From the Guidelines
Gonadotropin-Releasing Hormone Agonists (GnRHa) are associated with significant side effects, including hot flashes, night sweats, mood changes, decreased libido, vaginal dryness in women, and erectile dysfunction in men, as well as more serious effects such as bone density loss (osteoporosis) and increased cardiovascular risk, as reported in a study published in 2019 1. The most frequent side effects of GnRHa include:
- Hot flashes
- Night sweats
- Mood changes
- Decreased libido
- Vaginal dryness in women
- Erectile dysfunction in men These medications can also cause:
- Headaches
- Muscle and joint pain
- Injection site reactions when administered as shots Long-term use may lead to more serious effects such as:
- Bone density loss (osteoporosis)
- Increased cardiovascular risk
- Changes in cholesterol levels Weight gain, fatigue, memory problems, and sleep disturbances are also reported by many patients. In children and adolescents treated with GnRHa for precocious puberty, these effects are generally reversible after treatment ends. The side effects occur because GnRHa initially stimulates but then suppresses sex hormone production, creating a hypogonadal state similar to menopause in women or androgen deprivation in men. Patients starting GnRHa therapy should be monitored for these effects, and in some cases, additional medications may be prescribed to manage specific side effects, particularly bone density loss which may require calcium and vitamin D supplementation or bisphosphonates in long-term therapy, as recommended by a study published in 2009 1. A more recent study published in 2019 1 also highlights the importance of monitoring and managing bone health in patients receiving GnRHa therapy. Overall, the side effects of GnRHa can have a significant impact on a patient's quality of life, and it is essential to carefully weigh the benefits and risks of treatment and to monitor patients closely for any adverse effects.
From the FDA Drug Label
ADVERSE REACTIONS Clinical Trials In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain In a comparative trial of leuprolide acetate injection versus DES, in 5% or more of the patients receiving either drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. *Decreased testicular size 7 11 *Gynecomastia/breast tenderness or pain 7 63 *Hot flashes 55 12 *Impotence 4 12 Cardiovascular System—Angina, Cardiac arrhythmias, Myocardial infarction, Pulmonary emboli. Gastrointestinal System—Diarrhea, Dysphagia, Gastrointestinal bleeding, Gastrointestinal disturbance, Peptic ulcer, Rectal polyps. Endocrine System—Libido decrease, Thyroid enlargement Musculoskeletal System—Joint pain. Central/Peripheral Nervous System—Anxiety, Blurred vision, Lethargy, Memory disorder, Mood swings, Nervousness, Numbness, Paresthesia, Peripheral neuropathy, Syncope/blackouts, Taste disorders.
The side effects of GnRHa (Gonadotropin-Releasing Hormone Agonists) include:
- Cardiovascular:
- High blood pressure
- ECG changes/ischemia
- Congestive heart failure
- Angina
- Cardiac arrhythmias
- Myocardial infarction
- Pulmonary emboli
- Gastrointestinal:
- Anorexia
- Constipation
- Nausea/vomiting
- Diarrhea
- Dysphagia
- Gastrointestinal bleeding
- Endocrine:
- Decreased testicular size
- Gynecomastia/breast tenderness or pain
- Hot flashes
- Impotence
- Libido decrease
- Musculoskeletal:
- Bone pain
- Myalgia
- Joint pain
- Central/Peripheral Nervous System:
- Dizziness/lightheadedness
- General pain
- Headache
- Insomnia/sleep disorders
- Anxiety
- Blurred vision
- Lethargy
- Memory disorder
- Mood swings
- Nervousness
- Numbness
- Paresthesia
- Peripheral neuropathy
- Syncope/blackouts
- Taste disorders
- Respiratory:
- Dyspnea
- Sinus congestion
- Integumentary:
- Dermatitis
- Urogenital:
- Frequency/urgency
- Hematuria
- Urinary tract infection
- Miscellaneous:
- Asthenia
- Depression
- Diabetes
- Fatigue
- Fever/chills
- Hypoglycemia
- Increased BUN
- Increased calcium
- Increased creatinine
- Infection/inflammation
- Ophthalmologic disorders
- Swelling (temporal bone) 2
From the Research
Side Effects of Gonadotropin-Releasing Hormone Agonists (GnRHa)
The side effects of GnRHa can be significant and varied. Some of the common side effects include:
- Fatigue
- Hot flashes
- Decreased libido
- Decreased quality of life
- Obesity
- Diabetes mellitus
- Coronary artery disease
- Decreased bone mineral density
- Increased risk of fractures 3
Skeletal Effects
Prolonged treatment with GnRHa is known to induce bone loss among patients, particularly those with prostate cancer. This can lead to osteoporosis and an increased risk of fractures 4.
Metabolic Effects
GnRHa treatment has been associated with an increased risk of type 2 diabetes and cardiovascular disease in men with prostate cancer. This is likely due to the castrate testosterone levels caused by the treatment 5.
Side Effects in Endometriosis Treatment
GnRHa is also used to treat endometriosis, and the side effects can be ameliorated by the addition of add-back therapy. Common side effects include hypo-oestrogenic symptoms, and some patients may experience irreversible side effects such as memory loss, insomnia, and hot flashes 6, 7.
Long-Term Effects
Long-term effects of GnRHa treatment can include persistent side effects, such as hot flashes and insomnia, and some patients may experience irreversible side effects. Despite these side effects, many patients find GnRHa treatment to be effective in managing their symptoms 7.