Goserelin (Zoladex): how hormone suppression works

What is goserelin?

Goserelin acetate, sold as Zoladex, is a synthetic ten-amino-acid analogue of gonadotropin-releasing hormone, abbreviated GnRH or LHRH. GnRH is produced in the hypothalamus and stimulates the pituitary gland to release luteinizing hormone and follicle-stimulating hormone. These in turn stimulate the testes and ovaries. Goserelin acts more strongly and for longer than the natural signal. A small, waxy solid implant is placed under the skin of the abdomen and slowly releases the medicine. Goserelin was developed under the code ICI-118630 and received US approval in 1989. Source Source

How does goserelin work?

Goserelin binds to GnRH receptors in the pituitary gland. Initially, it briefly stimulates hormone release: luteinizing hormone and sex hormones rise temporarily. This effect is called a “flare.” The implant then acts continuously rather than in natural pulses. The receptors become less sensitive and decrease in number. Within a few weeks, luteinizing hormone and follicle-stimulating hormone fall. Testosterone reaches castrate levels in men, while estrogen falls to postmenopausal levels in women.

Lowering hormones serves different purposes depending on the disease. In prostate cancer, it deprives hormone-sensitive tumor cells of testosterone. In premenopausal estrogen-receptor-positive breast cancer, it reduces the growth signal from the ovaries. In endometriosis, it creates a temporary low-estrogen state. The table sets out these relationships.

In the long-term ZEBRA trial, goserelin was equivalent to standard CMF chemotherapy in disease-free and overall survival 1. The trial involved premenopausal women with early estrogen-receptor-positive breast cancer and involved lymph nodes. It avoided the acute toxicity of chemotherapy.

Is goserelin FDA-approved?

The FDA approved goserelin in 1989 2. It was developed by ICI Pharmaceuticals, later Zeneca and now AstraZeneca. The implant is available at 3.6 mg for monthly administration and 10.8 mg for administration every three months. Its approved uses in oncology and gynecology have expanded over time.

What is goserelin prescribed for?

The source article lists the following uses:

• Advanced prostate cancer, alone or alongside radiation therapy or an antiandrogen

• Advanced breast cancer in premenopausal and perimenopausal women

• Endometriosis

• Thinning the uterine lining before surgical ablation for heavy uterine bleeding

Because of its hormonal effects, goserelin is contraindicated during pregnancy.

What side effects are possible?

Many common side effects result from low sex hormone levels. The prescribing information 2 lists effects including:

• Hot flashes and sweating

• Sexual dysfunction and vaginal dryness

• Headaches

• Reactions at the implantation site

• Loss of bone density with prolonged use

Other important risks include:

• A temporary worsening of prostate cancer due to the initial flare; an antiandrogen may be used to counter this when needed.

• An increased risk of hyperglycemia and cardiovascular events with long-term androgen deprivation

• Rare pituitary apoplexy, an acute injury to the pituitary gland caused by bleeding or impaired blood supply

Studies at a glance

Condition	Hormone level reduced	Treatment aim
Prostate cancer	Testosterone	Deprive hormone-sensitive tumor cells of a growth signal
Breast cancer before menopause	Estrogen from the ovaries	Estrogen-receptor-positive tumors can grow in response to this hormone
Endometriosis	Estrogen, temporarily	A low-estrogen state can shrink endometriosis lesions

References provided in the source article

Sources: FDA prescribing information for Zoladex; the ZEBRA trial (Kaufmann et al., European Journal of Cancer, 2003, DOI: 10.1016/s0959-8049(03)00392-7 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.