Leuprorelin (leuprolide)

A synthetic nine-amino-acid version of GnRH, the hormone that controls the pituitary gland's release of the two hormones that drive the sex glands. The US label's chemical name shows a modified glutamate at one end, a mirror-image leucine at position 6 and a modified tail, which is why it cannot be written in one-letter code.

Sold as

Long-acting depot injection under the skin or into muscle, given every one to six months.

Legal status in the EU

An approved prescription medicine in the EU, both EU-wide (Camcevi, 2022) and through national approvals of several depot formulations. Banned in sport under the 2026 WADA list, section S2.2.1 on testosterone-stimulating peptides, which lists GnRH and its agonist analogues including leuprorelin — the ban applies to men only.

Released in pulses, GnRH stimulates the pituitary; but constant exposure shuts the receptor down. So after an initial rise, the signalling hormones fall, and with them testosterone or oestrogen, down to the levels seen after castration. That first phase causes a temporary flare; the US label reports a transient testosterone rise of around 50 per cent above baseline.

Part of the bodyWhat happensHow it is knownKind of evidence

The hormone switch in the brain

A small gland under the brain, the pituitary, tells the testicles or the ovaries what to do. Leuprorelin is a copy of the natural signal that switches that gland on. For the first few days the signal gets louder, and testosterone rises by about half again above where it started. Held on constantly instead of arriving in pulses, the switch then jams shut. Within three to four weeks testosterone falls below 50 ng/dL — nanograms per decilitre, the usual way blood testosterone is counted. That is the level seen in a man whose testicles have been removed, and it holds for as long as the injections continue.

Measured in 137 men given the six-monthly injection and followed for 336 days, and in 144 men given the three-monthly injection over 24 weeks. The size of the initial rise is stated in the US Lupron Depot label.

Measured in people

Source [01]Source [05]Source [06]

Testicles, sex drive and erections, in men

With testosterone gone, the testicles shrink and usually stay small while treatment continues. Sex drive typically goes with it, and erections often stop. The EU product information lists shrunken testicles, erectile difficulty, breast tenderness, breast growth and infertility as common effects. Common here means more than 1 in 100 men and fewer than 1 in 10. In the two American trials of the three-monthly 22.5 mg injection, shrinking testicles were recorded in 19 of 94 men, or 20.2%.

Recorded in 94 men on the three-monthly dose in the trials behind the US label, and pooled across the leuprorelin trials summarised in the EU product information.

Measured in people

Source [01]Source [05]

Periods, the womb and the ovaries, in women

Oestrogen falls to the level of the menopause and periods stop. In the endometriosis studies, 74% of women had no period after one month of the monthly injection and 98% after two. In women with fibroids and heavy bleeding, the womb and the fibroids shrink and the blood count recovers. Periods come back after stopping, but not straight away: 7% of women had a normal cycle in the first month off treatment, 71% in the second and 95% in the third.

Measured in 166 women with endometriosis and in the fibroid trials behind the US Lupron Depot 3.75 mg label, over three to six months of treatment. Also measured in a trial of 52 women, put by chance into either the drug group or a dummy-injection group.

Measured in people

Source [07]Source [08]

Growth and puberty, in children

In a child whose puberty has started years too early, the signs of puberty stop and the growth spurt slows down. Height gain fell from 10.6 cm a year before treatment to about 5 to 6 cm a year over the first 72 weeks, and about 4 to 4.5 cm a year after that. Bone maturity, which had been running about three years ahead of the child's actual age, stopped running ahead. The point of slowing all this down is that the growth plates close later, so there is more time left to grow.

Measured in 55 children treated for a mean of 3.9 years and followed for a mean of 3.5 years afterwards, and in 45 children given the six-monthly injection for 144 weeks.

Measured in people

Source [09]Source [10]Source [11]

Bones

Sex hormones are what keeps bone being rebuilt, so taking them away thins it. In the 30 men who were starting treatment, bone fell by 2.5% at the hip and 4.0% at the spine over twelve months. The study's authors put that at five to ten times the loss seen in healthy men of the same age and in men with the same cancer who were not on treatment. Women on the endometriosis dose lost 3.2% at the lower spine in 24 weeks and 6.3% by 52 weeks. Taking a norethindrone acetate tablet alongside — a hormone tablet given to protect bone — cut that to 0.3% and 1.0%. Pooling 16 studies of 519,168 men, fractures were about 39% more likely on this class of drug (odds ratio 1.39, 95% confidence interval 1.26 to 1.52).

Measured over 12 months in 30 men who were starting treatment, inside a study of 152 men with prostate cancer and 43 men of the same age without it. Also from the women's trials behind the US label, and pooled across 16 cohort studies of 519,168 men.

Measured in people

Source [07]Source [12]Source [13]

Blood sugar, body fat and the heart

Fat goes up and muscle goes down. The 30 men starting treatment gained 10.4% total body fat and lost 3.5% lean mass over twelve months. Blood sugar drifts up, and the product information tells doctors to check it, because new diabetes and worsening of existing diabetes are both reported. One large trial put leuprorelin head to head with another drug doing the same job. Over 48 weeks, serious heart events happened to 6.2% of the men on leuprorelin and 2.9% of those on the comparison tablet. Serious heart event here means heart attack, stroke, or death from a heart cause.

Body fat measured over 12 months in 30 men starting treatment. Diabetes and heart disease tracked through insurance records in 73,196 American men aged 66 and over. The head-to-head heart figures come from 930 men put into groups by chance and followed for 48 weeks.

Measured in people

Source [12]Source [14]Source [15]

Lupron (NDA 019010) was approved by the FDA on 9 April 1985 for the palliative treatment of advanced prostate cancer. In the EU it is also approved for endometriosis, fibroids and early puberty. The study behind the EU approval of Camcevi included 137 men: four weeks after the first injection, 98.5 per cent (135 of 137) had fallen to castration-level testosterone, and 97 per cent (133 of 137) stayed below that level throughout the 48-week period. Camcevi was approved in the EU on 24 May 2022.

Days 1 to 7: testosterone goes up, by about half again above where it started, and symptoms can briefly get worse. Weeks 3 to 4: testosterone drops below 50 ng/dL and stays there. On the three-monthly injection, 141 of 143 men — 98.6% — were below it by day 28. Month 1 to 2 in women: periods stop in 74% after one month and 98% after two. Month 3 onwards: hot flushes, tiredness and loss of sex drive are established, and bone density starts falling measurably within the first year. After the last injection, recovery is slow and uneven. Ninety days after stopping, mean testosterone in the 184 men measured was still 58.6 ng/dL, below the castration threshold. In women, normal periods had returned in 7% after one month, 71% after two and 95% after three.

What was measuredWhat happenedIn whomHow it is known

Keeping testosterone at the castration level for a year

88.8% of the men on leuprorelin stayed below 50 ng/dL through week 48, against 96.7% of the men on the comparison tablet relugolix.

930 men with advanced prostate cancer: 308 had leuprorelin and 622 had the tablet, everyone knew which, 48 weeks

Measured in people

Source [14]

How fast testosterone falls in the first days

By day 4, none of the men on leuprorelin had reached the castration level; 56.0% of the men on the comparison tablet had.

The same 930 men, measured on day 4

Measured in people

Source [14]

How much testosterone had come back 90 days after stopping

Mean testosterone was 58.6 ng/dL after leuprorelin — still below the castration threshold — against 288.4 ng/dL after the comparison tablet.

184 of the 930 men, measured once, 90 days after the last treatment

Measured in people

Source [14]

Serious heart events (heart attack, stroke, death from a heart cause)

6.2% of the men on leuprorelin, against 2.9% on the comparison tablet. The trial reports a hazard ratio of 0.46 in favour of the tablet, meaning events came at less than half the rate. The range the true figure most likely sits in runs from 0.24 to 0.88.

930 men with advanced prostate cancer, 48 weeks

Measured in people

Source [14]

Testosterone suppression on the six-monthly injection

97.0% of men stayed below 50 ng/dL from day 28 through day 336, with a likely range of 92.2% to 98.9%. There was no comparison group — every man in the study received the drug.

137 men with advanced prostate cancer, single arm, 336 days

Measured in people

Source [02]Source [06]

PSA, the blood marker used to follow prostate cancer

Mean PSA fell from 35.9 ng/mL at the start to 1.2 ng/mL by day 168. Again there was no comparison group, and the product information states that tumour size itself was not measured.

132 men on the three-monthly 21 mg injection, 24 weeks

Measured in people

Source [05]

Blood count in women with anaemia caused by fibroids

By week 12, 75% of the women given leuprorelin together with iron had reached a haematocrit of at least 36% and a haemoglobin of at least 12 g/dL. On iron alone, 49% did. Haemoglobin is the protein that carries oxygen; haematocrit is the share of the blood made up of red cells.

104 women on leuprorelin plus iron and 98 women on iron alone, entering with a haematocrit of 30% or less and/or a haemoglobin of 10.2 g/dL or less, 12 weeks

Measured in people

Source [07]

Bone at the lower spine, with and without an add-back tablet

−3.2% at 24 weeks and −6.3% at 52 weeks on leuprorelin alone, against −0.3% and −1.0% when norethindrone acetate 5 mg daily was taken alongside it.

Women treated for endometriosis in a controlled study: 41 on leuprorelin alone and 42 on both at 24 weeks, 29 and 32 at 52 weeks

Measured in people

Source [07]

New diabetes

New diabetes came at about 1.44 times the rate seen in men with the same cancer who were not on this class of drug. This came from insurance records, not from a trial that assigned anyone by chance, so it shows an association rather than proving cause.

73,196 American men aged 66 and over, diagnosed 1992–1999, followed to 2001

Measured in people

Source [15]

Depression

The odds of depression were about 46% higher in men on hormone-blocking treatment than in the comparison groups (odds ratio 1.46, likely range 1.28 to 1.67). Pooled across the treated men, about 210 in every 1,000 were recorded as depressed.

38 studies, 360,650 people, database search run to August 2023

Measured in people

Source [16]

Adult height in girls treated for puberty that started far too early

Mean adult height 162.5 cm, which was 4.0 cm more than the height predicted for those same girls before treatment started. The comparison is each girl's own prediction, not a group of untreated children.

30 girls with adult height data, measured at a mean age of 21.8 years

Measured in people

Source [09]

Dementia

Pooled across cohort studies, dementia came at about 1.21 times the rate in men who had this class of treatment (likely range 1.13 to 1.30). The authors write that the studies they searched had shown conflicting results, and that whether the treatment causes dementia or is merely associated with it still needs to be worked out.

11 cohort studies, 339,400 cases and 436,851 controls

Studies in people disagree

Source [17]

Period pain and pelvic pain in endometriosis

Period pain, pelvic pain and pelvic tenderness all improved significantly more than on a dummy injection. Periods stopped in every woman given the drug and oestrogen fell to menopausal levels.

52 women with endometriosis, assigned by chance, with neither they nor their doctors told which they had

One small study

Source [08]

Hot flushes and sweating are the most common effects. The initial testosterone rise can briefly make the disease worse, with bone pain and, at worst, pressure on the spinal cord. The product information warns about high blood sugar, new-onset diabetes and blood fat disturbances; an increased risk of heart attack, sudden cardiac death and stroke; and serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Long-term hormone suppression lowers bone density.

EffectWhat it feels likeHow often

The disease briefly getting worse after the first injectionSerious

In the first week testosterone goes up before it goes down. In men with prostate cancer this can mean new or worse bone pain, blood in the urine, difficulty passing urine, or a blocked tube from the kidney. At worst the cancer presses on the spinal cord, which can cause weakness or paralysis. The product information says an anti-androgen tablet, started three days before and continued for the first two to three weeks, has been reported to prevent this. The symptoms usually settle as treatment continues.

Not reported as a percentage. The labels describe it as an expected consequence of the first injection, when testosterone rises by about 50% above where it started.

Source [01]Source [05]

Heart attack, stroke and sudden death from a heart causeSerious

The EU product information lists heart attack as an uncommon reaction, meaning between 1 in 1,000 and 1 in 100. It warns separately that this class of drug has been linked to a raised risk of heart attack, sudden cardiac death and stroke in men. It can also lengthen the heart's electrical recovery time, which matters for anyone already on medicines that do the same.

6.2% of the 308 men on leuprorelin over 48 weeks in the one head-to-head trial, against 2.9% of the 622 men on the comparison tablet.

Source [05]Source [14]

Broken bones from thinned boneSerious

Bone loss starts in the first year and is fastest then. It is the reason the endometriosis course is capped at six months on its own, or twelve months in total when a norethindrone acetate tablet is taken alongside to protect bone.

Fractures were about 39% more likely than in men not on this class of drug (odds ratio 1.39), pooled across 16 studies of 519,168 men. The EU product information reports fractures from thinned bone in 5% of patients after 22 months of treatment and 4% after five to ten years.

Source [05]Source [07]Source [13]

Severe skin reactions that strip the skinSerious

Stevens-Johnson syndrome and toxic epidermal necrolysis are reactions in which the skin blisters and peels. They can be life-threatening or fatal. Both labels tell prescribers to warn patients about the signs and to stop the drug immediately if they appear.

Frequency not known. These were reported after the medicine was already on the market, and they are too rare to have shown up in the trials.

Source [01]Source [05]

A sudden bleed or blockage in the pituitary glandSerious

It presents as sudden severe headache, vomiting, changes in vision, eye movement problems, confusion and sometimes collapse. It needs immediate medical attention.

Rare, and reported only after marketing. The EU product information notes that most cases happened within two weeks of the first dose, and some within the first hour.

Source [05]

FitsSerious

Reported in people with epilepsy or other brain conditions, in people on other medicines that make fits more likely, and in people with none of those.

Frequency not known. Reported after marketing, in people with and without any history of fits.

Source [01]Source [11]

Raised pressure inside the skullSerious

The signs are severe or repeated headache, blurred or lost vision, swelling at the back of the eye, pain behind the eye, ringing in the ears, dizziness and nausea. The children's label tells prescribers to watch for these. The EU product information goes further and says stopping the drug should be considered if it happens.

Frequency not known. Reported after marketing, and flagged on both the EU adult label and the US children's label.

Source [05]Source [11]

Hot flushes and sweats

A sudden feeling of heat in the face, neck or chest, often with sweating. The EU product information classes it as very common — more than 1 in 10 — and says mild or moderate flushes occur in about 58% of patients. Across six endometriosis and fibroid studies, 1.8% of women stopped treatment early because of them.

The most common effect by far: 57.1% of 56 men on the monthly injection, 58.9% of 151 men on the six-monthly injection, and 84% of 166 women in the endometriosis trials.

Source [01]Source [07]

Reactions where the needle went in

Burning, stinging, bruising, redness and pain at the site. The EU product information calls burning and pins-and-needles at the site very common with the under-the-skin injection, and describes such reactions as generally mild and short-lived. Ulceration is listed as rare and tissue death as very rare.

19.2% of 151 men on the six-monthly injection into muscle had injection site pain or discomfort. In 45 children on the six-monthly injection the label records injection site reactions in 78%, and the published study reports injection site pain in 93.3%.

Source [05]Source [10]Source [11]

Low mood and swings in mood

The children's label describes crying, irritability, impatience, anger and aggression, and tells prescribers to watch for them. In adults the EU product information lists depression as uncommon, which sits oddly beside the pooled figure from the published studies. The trials and the population studies are counting different things.

In children, emotional lability in 5% of 421 on the monthly injection and psychiatric events in 22% of 45 on the six-monthly one. In men, the odds of depression were about 46% higher than in comparison groups across 38 studies of 360,650 people.

Source [11]Source [16]

Tiredness

The EU product information warns that tiredness, together with dizziness and visual disturbance, can affect the ability to drive or use machinery.

Classed as very common — more than 1 in 10 — in the EU product information. 13.2% of 151 men on the six-monthly injection into muscle.

Source [01]Source [05]

Raised blood sugar and new diabetes

The product information tells doctors to check blood sugar and HbA1c periodically, and lists worsening of existing diabetes as an uncommon reaction. Fatty liver is also named as one of the metabolic changes seen with this class.

New diabetes came at about 1.44 times the rate seen in men who were not on this class of drug, across 73,196 men followed through insurance records.

Source [05]Source [15]

These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.

NCT02234115, the single-arm trial behind the EU approval of the six-monthly Camcevi product, in men with advanced prostate cancer

50 mg leuprolide mesylate injected under the skin, on day 0 and again on day 168

336 days, in 137 men

Source [06]

FP01C-17-001, the trial behind the three-monthly Camcevi product, in men with high-risk localised or locally advanced prostate cancer

21 mg leuprorelin injected under the skin, two doses given 12 weeks apart

24 weeks, in 144 men

Source [05]

The six-monthly Lupron Depot study in men with prostate cancer that supports the US label

45 mg injected into muscle, two injections 24 weeks apart

48 weeks, in 151 men

Source [01]

The six clinical studies of the monthly gynaecology dose that the US label's safety section rests on, in women with endometriosis or fibroids

3.75 mg injected into muscle, once a month

Up to six months, in 332 women aged 18 to 53

Source [07]

The long-running study of the monthly paediatric depot in children whose puberty started far too early

300 micrograms per kilogram of body weight, but never less than 7.5 mg, injected into muscle every 28 days

A mean of 3.9 years of treatment in 55 children, then a mean of 3.5 years of follow-up

Source [09]

The phase 3 study of the six-monthly paediatric depot in central precocious puberty

45 mg injected into muscle every 24 weeks

144 weeks, in 45 children

Source [10]

What people report

• Whether the extra heart attacks and strokes are caused by the drug or by the men who are given it. The largest figures come from insurance records. The one trial that assigned men by chance let everyone see which treatment they had, and it reported heart events as a safety observation rather than as the question it was built to answer.
• How many men eventually get their testosterone back. The head-to-head trial measured it once, in 184 of the 930 men, 90 days after stopping, and then the trial ended.
• Whether the dementia signal is real. The authors of the pooled analysis say plainly that nobody has established whether the treatment causes it or is merely associated with it.
• What happens to bone, fertility and growth decades after a child is treated for early puberty. The longest of these studies followed 55 children for a mean of 3.5 years after treatment, and 45 children for 144 weeks; nothing here reaches middle age.
• How the different depot intervals compare with each other. Each was approved on its own single-arm study measured against a hormone threshold, and none of those studies compared one interval with another for survival or for side effects.
• Whether hot flushes settle down over months. Forum accounts contradict each other. Prostate Cancer UK's own page says some men improve while others keep having them for as long as treatment lasts, and the trial tables record only whether a flush happened at all.
• What effect any of this has in people taking it outside its approved uses. The EU Camcevi products are contraindicated in women and in children. Their product information records that safety and efficacy in people aged 0 to 18 have not been established, with no data available.

Is this the same thing as chemical castration?

In effect, yes. The target is the level of testosterone seen in a man whose testicles have been removed, below 50 ng/dL, and it is reached within three to four weeks. In the one head-to-head trial, 88.8% of the 308 men on leuprorelin stayed below that line for the whole 48 weeks. The difference from surgery is that it wears off, slowly, if the injections stop.

Source [05]Source [14]

Does it make things worse before it makes them better?

Yes, briefly. Because it copies the natural switch-on signal, the first injection pushes testosterone up by about half again above where it started before the switch jams shut. In men with prostate cancer that can mean a few weeks of worse bone pain or urinary trouble, and rarely pressure on the spinal cord. The product information says an anti-androgen tablet, started three days before and continued for two to three weeks, has been reported to prevent this.

Source [01]Source [05]

Does everything go back to normal when you stop?

In women, mostly and fairly quickly: normal periods had returned in 7% one month after stopping, 71% after two months and 95% after three. Bone comes back more slowly — twelve months after treatment ended, the lower spine in 16 women was still 2.2% below where it started. In men it is slower again. Ninety days after the last leuprorelin injection, mean testosterone in 184 men was 58.6 ng/dL, still below the castration threshold, while men on the comparison tablet averaged 288.4 ng/dL.

Source [07]Source [14]

Why is the endometriosis course limited to six months?

Bone. On its own, the monthly 3.75 mg injection took 3.2% off the bone density of the lower spine in 24 weeks and 6.3% in 52 weeks. Taking a norethindrone acetate tablet alongside it brought those figures down to 0.3% and 1.0%, which is why the label allows twelve months in total with the tablet and six without it.

Source [07]

Does it affect mood, memory or thinking?

Mood, clearly: the odds of depression were about 46% higher in men on this class of treatment than in comparison groups, pooled across 38 studies of 360,650 people. The children's label warns specifically about crying, irritability, anger and aggression. Memory and thinking are less settled. Pooling 11 cohort studies put dementia at about 1.21 times the rate. The authors of that analysis write that the studies they searched had conflicted, and that whether the drug causes dementia has not been answered.

Source [11]Source [16]Source [17]

Can you get hold of it without a prescription?

No. It is a depot — a gel or suspension that sets under the skin or in muscle and releases the drug over one to six months. The EU product information states that it must be given under the skin only by healthcare professionals who are familiar with the procedure. It adds that injection into an artery or a vein has to be strictly avoided. The US products are given by a healthcare provider as an injection into muscle.

Source [05]Source [07]

1. [01]DailyMed – LUPRON DEPOT (leuprolide acetate), product information with the chemical name, the flare effect and the warnings
2. [02]EMA – Camcevi (leuprorelin), EPAR: approved 24/05/2022, with study results in 137 men (2022)
3. [03]Federal Register – Determination That LUPRON (Leuprolide Acetate) Injection Was Not Withdrawn for Reasons of Safety or Effectiveness (NDA 019010, approved 9 April 1985) (2019)
4. [04]WADA International Standard Prohibited List 2026, S2.2.1 Testosterone-stimulating peptides in males (leuprorelin uttryckligen listad) (2026)
5. [05]EMA — Camcevi (leuprorelin), summary of product characteristics: testosterone falls below medical castration level within 3–4 weeks; 98.6% (141 of 143 men) below 50 ng/dL by day 28 on the 21 mg strength (2022)
6. [06]ClinicalTrials.gov NCT02234115 — single-arm phase 3 study of leuprolide mesylate 50 mg, 137 men, results posted 13 April 2018 (2018)
7. [07]DailyMed — LUPRON DEPOT 3.75 mg full prescribing information, section 14.1: amenorrhoea 74% and 98%; normal menstrual cycles resumed in 7%, 71% and 95% of women in the first three post-treatment months
8. [08]Dlugi AM et al., Lupron depot in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study, Fertil Steril 1990;54:419–27 (52 patients) (1990)
9. [09]Efficacy of leuprolide acetate 1-month depot for central precocious puberty: growth outcomes during a prospective, longitudinal study, Int J Pediatr Endocrinol 2011 (49 girls and 6 boys) (2011)
10. [10]Long-term safety, efficacy and patient-reported outcomes: phase 3 study of leuprolide acetate 6-month intramuscular depot in central precocious puberty, J Endocr Soc (45 children, 144 weeks) (2026)
11. [11]DailyMed — LUPRON DEPOT-PED, clinical studies and warnings (bone age ratio, psychiatric events, raised pressure inside the skull)
12. [12]Greenspan SL et al., Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer, J Clin Endocrinol Metab 2005: in the 30 men starting treatment, −2.5% at the total hip and −4.0% at the posteroanterior spine at 12 months (2005)
13. [13]Risk of fracture during androgen deprivation therapy among patients with prostate cancer: systematic review and meta-analysis of 16 cohort studies (519,168 men), Front Pharmacol 2021 — odds ratio 1.39 (95% CI 1.26–1.52) (2021)
14. [14]Shore ND et al., Oral relugolix for androgen-deprivation therapy in advanced prostate cancer (HERO), N Engl J Med 2020 — 930 men, 48 weeks; major adverse cardiovascular events 6.2% with leuprolide vs 2.9% with relugolix (2020)
15. [15]Keating NL, O'Malley AJ, Smith MR, Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer, J Clin Oncol 2006 (73,196 men) (2006)
16. [16]Qazi SU et al., Development of depression in patients using androgen deprivation therapy: systematic review and meta-analysis, The Prostate 2024;84(6):525–538 (2024)
17. [17]Cui H et al., Quantifying observational evidence for risk of dementia following androgen deprivation therapy: updated systematic review and meta-analysis, Prostate Cancer Prostatic Dis 2021;24(1):15–23 (2021)