Leuprolide is a hormone-modulating treatment used to manage the symptoms of endometriosis and fibroids, treat precocious puberty (early puberty) in children, and in IVF assisted fertility treatments.
Leuprolide is a gonadotropin-releasing hormone (GnRH) agonist which works to decrease specific hormones in the body. Leuprolide injections are used alone or with other medication, known as ‘add-back’ therapy, to replace some hormone.
Brand names for leuprolide include Eligard, Lupron Depot, Fensolvi, and Lupron Depot-PED. All GnRH agonists work in the same way but may have different names such as goserelin or triptorelin.
Endometriosis treatment with leuprolide
Leuprolide may be used alone or with norethindrone to manage symptoms of endometriosis, such as heavy, painful periods.
Uterine fibroid treatment with leuprolide
Leuprolide can be used to manage uterine fibroids.
Down Regulation Protocol in IVF treatments
Lueprolide, usually Lupron, is used in IVF protocols 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 suppress premature ovulation, with the difference being agonists (like Lupron) take about a week to start to work, while GnRH antagonists act very quickly. Antagonists are known as the Antagonist Protocol, rather than the Down Regulation Protocol.
Lupron in IVF is used for about two weeks.
How leuprolide works – loss of oestrogen production
GnRH agonists all work in the same way and block the production of oestrogen via several mechanisms. The endometrial lining relies on oestrogen, so when oestrogen is not present, the endometrial lining cannot develop.
Without the endometrial lining, including endometriosis lesions adhered to internal organs, menstrual bleeding slows and stops after about two months for most users.
What to expect after starting leuprolide
Sometimes a menstrual bleed will occur soon after starting treatment, as the buildup of endometrial lining already present in the uterus loses its oestrogen source, and ‘falls off’ (which is what causes a normal period). Spotting can also occur 1-2 weeks after commencing treatment.
Symptoms may worsen in the first two weeks, as oestrogen can rise initially, worsening oestrogen-related symptoms. As oestrogen is gradually cleared from the body, symptoms improve.
Ovulation and periods while using leuprolide
Whether ovulation and menstrual periods occur during treatment is different for everyone but generally not as likely for most people.
Most leuprolide injection users will have a period within 6-10 weeks of the last injection. When using GnRH agonist sprays such as buserelin or nafarelin, a period will likely come within 4-6 weeks of the last spray.
Pregnancy and breastfeeding with leuprolide
Leuprolide is not for use during pregnancy since a pregnancy requires a lot of oestrogen production. A test will likely be performed prior to administration since this will result in the likely loss of the pregnancy.
Generally, it is difficult to get pregnant while using a GnRH agonist, but it’s not impossible, so it’s recommended to use non-hormonal birth control while on leuprolide. It can cause miscarriage or foetal abnormalities.
GnRH agonists are not a treatment for infertility.
Some GnRH agonists are transferred in breast milk, and using these drugs while breastfeeding is not recommended.
What is ‘add-back’ medication?
Some people also take what’s known as add-back medication to reduce or prevent GnRH agonist side effects, which may include low-dose oestrogen, progestin or tibolone.
These medications are small doses, so they don’t reduce the effect of leuprolide, but they can combat some of the more uncomfortable side effects of having low oestrogen, such as vaginal dryness.
Vaginal and urinary tract side effects from using leuprolide or other GnRH agonists
The loss of oestrogen from the body has a huge impact on the vagina and can create uncomfortable or painful vaginal symptoms. The vagina becomes, in effect, postmenopausal, and therefore the symptoms are equivalent, known as genitourinary symptoms of menopause (GSM).
Vaginal and urinary tract symptoms are common when using GnRH agonists and include:
- Vaginal dryness
- Itching
- Irritation
- Microbiome disturbances and vaginal infections (bacterial vaginosis, aerobic vaginitis)
- Vaginal odour
- Unusual discharge
- Thinning tissue
- Easily damaged tissue
- Painful sex and penetration (dyspareunia)
- Difficulty using tampons
- Shrinking labial tissue
- More frequent urinary tract infections
- Urinary incontinence
- Urethritis
Side effects can be mild to severe, and at least one or two symptoms are likely to be experienced since the drug effectively puts the body into a state of being postmenopausal. Add-back medication can be really helpful, so ask for it if you aren’t prescribed it.
Side effects tend to disappear after treatment ceases.
Loss of bone density
Bone matrix is constantly breaking down and regenerating, with oestrogen helping to keep bone density high. When oestrogen drops off, the rate of bone matrix breakdown increases beyond regeneration, so bones become less dense and more brittle. The decrease in bone density after six months is 4-6 per cent.
Once treatment ceases, bone density regenerates over the coming 18-24 months, and the lost bone is replaced. If a user is at greater risk of osteoporosis, treatment with GnRH agonists should be carefully evaluated.
Add-back therapy can be helpful here.
Dosage and effectiveness of leuprolide for endometriosis
The typical treatment period with leuprolide is 3-6 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.1–3
In Germany, 12-month treatment has been approved with add-back therapy of 5mg of norethisterone per day).
Administration of leuprolide
Leuprolide comes as a long-acting suspension injected into the muscle, with the frequency of doses determined by the doctor and the type of suspension used. Some injections are administered once a month, while others every 3, 4 or 6 months.
The typical starting time for leuprolide is 3-4 days into a menstrual period, but this may vary depending on the person.
Common side effects of leuprolide
- Vaginal discharge
- Vaginal dryness
- Vaginal itching
- Reduced bone density, increased risk of broken bones and osteoporosis
- Worsening symptoms of diabetes or hyperglycaemia (raised blood sugar)
- Mid-cycle spotting or bleeding
- Menstrual bleeding
- Reduced libido
- Reduced sexual function
- Fatigue
- Hot flashes with sweating
- Tender breasts or breast pain
- Change 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 pain
- Joint pain
- Cold or flu-like symptoms (runny nose, cough, sore throat)
- Fever
- Stomach pain
- Constipation, digestive problems
- Headaches
- Acne
- Mental health issues such as depression
- Unstable mood, moodiness, lack of emotional control
- Anxiety, nervousness
- Sense of discomfort or uneasiness
- Memory issues
- Worsening hyperlipidemia
- Worsening cirrhosis of the liver or non-alcoholic liver disease
- In children, symptoms of sexual development may worsen in the first few weeks, including spotting or menstruation occurring
Holistic treatments for endometriosis symptoms
If you’re looking for support during treatment for endometriosis or treatments with fewer side effects, book in with one of our specialist naturopathic practitioners. We can help, and there are options.
References4–7
- 1.Zheng Q, Mao H, Xu Y, Zhao J, Wei X, Liu P. Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis. Arch Gynecol Obstet. Published online April 6, 2016:201-207. doi:10.1007/s00404-016-4085-y
- 2.Busacca M, Somigliana E, Bianchi S, et al. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III–IV: a randomized controlled trial. Human Reproduction. Published online November 2001:2399-2402. doi:10.1093/humrep/16.11.2399
- 3.Hornstein M, Yuzpe A, Burry K, Heinrichs L, Buttram V, Orwoll E. Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Fertil Steril. 1995;63(5):955-962. https://www.ncbi.nlm.nih.gov/pubmed/7720940
- 4.Farmer JE, Prentice A, Breeze A, et al. Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database of Systematic Reviews. Published online October 20, 2003. doi:10.1002/14651858.cd001297
- 5.Jee BC, Lee JY, Suh CS, Kim SH, Choi YM, Moon SY. Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery. Fertility and Sterility. Published online January 2009:40-45. doi:10.1016/j.fertnstert.2007.11.027
- 6.Sallam HN, Garcia-Velasco JA, Dias S, Arici A, Abou-Setta AM, Jaafar SH. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database of Systematic Reviews. Published online January 25, 2006. doi:10.1002/14651858.cd004635.pub2
- 7.Brown J, Kives S, Akhtar M. Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database of Systematic Reviews. Published online March 14, 2012. doi:10.1002/14651858.cd002122.pub2
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