This leaflet is for those who have been offered Gonadotrophin Releasing Hormone (GNRH) analogue injections or GNRH antagonist tablets, called GNRH therapy in this leaflet, to treat a gynaecological condition.
It explains;
- What conditions can be managed with hormone therapy using GNRH analogues and GNRH antagonists.
- What these medications are and how they work.
- What are the side effects.
- How long you can take them and where to seek advice if you have further questions.
Why have I been offered GNRH therapy?
These hormones are used for the management of numerous gynaecological conditions including:
- Adenomyosis.
- Endometriosis.
- Fibroids.
- Severe premenstrual syndrome also known as premenstrual dysphoric disorder (PMDD).
The aim of these hormones is to improve the symptoms caused by these conditions and your quality of life in the long term. Symptoms that can be improved include pelvic pain, painful periods, heavy periods and physical and emotional symptoms that happen in the lead up to periods also known as premenstrual symptoms.
These hormones are also offered before surgery for fibroids such as hysterectomy (removal of the womb) and myomectomy (removal of fibroids from the womb). When taken before surgery they can help control symptoms caused by fibroids and shrink the fibroids, improve your haemoglobin level and reduce the risk of bleeding during your surgery to make it safer overall.
The reason you are being offered GNRH therapy will be discussed with you at your consultation.
Types of GNRH therapy and how they are given
The most used GNRH analogue is called Leuprorelin (also known as Prostap) although you may be offered another type of GNRH analogue. Leuprorelin is given as an injection.
The two most commonly used GNRH antagonists are Relugolix (which is in a medication called Ryeqo along with estrogen and progesterone hormones) and Linzagolix. Ryeqo and Linzagolix are given as a tablet.
How do GNRH therapies work?
These are a group of synthetic hormones that mimic the menopause, which is a natural stage in life when menstrual periods stop. Unlike the menopause, the effect of GNRH therapy is temporary and wears off when stopped. You can expect an improvement in your symptoms within two months of starting treatment although it can take longer for maximal effect.
GNRH therapy reduces the production of estrogen and progesterone hormones from your ovaries. Estrogen and progesterone are responsible for causing periods, so reducing their levels in your body should stop your periods or significantly reduce the amount of bleeding.
GNRH analogue injections (such as Prostap)
When first given, there is an initial increase in estrogen hormone production. You may, therefore, experience worsening of your symptoms for the first two to three weeks before your symptoms settle. Your doctor may offer you additional treatment (progesterone hormone) to try and reduce the chance of this flare.
GNRH antagonist tablets (such as Ryeqo and Linzagolix)
These do not cause an initial increase in estrogen production so you should not get an initial flare up of your symptoms. However, in the case of Linzagolix, you may feel significant menopause type symptoms.
Your doctor will consider with you which of these treatments are best suited to you.
How often will I need to take the GNRH therapy?
GNRH therapy is best started in the first week of your period to reduce the risk of troublesome vaginal bleeding. You can start them at other times in your cycle but may find that your bleeding is initially erratic.
Leuprorelin (Prostap) injections come in two doses:
- Prostap 3.75mg (4 weekly).
- Prostap 11.25mg (12 weekly).
Your doctor or nurse will normally recommend the 4 weekly dose first. If tolerated well you can either continue having the 4 weekly injection or, for convenience, take the 12-weekly injection. These injections are usually delivered through your GP surgery.
Ryeqo (which contains a GNRH antagonist and addback HRT) is taken as a single daily tablet.
Linzagolix is taken as a single daily tablet. There are two doses:
- 100mg.
- 200mg.
The 200mg dose is more effective but may cause more side effects.
What are the side effects?
You might experience side effects associated with menopause, such as hot flushes, mood swings, depression and vaginal dryness. Your periods may not stop altogether but may reduce in volume.
Blood sugar levels may be altered during treatment. If you have diabetes, you may require more frequent monitoring of your blood sugar levels and, occasionally, you may need to adjust your diabetes medication.
If taken for more than 6 months, there is an increased chance of brittle bone disease also known as osteoporosis.
Uncommonly, you can develop a severe rash, severe itching (local allergic reaction) at the injection site.
Rarely you can develop shortness of breath or difficulty breathing (anaphylactic reaction) after an injection. Please attend your nearest Emergency department if you get such symptoms.
Common (may affect up to 1 in 10 people) side effects
- Difficulty sleeping, headaches or hot flushes.
- ‘Brain fog’, weight changes, mood changes.
- Joint pain, muscle weakness, breast tenderness, vaginal dryness.
- Skin reactions at the injection site.
Uncommon (may affect more than 1 in 100 people)
Loss of appetite, changes in blood lipids (cholesterol), altered vision, pounding heartbeats, diarrhoea, vomiting, abnormalities in liver blood tests, hair loss, muscle aches, fever, chills or tiredness.
How can these side effects be managed?
These side effects can be managed with the use of Hormone Replacement Therapy (HRT). Tibolone (2.5 milligram tablet daily) is the first line HRT medication offered but other HRT treatments may be recommended. The dose of HRT dose is small so that it does not reduce the effectiveness of the GnRH treatment.
You might be offered HRT when you are taking Leuprorelin (Prostap) injections or Linzagolix tablets from the beginning, if you develop menopause symptoms or if you are taking those hormone therapies for more than 6 months.
The Ryeqo tablet already contains HRT so you do not need to take additional HRT medication.
You may not be suitable for HRT or you may opt not to take it. If that is the case, you might be advised to take your hormone therapy in six-month intervals to allow your bones to rebuild strength or you may be offered a bone density scan (also known as a DEXA scan – Dual Energy X-ray Absorptiometry) about 12 to 18 months after you have started your treatment and at regular intervals after that.
You should also consider adjusting for any risk factors for osteoporosis such as stop smoking, doing regular weight bearing exercises, getting regular exposure to the sun, reducing alcohol intake and taking recommended dietary Vitamin D and calcium.
Pregnancy and Contraception
Although the GnRH injections tend to prevent ovulation they are not licensed as contraception (birth control). Please make sure that you are on a suitable contraceptive such as condoms or diaphragm or non-hormonal (copper) coil if you are sexually active. In some cases the hormonal coil, such as Mirena coil, can be used.
Ryeqo is an effective contraceptive after one month provided it is used consistently and regularly, as advised.
Injections will not be given if you are pregnant.
How long can I continue taking GNRH therapy?
They can be used long term. However, if you do, you are likely to be advised to used HRT to reduce the risk of developing osteoporosis and to help promote good heart health.
What to expect when I stop using GNRH therapy?
If you have not gone through the menopause, your periods will normally return within 6 – 10 weeks after the injection has worn off and may return sooner if you are taking tablets.
The longer the course of treatment the longer it may take for periods to return. The symptoms related to your gynaecological condition may also return.
There is no known direct negative impact of treatment on your fertility. However, if you are on long term GNRH therapy you will be older when you stop treatment and increasing age affects your fertility.
If you stop GNRH therapy around the time of your natural menopause you may find that your periods are far less frequent. If you have gone through the menopause while on the hormone therapy, your periods will not return.
For more information
Please speak to your doctor about this treatment if you have any further questions.