Gonadotropin releasing hormone agonists: Uses, common brands, and safety info

Gonadotropin-releasing hormone (GnRH) agonists are medications that affect the production of sex hormones. These medications were first used in the 80s for their ability to reduce sex hormone levels. They work by continuously stimulating GnRH receptors in the pituitary gland, which, over time, leads to reduced follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone production. GnRH agonists are also known as GnRH analogs or luteinizing hormone-releasing hormone (LHRH) agonists, and they are typically used to treat sex hormone-dependent conditions. GnRH agonists can treat endometriosis, uterine fibroids, precocious puberty, infertility, and prostate cancer.

Continue reading to learn more about gonadotropin-releasing hormone agonists, their uses, and their side effects.

Other gonadotropin-releasing hormone agonists

• Lucrin Depot (leuprorelin)

• Decapeptyl (triptorelin)  

• Gonapeptyl (triptorelin)

• Factrel (gonadorelin)

• Suprefact (buserelin)

• Suprecur (buserelin)

• Maprelin (peforelin)

What are gonadotropin-releasing hormone agonists?

GnRH agonists are decapeptides (protein chains containing 10 amino acids) that act as analogs of GnRH. In other words, they are chemically similar to endogenous GnRH, which is naturally produced in the body. GnRH agonist therapy is used to stop the production of the sex hormones, testosterone, and estrogen. GnRH agonist medications may be prescribed in both men and women. 

They are typically used to treat conditions, such as endometriosis and prostate cancer. The development of these conditions is influenced by levels of sex hormones. Women may take a GnRH agonist to reduce symptoms of endometriosis, which can be worsened by high estrogen and progesterone levels. Men with prostate cancer may be prescribed a GnRH agonist as androgen deprivation therapy to reduce prostate cancer symptoms. 

GnRH agonists are available in different forms. They are often administered as subcutaneous or intramuscular injections given daily, monthly, every three months, or every six months. Certain GnRH agonists, such as buserelin and nafarelin, can be given as a nasal spray. The exact dosage and formulation will depend on the condition being treated and the drug prescribed. 

How do gonadotropin-releasing hormone agonists work?

To understand how GnRH agonists work, it’s important to understand the function of GnRH in the body. GnRH is produced in the hypothalamus and stimulates the pituitary gland to create FSH and LH. These hormones then transmit a signal to the gonads to create either estrogen and progesterone, in the ovaries of women, or testosterone, in the testes of men. This is called the hypothalamic–pituitary–gonadal axis (HPG axis). Normally, GnRH is produced in waves or pulses to regulate the synthesis of sex hormones.

GnRH agonists mimic the actions of GnRH. They work by stimulating GnRH receptors in the pituitary gland, which causes the release of gonadotropins LH and FSH. This causes a flare-up effect or an initial surge of LH and FSH. After starting treatment with a GnRH agonist, there is increased estrogen or testosterone production that can temporarily worsen symptoms of sex hormone-dependent conditions. However, instead of stimulating the GnRH receptors in a pulsatile manner, GnRH agonists continuously stimulate these receptors. 

Over time, GnRH agonist therapy causes a desensitization of the GnRH receptors and ultimately turns off sex hormone production. Continuous administration of this medicine is followed by a drop in FSH and LH hormone secretion caused by the non-pulsatile concentration of GnRH. GnRHa can suppress gonadotropin release and lower sex hormone levels by around 95%. This action is useful for treating sex hormone-dependent conditions and diseases. 

Antigonadotropins, such as progestogens, may be used to prevent the flare-up effect of GnRH agonists at the start of therapy.

What are gonadotropin-releasing hormone agonists used for?  

Gonadotropin-releasing hormone agonists have FDA approved and off-label indications. They are typically used in the treatment of:

• Endometriosis

• Uterine fibroids

• Uterine leiomyomata

• Abnormal menstrual bleeding

• Premenstrual syndrome

• Infertility 

• Breast cancer

• Prostate cancer

• Precocious puberty

GnRH agonists are used to treat conditions that are influenced by levels of sex hormones. GnRH agonists are also used for gender dysphoria, infertility, ovulation induction, and menstrual cycle abnormalities, such as heavy menstrual bleeding. GnRH agonists may be used in combination with other drugs to treat these conditions. 

Who can take gonadotropin-releasing hormone agonists?

Women

Gonadotropin-releasing hormone agonists can treat breast cancer in women by blocking estrogen and progesterone production in the ovaries. Additionally, GnRH agonists can be used for infertility, heavy periods, endometriosis, adenomyosis, uterine fibroids, high testosterone levels, and transgender hormone therapy. 

Men

GnRH agonists in men cause the testicles to stop gonadal testosterone production. They can be used as a form of androgen deprivation therapy for advanced prostate cancer. 

Children

GnRH agonist therapy can be used to delay puberty in children with precocious puberty, otherwise known as early puberty. Precocious puberty can cause the bones, muscles, and reproductive system to develop rapidly in certain children under the age of 8 or 9. GnRH agonists are indicated for treating precocious puberty and delaying puberty for gender dysphoric or transgender youths.  

Seniors

GnRH agonists may be used in older adults over the age of 65. Prostate cancer is more common in elderly men than in younger men, and clinical trials have evaluated the use of GnRH agonists in older men with prostate cancer. Older adults may need to be more closely monitored for adverse effects, especially if they have other conditions like cardiovascular disease or diabetes. 

Can you take gonadotropin-releasing hormone agonists while pregnant or breastfeeding?

GnRH agonists are not safe to take during pregnancy as they can cause harm to an unborn baby. GnRH agonists can also be transferred in small amounts through breast milk. Women who are breastfeeding should not use GnRH agonists.

Are gonadotropin-releasing hormone agonists safe?

Gonadotropin-releasing hormone agonists have been used for decades. They are effective treatment options for various diseases affected by sex hormone levels. However, the suppression of sex hormones can cause complications in some individuals. 

Tell your healthcare provider if you have a history of any of the following before taking gonadotropin-releasing hormone agonists:

• Cardiovascular disease

• Heart attack or stroke

• High blood pressure

• High cholesterol

• Smoking

• Kidney disease

• Diabetes

• Asthma

• Sinusitis

• Osteoporosis

• Brain tumors

• Mental illness

• Seizures

In 2010 the FDA stated it is evaluating the risks of GnRH agonist treatment, such as an increased risk of diabetes and cardiovascular disease. The review is still ongoing, and there are no conclusive statements released yet about GnRHa increasing the risk of cardiovascular disease or diabetes. It is recommended that this type of medicine be used for less than a year for uses other than breast cancer. 

Black Box Warnings

There are no black box warnings for gonadotropin-releasing hormone agonists.

Gonadotropin-releasing hormone agonists recalls

There are no current gonadotropin-releasing hormone agonists drug recalls.

Gonadotropin-releasing hormone agonists restrictions

GnRH agonists should not be used in women who are pregnant or breastfeeding. 

GnRH may cause an increased risk of diabetes and cardiovascular disease. People with risk factors for these conditions should be evaluated before starting treatment with a GnRH agonist. 

Other contraindications will depend on the drug prescribed. Certain GnRH agonists, such as Lupron Depot (leuprolide or leuprorelin), should not be used in women with undiagnosed abnormal bleeding in the uterus. 

GnRH agonists may cause a decrease in bone mineral density. To prevent this, your healthcare provider may suggest taking progestin or estrogen. This treatment is known as add-back therapy for reducing the side effects of GnRHa. The bone-thinning effect of this medicine is reversible in young women taking GnRH agonists for less than six months. 

People with a known hypersensitivity or allergy to GnRH agonists should avoid taking these medications. 

Are gonadotropin-releasing hormone agonists controlled substances?

No, gonadotropin-releasing hormone agonists are not controlled substances.

Common gonadotropin-releasing hormone agonists side effects

GnRH agonists can cause side effects related to the suppression of sex hormones, which include:

• Hot flashes

   

• Breast tissue growth in men (gynecomastia)

• Vaginal dryness

• Decreased libido

• Erectile dysfunction

• Headache

• Fatigue

• Fluid retention

• Weight gain

• Constipation, nausea, or vomiting

• Irritation around the injection site

Serious side effects may include:

• Decreased bone mineral density

• Worsened diabetes 

• Heart problems

• Seizures

• Depression

• Allergic reactions

The side effects of GnRH agonists are caused by menopausal-like symptoms that disappear after stopping treatment. Hypogonadism can affect both men and women causing penile atrophy, vaginal atrophy, gynecomastia, fluid retention, erectile dysfunction, and other sex-specific side effects.

Serious side effects may occur with long-term therapy of GnRH agonists. Add-back treatment may be prescribed to people to reduce side effects. Individuals with a history of bone issues, diabetes, and heart problems should be monitored while using GnRH agonists.  

This may not be a complete list of side effects.

How much do gonadotropin-releasing hormone agonists cost?

Gonadotropin-releasing hormone agonists are available in brand-name and generic formulations. Most Medicare and insurance plans will cover the generic versions of GnRH agonists. However, costs will vary depending on the insurance plan. Talk to your pharmacist or insurance company directly to determine the exact cost of your medication through your insurance plan. Without insurance, the price can vary widely depending on the medication and quantity of medication prescribed. Using a prescription discount card from SingleCare may help reduce the cost of gonadotropin-releasing hormone agonists at participating pharmacies.