estrogen production by the ovaries. 

When Synarel is administered continuously to women in their reproductive years, the pituitary output of FSH, LH, and the production of estrogen by the ovaries are suppressed, which causes menstruation to stop, resulting in a temporary (but reversible) state of "menopause." This temporary state of menopause results in shrinkage of the lining of the uterus (the endometrium). 

Endometriosis is a condition in which the cells that normally form the endometrium inside of the uterus are instead found outside of the uterus. These abnormally located cells (called endometrial implants) are most commonly found on the ovaries, Fallopian tubes, outer surfaces of the uterus or intestines, and on the surface lining of the pelvic cavity

Like the normal endometrium, implants respond to the hormones of the menstrual cycle, i.e., they build up during the month, then break down and bleed during menstruation. However, unlike normal endometrium, the implants bleed internally. (Blood from implants cannot exit the body like blood from the uterus can.) 

The internal bleeding, followed by tissue inflammation and subsequent scarring, is believed to be responsible for the symptoms of pain and infertility in women with endometriosis. Synarel has been found to be effective in relieving the pain of endometriosis and shrinking the endometrial implants. FSH and LH also control the onset of puberty in boys and girls. 

Administration of Synarel blocks the puberty-promoting effects of FSH and LH, reducing the development of secondary sexual characteristics (such as pubic hair) and skeletal development in boys and girls with abnormally early puberty (central precocious puberty) due to problems in the brain that result in high levels of FSH and LH. 

Common side effects of Synarel include

Serious side effects of Synarel include a low estrogen state and temporary menopause, which can cause a small amount of bone thinning that may only partially recover after stopping treatment.

Drug interactions of Synarel include nasal decongestant sprays (for example, Afrin), which may interfere with the absorption of Synarel.

If nasal decongestant sprays are needed, they should be used at least 2 hours before or after using Synarel.

Safe use of Synarel in pregnancy has not been established. Synarel should not be used in pregnancy or in women who may become pregnant while receiving the medication because it might harm the fetus. Pregnancy must be excluded before starting treatment with this medication, and a non-hormonal method of contraception should be used during treatment.

Synarel should not be used by breastfeeding mothers because its safety has not been evaluated.

What are the important side effects of Synarel (nafarelin)?

Side effects of nafarelin are mostly related to the low estrogen state. Common side effects include:

Other important side effects include:

  • acne,
  • muscle pain,
  • reduced breast size, and
  • irritation of the tissue inside the nose.

These side effects should disappear after stopping the medication.

The low estrogen state and the temporary menopause induced by nafarelin can cause a small amount of bone thinning, which may only partially recover after stopping treatment. Patients should discuss this possibility with their doctors and alert their doctors to conditions that they may have that could increase the risk of bone thinning.

These conditions include chronic tobacco use, excessive use of alcohol, family history of osteoporosis, and taking other medications that can cause bone thinning (such as anticonvulsants or corticosteroids).

Synarel (nafarelin) side effects list for healthcare professionals

In clinical trials of 155 pediatric patients, 2.6% reported symptoms suggestive of drug sensitivity, such as

In these 155 patients treated for an average of 41 months and as long as 80 months (6.7 years), adverse events most frequently reported ( > 3% of patients) consisted largely of episodes occurring during the first 6 weeks of treatment as a result of the transient stimulatory action of nafarelin upon the pituitary-gonadal axis:

  • acne (10%)
  • transient breast enlargement (8%)
  • vaginal bleeding (8%)
  • emotional lability (6%)
  • transient increase in pubic hair (5%)
  • body odor (4%)
  • seborrhea (3%)

Hot flashes, common in adult women treated for endometriosis, occurred in only 3% of treated children and were transient.

Other adverse events thought to be drug-related, and occurring in > 3% of patients were

Approximately 3% of patients withdrew from clinical trials due to adverse events.

In one male patient with concomitant congenital adrenal hyperplasia, and who had discontinued treatment 8 months previously to resume puberty, adrenal rest tumors were found in the left testis. Relationship to Synarel is unlikely.

Regular examinations of the pituitary gland by magnetic resonance imaging (MRI) or computer assisted tomography (CT) of children during long-term nafarelin therapy as well as during the post-treatment period has occasionally revealed changes in the shape and size of the pituitary gland.

These changes include asymmetry and enlargement of the pituitary gland, and a pituitary microadenoma has been suspected in a few children. The relationship of these findings to Synarel is not known.


Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists.

In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour.

In these cases, pituitary apoplexy has presented a sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Central/peripheral nervous adverse events: Convulsion.

What drugs interact with Synarel (nafarelin)?

No pharmacokinetic-based drug-drug interaction studies have been conducted with Synarel. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only abou t 80% bound to plasma proteins at 4°C, drug interactions would not be expected to occur.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 8/25/2020
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.