Goserelin

Origin and structure

Goserelin is a modified form of gonadotrophin-releasing hormone (GnRH, also called LHRH or gonadorelin), the ten-amino-acid hormone that the hypothalamus releases in pulses to make the pituitary produce LH and FSH. It was developed at the British company ICI under the code ICI 118630. In 1978 Dutta, Furr and colleagues reported that combining a D-amino acid at position 6 with an aza-glycine at position 10 gave analogues about 100 times as potent as the natural hormone at inducing ovulation in rats. Goserelin is the version with a D-serine carrying a tert-butyl group: pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-Azgly-NH2, formula C59H84N18O14, molar mass about 1269 g/mol.

The peptide on its own is cleared within hours: its half-life in the blood is 2 to 4 hours in people with normal kidney function. Zoladex therefore embeds goserelin acetate in a biodegradable copolymer of lactic and glycolic acid. The one-month implant is a rod 1 mm wide, preloaded in a syringe with a wide needle (16 gauge; 14 gauge for the three-month implant) and placed under the skin of the lower abdominal wall. As the polymer breaks down it releases the peptide over 28 days or 12 weeks; with the one-month implant, blood levels peak at around two weeks.

The first patient data for the three-month implant came from the Netherlands. In 1990 a team led from St Ignatius Hospital in Breda reported that all 38 men with advanced prostate cancer who received the 10.8 mg implant reached castrate testosterone levels within four weeks, and that these lasted for more than 14 weeks.

In the Netherlands the licences for Zoladex-3,6 and Zoladex-10,8 are held by AstraZeneca BV. In the US, Zoladex is distributed by TerSera Therapeutics under licence from AstraZeneca.

How it works

Natural GnRH works because it arrives in pulses. Goserelin binds the same receptor on the pituitary and keeps it switched on, so the effect comes in two phases. First LH and FSH rise, and with them testosterone in men and oestradiol in women. With continued exposure the hormone-producing cells of the pituitary become desensitised, LH and FSH output falls and the testes and ovaries lose their signal. About 21 days after the first implant, testosterone in men is down to the level seen after surgical castration and oestradiol in women to postmenopausal values. Suppression is not perfect in everyone: in the US trials, isolated rises in oestradiol were seen in 10% of women after suppression had been reached.

The effect wears off once treatment stops. According to the US label, oestradiol, LH and FSH return to pretreatment values within 12 weeks of the last implant in all but rare cases; the Dutch product information adds that if a three-month implant is not repeated on time, testosterone stays at castrate levels for up to 16 weeks in most men. Rarely, a woman reaches the menopause during treatment and her periods do not return; it is not known whether goserelin or her own gynaecological condition is the cause.

Each licensed use builds on the shutdown. In prostate cancer it removes the testosterone that hormone-sensitive tumours depend on, in premenopausal breast cancer it removes ovarian oestrogen, in endometriosis and fibroids the low-oestrogen state shrinks lesions and fibroids, and before endometrial ablation it thins the lining of the womb. The initial surge is a drawback in cancer, because it can briefly worsen symptoms. The Dutch product information therefore advises considering an anti-androgen at the start, as the EORTC 22863 trial did with cyproterone acetate in the first month.

Is goserelin approved?

Yes. Goserelin is a prescription medicine in the EU and the US, with indications that differ by country and by implant strength.

In the EU there is no central licence from the EMA: each country authorises its own products. In the Netherlands Zoladex-3,6 has been registered since 3 October 1988 (RVG 12277) and Zoladex-10,8 since 20 October 1995 (RVG 18562), both held by AstraZeneca BV; the product information was last revised in June 2026. The Farmacotherapeutisch Kompas lists Zoladex as the only goserelin product. The 10.8 mg implant is not meant for women; according to the US label, the data are insufficient to show that it reliably suppresses oestradiol.

Research-grade goserelin, the freeze-dried peptide sold for laboratory use, is none of these. It has no marketing authorisation, is not made under a medicines licence, has no slow-release implant, and may not be used in people. The approvals below describe Zoladex only.

• Netherlands, Zoladex-3,6: metastatic prostate cancer where testosterone suppression is wanted; adjuvant hormone therapy with radiotherapy for locally advanced prostate cancer (stage T3-T4); moderate and severe endometriosis; fibroids, but only as treatment before surgery for at most 6 months; thinning the lining of the womb before it is removed; and receptor-positive metastatic breast cancer in pre- and perimenopausal women, together with tamoxifen, when removing the ovaries is not considered suitable. Zoladex-10,8 carries only the two prostate-cancer indications.
• US: Zoladex 3.6 mg was first approved in 1989. Its label covers advanced prostate cancer (palliative treatment), locally confined stage T2b-T4 prostate cancer in combination with flutamide and radiotherapy, endometriosis, thinning of the womb lining before ablation for dysfunctional uterine bleeding, and advanced breast cancer in pre- and perimenopausal women. The 10.8 mg implant, approved in 1996, is for the two prostate-cancer uses only. In September 2025 both US labels added a warning for severe skin reactions.

What the research shows

Goserelin has been studied in people since the 1980s, in randomised trials against surgery, chemotherapy, danazol and placebo, and as the hormone treatment in large radiotherapy trials. The main results:

• Against surgical castration (Urology 1995): 283 men with metastatic prostate cancer were randomised to goserelin or removal of the testicles. Testosterone reached castrate levels by week 4 in both groups, and objective response (82% against 77%), time to treatment failure (median 52 against 53 weeks) and survival (median 119 against 136 weeks) were similar.
• With radiotherapy, EORTC 22863 (Lancet Oncol 2010): 415 men with locally advanced or high-grade prostate cancer received radiotherapy alone or radiotherapy plus three years of goserelin. After ten years, 58.1% were alive with goserelin against 39.8% without (hazard ratio 0.60), and 10.3% against 30.4% had died of prostate cancer; cardiovascular deaths did not differ significantly.
• Short course, RTOG 86-10 (J Clin Oncol 2008): 456 men with bulky tumours received four months of goserelin plus flutamide, starting two months before radiotherapy, or radiotherapy alone. At ten years fewer had died of prostate cancer (23% against 36%) or developed distant metastases (35% against 47%); overall survival (43% against 34%) was not significantly different. The US indication with flutamide rests on a trial of this design in 466 men, in which 16% against 33% had a local recurrence at four years.
• Advanced breast cancer: in SWOG-8692, premenopausal women with hormone-receptor-positive advanced breast cancer were randomised to goserelin or surgical removal of the ovaries; in the interim analysis of 124 women cited on the US label, 22% against 12% responded and median survival was 33.2 against 33.6 months. A meta-analysis led from Rotterdam (J Clin Oncol 2001) pooled four trials of goserelin or buserelin in 506 premenopausal women: adding tamoxifen to the GnRH agonist lowered the risk of death (hazard ratio 0.78) and of progression (0.70).
• Early breast cancer, ZEBRA (J Clin Oncol 2002): 1,640 premenopausal women with node-positive early breast cancer received two years of goserelin or six cycles of CMF chemotherapy. In oestrogen-receptor-positive disease (about 74% of women) disease-free survival was equivalent (hazard ratio 1.01, 95% CI 0.84 to 1.20); in receptor-negative disease goserelin did worse (1.76). Early breast cancer is not a registered use of Zoladex in the Netherlands.
• Protecting the ovaries, POEMS (N Engl J Med 2015): 257 premenopausal women with hormone-receptor-negative early breast cancer had chemotherapy with or without goserelin. Among the 135 with complete data, 8% against 22% had ovarian failure after two years, and pregnancies were more frequent (21% against 11% of 218 evaluable women). Missing data weaken the result, and this use is on neither the Dutch nor the US label.
• Endometriosis (US label): in two six-month trials against danazol, lesions shrank by at least half in 63% and 62% of women on goserelin against 42% and 51% on danazol; 92% and 80% stopped menstruating within 8 weeks, and symptoms had fallen by about 84% on average by the end of treatment.
• Thinning the womb lining (US label): in a placebo-controlled trial in 358 premenopausal women with dysfunctional uterine bleeding, two implants before ablation left a thinner lining (median 1.50 against 3.55 mm), and six months after surgery 40% against 26% had no periods.

Side effects and warnings

Most side effects follow from the low sex hormones. In the US trials against surgical castration, hot flushes were reported by 62% of men on goserelin (53% after removal of the testicles), sexual dysfunction by 21% and reduced erections by 18%; 3% had a reaction at the injection site, while 18% of the operated men had surgical complications. In the trials in endometriosis, women on goserelin reported hot flushes (96%), vaginitis (75%), headache (75%), lower libido (61%), mood swings (60%), depression (54%), sweating (45%) and acne (42%); many of these were also frequent on danazol.

In the first weeks the hormone surge can worsen cancer. In SWOG-8692 tumour flare was reported in 23% of women on goserelin against 4% after removal of the ovaries, and in men a flare can cause bone pain, urinary blockage and spinal cord compression. Longer treatment thins the bones: after six months, 109 women in the US trials had lost on average 4.3% of vertebral bone density, part of which had returned six to twelve months later. After two years of treatment for breast cancer, the Dutch product information gives average losses of 6.2% at the femoral neck and 11.5% in the lumbar spine, partly recovered a year later. In endometriosis, adding oestrogen and progestogen limits bone loss and hot flushes.

In men, androgen deprivation lowers glucose tolerance and can lead to diabetes. The Dutch product information lists heart failure and heart attack as common in men, the US label warns of heart attack, sudden cardiac death and stroke, and both warn of a longer QT interval on the ECG. Depression is a warning on both labels, and the Dutch information notes that it can be severe. Rare but serious events include anaphylaxis, pituitary apoplexy (sudden bleeding or infarction in the pituitary, mostly within two weeks of the first dose and sometimes within the first hour) and injury at the injection site: incorrect placement has damaged blood vessels in the abdominal wall, in very rare cases causing haemorrhagic shock that needed transfusion and surgery, so extra care is advised in people with a low BMI or on full anticoagulation. Since September 2025 the US labels also warn of severe skin reactions (SJS/TEN, DRESS and AGEP); the Dutch product information lists rash but not these. The Dutch product information rules out use in pregnancy and breastfeeding; the US label contraindicates it in pregnancy except in the palliative treatment of advanced breast cancer.

Frequently asked questions

What is Zoladex used for?

Zoladex is the brand name of goserelin. In the Netherlands the one-month implant (Zoladex-3,6) is registered for prostate cancer, metastatic breast cancer in women who have not yet reached the menopause (together with tamoxifen), endometriosis, fibroids before surgery and thinning the womb lining before it is removed; the three-month implant (Zoladex-10,8) for prostate cancer only. In every case the aim is to switch off the production of testosterone or oestrogen.

Is Zoladex chemotherapy?

No. It is a hormone treatment: it works by lowering testosterone or oestrogen, not by killing dividing cells. In the ZEBRA trial in premenopausal women with oestrogen-receptor-positive early breast cancer, two years of goserelin prevented recurrence as well as six cycles of CMF chemotherapy; nausea, hair loss and infections were more common with CMF, hormone-related effects at first more common with goserelin. In receptor-negative disease goserelin did worse than chemotherapy.

How long does a Zoladex implant work?

Zoladex-3,6 is designed to release goserelin for 28 days and Zoladex-10,8 for 12 weeks. The implant is biodegradable and is not taken out; in the rare case that it has to be removed surgically, it can be located by ultrasound. Testosterone reaches castrate levels about three weeks after the first implant. After the last one, hormone levels usually recover within 12 weeks, according to the US label.

Does Zoladex put you into the menopause?

Temporarily, in effect. In premenopausal women oestradiol falls to postmenopausal levels within about three weeks and periods usually stop, with hot flushes, vaginal dryness and bone loss. After stopping, periods usually return: in the US endometriosis trials within 8 weeks of the end of treatment, and in ZEBRA 22.6% of women on goserelin had no periods at three years, against 76.9% after CMF chemotherapy. Rarely, periods do not come back. Zoladex is not a reliable contraceptive, so non-hormonal contraception is needed during treatment.

Is goserelin banned in sport?

For men, yes, at all times, in and out of competition. The WADA Prohibited List 2026 names goserelin among the GnRH agonist analogues in class S2.2.1, testosterone-stimulating peptides in males. It is not prohibited for women. The Dutch translation of the list by the Dopingautoriteit carries the same text.

Is research-grade goserelin the same as Zoladex?

No. Zoladex is a licensed medicine: a sterile, biodegradable implant with a known dose, made under pharmaceutical rules, that releases goserelin steadily for one or three months. A freeze-dried peptide sold for laboratory use is neither: its identity and purity are what its certificate of analysis says, nothing more, it has no slow-release form, and it may not be used in people.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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