Leuprolide (Lupron): side effects & how it works

Author: Jessica Lloyd
Senior Vulvovaginal Specialist Naturopath | BHSc(N) | ISSVD, ISSWSH, BSSM, ATMS

Last reviewed: July 5, 2026

Leuprolide (brand name Lupron) is a hormone-modulating medication used to manage endometriosis and fibroids, treat precocious puberty (early puberty) in children, and prepare the ovaries during IVF. It works by switching off your own oestrogen production, which is what makes it useful and also what causes most of its side effects.¹

Leuprolide is a gonadotropin-releasing hormone (GnRH) agonist. It is used alone or with a small amount of replacement hormone, known as ‘add-back’ therapy, to soften the side effects of a very low-oestrogen state.

Brand names for leuprolide include Lupron Depot, Eligard, Fensolvi and Lupron Depot-PED. Other GnRH agonists work in the same way but go by names such as goserelin, triptorelin, buserelin or nafarelin.

How leuprolide works: a deliberate oestrogen shut-off

GnRH agonists all work in the same way. At first they stimulate the pituitary gland, then, with continuous dosing, they switch it off, so the ovaries stop being told to make oestrogen.¹

The endometrial lining relies on oestrogen. When oestrogen is not present, the lining cannot develop. Without it, including endometriosis lesions attached to internal organs, menstrual bleeding slows and stops after about two months for most users.

In effect, leuprolide puts the body into a temporary, reversible menopause. That is the whole point of the treatment, and it is also why the side effects look so much like menopause.

How leuprolide is given

Leuprolide comes as a long-acting suspension injected into the muscle. How often you have it depends on your doctor and the type used, ranging from once a month to every three, four or six months. Treatment is often started around three to four days into a menstrual period, though this can vary from person to person.

What to expect after starting leuprolide

Sometimes a menstrual bleed will happen soon after starting treatment. The lining already built up in the uterus loses its oestrogen source and ‘falls off’, which is what a normal period is. Spotting can also happen one to two weeks after the first dose.

Symptoms may get worse in the first couple of weeks. Oestrogen can rise briefly before it falls, which flares oestrogen-related symptoms for a short time. As oestrogen is gradually cleared, symptoms settle and improve.¹

Leuprolide for endometriosis

Leuprolide may be used alone or with norethindrone to manage the symptoms of endometriosis, such as heavy, painful periods.

The typical treatment period is three to six months. A three-month course may be as effective for pain relief as a six-month course, but six-month courses tend to delay the return of symptoms for longer.²

It is also sometimes given after surgery for endometriosis, where it can help delay the return of the disease.³

In Germany, 12-month treatment has been approved with add-back therapy of 5mg of norethisterone per day.

Leuprolide for uterine fibroids

Leuprolide can be used to manage uterine fibroids, which also shrink when oestrogen is low. It is often used for a short stretch before surgery to reduce fibroid size and settle heavy bleeding, which can make an operation easier and safer.

Leuprolide in IVF: the down-regulation protocol

Leuprolide, usually Lupron, is used in IVF to prevent premature ovulation during the ovarian stimulation phase. This is known as the down-regulation protocol.

GnRH agonists and antagonists are both used to hold off premature ovulation. The difference is that agonists like Lupron take about a week to start working, while GnRH antagonists act very quickly. Antagonists are used in the antagonist protocol, rather than the down-regulation protocol.

Lupron in IVF is used for about two weeks.

For people with endometriosis specifically, a longer stretch of down-regulation before IVF has been studied as a way to improve the chance of pregnancy.⁴

Ovulation and periods while using leuprolide

Whether ovulation and periods happen during treatment is different for everyone, but for most people they become much less likely.

Most people using leuprolide injections will have a period within 6-10 weeks of the last injection. With GnRH agonist sprays such as buserelin or nafarelin, a period will usually come within 4-6 weeks of the last spray.

Pregnancy and breastfeeding with leuprolide

Leuprolide is not for use during pregnancy, since a pregnancy needs a lot of oestrogen. A pregnancy test is usually done before starting, because the drug can cause loss of a pregnancy.

It is generally difficult to get pregnant while using a GnRH agonist, but it is not impossible, so non-hormonal birth control is recommended while on leuprolide. It can cause miscarriage or foetal abnormalities. GnRH agonists are not a treatment for infertility.

Some GnRH agonists pass into breast milk, so using these drugs while breastfeeding is not recommended.

What is ‘add-back’ medication?

Some people also take what is known as add-back medication to reduce or prevent GnRH agonist side effects. This may be low-dose oestrogen, a progestin, or tibolone.

These doses are small, so they don’t cancel out the effect of leuprolide, but they can ease some of the more uncomfortable effects of low oestrogen, such as vaginal dryness and hot flushes. Add-back with a progestin like norethindrone has been shown to protect against bone loss while still controlling endometriosis pain, which is what makes longer courses possible.⁶

Add-back can be really helpful, so ask about it if you aren’t offered it.

Loss of bone density

Bone is constantly breaking down and rebuilding, and oestrogen helps keep bone density high. When oestrogen drops, breakdown outpaces rebuilding, so bones become less dense. The decrease in bone density after six months is 4-6 per cent.⁵

Once treatment stops, bone density rebuilds over the following 18-24 months, and the lost bone is replaced. If you are already at greater risk of osteoporosis, treatment with a GnRH agonist should be weighed up carefully, and add-back therapy is especially worth discussing.

Vaginal and urinary side effects of leuprolide

Losing oestrogen has a big effect on the vagina and can bring on uncomfortable or painful symptoms. The vagina becomes, in effect, postmenopausal, so the symptoms match what is known as genitourinary syndrome of menopause (GSM).⁷

Vaginal and urinary symptoms are common on GnRH agonists and include:

Vaginal dryness, itching and irritation
Microbiome disturbances and vaginal infections such as bacterial vaginosis and aerobic vaginitis
Vaginal odour and unusual discharge
Thinning, easily damaged tissue and shrinking labial tissue
Painful sex and penetration (dyspareunia) and difficulty using tampons
More frequent urinary tract infections, urinary incontinence and urethritis

Symptoms can be mild to severe, and at least one or two are likely, since the drug effectively makes the body postmenopausal. The good news is these usually settle once treatment stops, and there is a lot you can do to feel more comfortable in the meantime.

Common side effects of leuprolide

Vaginal discharge, dryness and itching
Reduced bone density, with increased risk of broken bones and osteoporosis
Worsening symptoms of diabetes or raised blood sugar (hyperglycaemia)
Mid-cycle spotting or bleeding, and menstrual bleeding
Reduced libido and sexual function
Fatigue
Hot flushes with sweating
Tender or painful breasts, and changes in breast size
Swollen hands, feet, ankles or lower legs
Pain, burning or tingling in the hands or feet
Injection site symptoms: pain, burning, bruising, redness or hardening
Weight fluctuations
Muscle and joint pain
Cold or flu-like symptoms (runny nose, cough, sore throat) and fever
Stomach pain, constipation and digestive problems
Headaches
Acne
Low mood and depression
Unstable mood, irritability and difficulty with emotional control
Anxiety and nervousness
A sense of discomfort or unease
Memory issues
Worsening hyperlipidaemia (raised blood fats)
Worsening cirrhosis or non-alcoholic liver disease
In children, signs of sexual development may briefly worsen in the first few weeks, including spotting or a period

Natural and root-cause support for leuprolide side effects

Leuprolide does an important job, and for many people it is the right choice. It is also hard on the body, so supporting yourself through it is well worth the effort. None of the ideas below interfere with the medication. They are about comfort, protecting your bones, and looking after the tissue and microbiome while your oestrogen is switched off.

Easing vaginal dryness and irritation without touching your hormones

We see a fair few people with exactly these symptoms, and a good number are going through IVF, where leuprolide is used to quieten the ovaries before egg collection. The low oestrogen can leave them with new dryness or BV. What we reach for is local support, matched to whatever the symptoms are, that soothes and rebuilds the tissue without changing systemic oestrogen, so it eases the discomfort without working against what the drug is there to do. It is the same approach we would use for any low-oestrogen situation, whether that is breastfeeding, trans men on testosterone, or someone on this drug for endometriosis, fibroids or cancer.

The building blocks we tend to work with:

A fennel pessary to soothe and support oestrogen-starved tissue
Sea buckthorn oil, used on the tissue and also taken orally, which improved the integrity of vaginal tissue in a randomised, placebo-controlled trial without changing systemic hormones⁸
Vaginal lactulose, a prebiotic that feeds protective lactobacilli
A vaginal probiotic to help rebuild the protective bacteria that low oestrogen tends to strip away

Which of these you use, and in what order, depends on your symptoms. Plain, unperfumed moisturisers and lubricants help day to day, and it is worth keeping an eye out for BV or aerobic vaginitis, since the microbiome shifts when oestrogen and its glycogen supply fall away. If you develop a new odour, unusual discharge or itch, that is worth checking rather than assuming it is ‘just’ dryness.

Protecting your bones during treatment

Because bone density drops while oestrogen is low, this is the time to give your skeleton every advantage. Weight-bearing and resistance exercise are the strongest lever you have, as they signal bone to hold onto its density.

Alongside movement, make sure you are covered for vitamin D, vitamin K2, calcium from food, and magnesium, which all play a part in bone building. Add-back therapy is the medical piece that directly limits bone loss, so it is worth raising with your doctor if it hasn’t been offered, especially for longer courses.

The bigger endometriosis picture

Leuprolide suppresses endometriosis, but it does not cure it, and symptoms tend to return once the drug stops. That is why the time on treatment is a good window to work on the drivers underneath, so you are in a stronger position afterwards.

Endometriosis is an oestrogen-fuelled, inflammatory condition, so the underlying picture usually involves inflammation and how the body processes and clears oestrogen through the gut. Supporting digestion and regular bowel movements, eating for lower inflammation, and getting enough fibre all help the body clear oestrogen efficiently. Our practitioners can help you build a plan for treating endometriosis that runs alongside your medical care.

One honest caution: because the whole point of leuprolide is to lower oestrogen, it is not the time to load up on oestrogenic herbs or high-dose phyto-oestrogens in the hope of ‘topping up’, as that can work against the treatment for endometriosis or fibroids. Local tissue support is chosen precisely because it helps the vaginal tissue without raising whole-body oestrogen. If you want to add anything oestrogenic, talk it through with your team first.

If you are looking for support during treatment for endometriosis or want options with fewer side effects, book in with one of our specialist naturopathic practitioners. We can help, and there are options.

Frequently asked questions

Does leuprolide put you into menopause?

It creates a temporary, reversible menopause by switching off oestrogen production. That is why the side effects, from hot flushes to vaginal dryness, look so much like the real thing. For most people, normal hormone function returns once treatment stops.

Will my periods come back after leuprolide?

Usually, yes. Most people using injections have a period within 6-10 weeks of the last injection, and within 4-6 weeks of the last spray for sprays such as buserelin or nafarelin.

Can I get pregnant while on leuprolide?

It is difficult but not impossible, and leuprolide can harm a pregnancy, so non-hormonal birth control is recommended while you are using it. GnRH agonists are not a treatment for infertility, though they are used as one step within some IVF protocols.

How do I cope with vaginal dryness on leuprolide?

Local, non-hormonal support works well: a plain vaginal moisturiser and lubricant for day-to-day comfort, plus tissue-soothing options such as a fennel pessary and sea buckthorn oil, and prebiotic and probiotic support to keep the microbiome steady. These help the tissue without raising systemic oestrogen. Add-back therapy from your doctor is another option worth asking about.

Does leuprolide cause permanent bone loss?

Bone density falls by around 4-6 per cent over six months, but for most people it rebuilds over the 18-24 months after treatment stops. Add-back therapy, weight-bearing exercise and good nutrient cover all help protect your bones during treatment.

This article is general information and not a substitute for personalised medical advice. If you are worried about your symptoms or how to manage treatment, please see your prescribing doctor or an experienced practitioner.