When it comes to managing conditions such as endometriosis and fibroids, surgery isn’t always the best or only option. Hormonal treatments can play an important role in easing symptoms, helping prepare the body for surgery, and / or maintain symptom suppression after surgery.

One group of medications your gynaecologist may discuss is known as gonadotrophin-releasing hormone (GnRH) medications (or ‘analogues’). That’s quite a mouthful, so we’ll stick with ‘GnRH medications’ for the rest of this blog post!

GnRH medications work by changing the hormonal signals between the brain and ovaries. In doing so, they temporarily reduce hormone production from your ovaries, creating a temporary menopausal state. This can be useful when: endometriosis and / or fibroids are causing significant symptoms; other treatments haven’t provided enough symptomatic relief; or surgery is being considered.

There are a few different types of GnRH medications, and they don’t all work in exactly the same way. Nor are they right for everyone! The best option depends on the condition being treated, your symptoms, and what you’re hoping to achieve with treatment.

Let’s take a closer look at how they work and where they fit into the management of endometriosis and fibroids…

What Are GnRH Medications?

To understand how these medications work, it helps to know a little about the body’s hormonal control system.

The brain and ovaries are in constant communication. A part of the brain called the hypothalamus releases GnRH, which signals another area in the brain (called the pituitary gland) to release two hormones: luteinising hormone (LH) and follicle-stimulating hormone (FSH).

These hormones (LH and FSH) then send messages to the ovaries, helping regulate ovarian function and the production of the two main ‘female’ hormones: estrogen and progesterone. Estrogen and progesterone are important for the menstrual cycle, but they also influence the growth and activity of endometriosis and fibroids. GnRH medications interrupt this hormonal communication. By reducing ovarian hormone production, they can suppress menstrual activity, improve some hormone-related symptoms and, in the case of fibroids, temporarily reduce fibroid size.

There are two main types of GnRH medications: GnRH agonists, and GnRH antagonists. They act on the same hormonal pathway, but take different approaches.

GnRH agonists

GnRH agonists initially stimulate the pituitary gland, causing a temporary increase in the hormones that stimulate the ovaries. This can briefly increase ovarian hormone production and, in some women, cause symptoms to worsen before they improve. This is known as the ‘flare effect’.

With continued treatment (generally over the first months), the pituitary becomes less responsive to GnRH. Ovarian hormone production then falls, and menstrual bleeding and hormone-sensitive symptoms may improve.

Examples of GnRH agonists include:

• Goserelin (‘Zoladex’ 3.6 mg): a small medicinal implant injected under your skin by your GP, usually once a month
• Nafarelin (‘Synarel’): a nasal spray that is self-administered by you, twice a day
• Triptorelin (‘Diphereline’): an injectable medicine available in specific formulations and dosing schedules (eg. every month)

The formulation, frequency and duration of treatment depend on the medicine and the condition being treated.

GnRH antagonists

GnRH antagonists take a slightly different approach. Rather than initially stimulating the pituitary gland, they block GnRH receptors. This reduces the hormonal signals reaching the ovaries without the initial flare associated with GnRH agonists.

One option is ‘Ryeq’, a polypill combination tablet containing the following three medicines:

• Relugolix (a GnRH antagonist)
• Estradiol (a form of estrogen)
• Norethisterone (a progestogen)

Relugolix reduces ovarian hormone production, while the added hormones (estradiol and norethisterone) help offset some of the side-effects of low estrogen levels. This is an example of so-called ‘add-back therapy’: providing a small amount of hormones to help reduce menopausal side-effects of relugolix, such as hot flushes and night sweats.

‘Ryeqo’ is licensed in Australia for women with symptomatic endometriosis, who have previously received medical or surgical treatment. Whether it is suitable depends on individual circumstances and the relevant prescribing information.

GnRH Medications and Endometriosis

Endometriosis occurs when tissue similar to the lining of the uterus grows elsewhere in the body. Common locations include around the ovaries, pelvic lining, bowel and bladder. (Please click here to peruse the endometriosis-related blog articles Maven Centre has published previously.)

Just like the lining of the uterus, endometriosis tissue responds to a woman’ normal monthly hormonal changes, contributing to inflammation, pain and other symptoms. Reducing ovarian estrogen production can quieten endometriosis activity and improve symptoms for some women.

GnRH agonists are generally considered when other hormonal treatments haven’t provided adequate relief, have caused troublesome side-effects or aren’t suitable.

Before endometriosis surgery

Hormonal suppression is an important part of endometriosis management. Many women use hormonal treatments such as the contraceptive Pill or progestogen medications to manage symptoms, and national and international guidelines support hormonal treatment as an option. In fact, if hormonal suppression provides good symptomatic relief with minimal side-effects, many women (rightly) decide to continue with medical management, rather than proceed to surgery.

GnRH medications may be considered in selected circumstances, for example, to manage significant symptoms while waiting for surgery, or as part of an individualised treatment plan. However, it’s important to be clear about what these medications can and can’t do. Taking a GnRH medication before surgery should not be assumed to make endometriosis excision more complete, or prevent the disease from returning.

The decision to use one before surgery should take into account symptom severity, previous treatments, the planned operation and, importantly, your preferences.

After endometriosis surgery

Surgery can make a significant difference to endometriosis-related pain, but it isn’t always the end of the story. Some women continue to experience symptoms, while others develop recurrent disease. Post-operative hormonal suppression may help manage symptoms and reduce the risk of symptom recurrence, particularly when pregnancy isn’t being pursued immediately.

That doesn’t mean everyone needs a GnRH medicine after surgery. In fact, these medications aren’t routinely prescribed following endometriosis surgery. Because of their potential side-effects and impact on bone health, they’re generally considered when other options haven’t worked or aren’t suitable.

For many women, other hormonal treatments (including progestogens, and combined hormonal contraception) may be more appropriate for longer-term management.

For selected women whose symptoms remain troublesome, a GnRH medication may be worth considering. ‘Ryeqo’ may also be an option for women with symptomatic endometriosis who meet the relevant treatment criteria.

One important point: GnRH medications suppress hormonal activity; they don’t physically remove endometriosis lesions. Your post-operative treatment plan will depend on the surgery performed, any residual disease, your symptoms, previous treatment responses, and your future plans.

GnRH Medications for Fibroids

Fibroids are benign growths that develop in the muscular wall of the uterus. Depending on their size and location, they can cause heavy menstrual bleeding, iron deficiency or anaemia, pelvic pressure, pain and sometimes urinary or bowel symptoms. (Please click here to peruse the fibroid-related blog articles Maven Centre has published previously.)

Fibroids are influenced by ovarian hormones, so reducing hormone production can temporarily shrink them and reduce menstrual bleeding. The role of GnRH medications in fibroid management is particularly interesting when surgery is being considered – but they can also be useful in some women who aren’t ready for surgery or are approaching menopause.

Before fibroid surgery

GnRH agonists (‘Zoladex’ or ‘Synarel’) can be helpful before planned fibroid surgery, particularly when heavy bleeding or large fibroids are creating additional challenges. Potential benefits include:

• Less menstrual bleeding: helping control symptoms and reduce ongoing blood loss
• Improved iron levels and anaemia: with less bleeding, iron stores and haemoglobin levels may have a chance to recover before surgery
• Smaller fibroids and uterus: reducing uterine and fibroid volume may help relieve pressure symptoms and, in selected cases, make surgery less complex
• Potentially reduced blood loss during surgery: reducing fibroid size may improve some aspects of surgical planning

For example, a woman with large fibroids and significant iron deficiency may benefit from GnRH treatment before a planned myomectomy or hysterectomy. The aim might be to reduce bleeding, improve her blood count, and shrink the fibroids before her operation.

Of course, pre-treatment isn’t necessary for everyone. The possible benefits need to be weighed against side-effects, treatment duration and the type of surgery planned.

After fibroid surgery

After a myomectomy (surgery to remove fibroids while keeping the uterus), new fibroids can develop, or remaining fibroids may grow over time (up until menopause). This doesn’t happen to everyone, but it’s something to be aware of. If heavy bleeding or pressure symptoms continue after surgery, it’s worth having things reassessed. The important first step is to establish what’s causing the symptoms before deciding whether further treatment is needed.

GnRH medications aren’t routinely required after myomectomy to prevent fibroids from returning, but may be suggested to maintain symptomatic relief.

After a hysterectomy, fibroids cannot recur because the uterus has been removed surgically.

What about heavy bleeding and pressure symptoms without surgery?

GnRH medications aren’t only used around the time of surgery. In some circumstances, they can help manage fibroid symptoms even when an operation isn’t planned.

For women whose main concern is heavy menstrual bleeding, reducing blood loss can make a real difference to everyday life, and can help to address iron deficiency or anaemia. This may be particularly useful for someone approaching menopause, or needing more time to consider their treatment options.

For women whose main concern is pressure or bulk symptoms, the amount of fibroid shrinkage becomes more important. A medicine that does a good job of controlling bleeding won’t necessarily produce the greatest reduction in fibroid size.

Treatment may also be considered as a bridge to menopause, for selected women nearing the end of their reproductive years. This needs careful consideration, though, as the benefits, side-effects, cost, and likely duration of treatment all matter.

In other words, the best treatment depends not just on having fibroids, but on what symptoms those fibroids are likely to be causing.

What Are the Side-Effects?

Here’s the less appealing part. Because traditional GnRH agonists reduce estrogen levels, they can produce symptoms similar to those experienced by women going through the menopausal transition.

Possible side-effects of GnRH medications include:

• Hot flushes and night sweats (so-called ‘vasomotor symptoms’), and related sleep disturbance
• Mood changes
• Vaginal dryness and discomfort during sex
• Reduced libido
• Headaches
• Reduced bone mineral density

Not all patients experience all of these, and the severity can vary. However, the potential impact on bone health is one of the reasons treatment duration for GnRH agonists needs to be carefully considered.

As outlined above, the polypill ‘Ryeqo’ includes add-back hormones to reduce some of the effects of ovarian suppression. It isn’t suitable for everyone, however, and still requires consideration of contraindications, potential side-effects and bone health.

How does add-back therapy help?

‘Add-back therapy’ is a way of making hormonal suppression more tolerable. It involves providing small amounts of hormones alongside a GnRH agonist to reduce the side-effects associated with low estrogen levels. The aim is to maintain the benefits of treatment, while reducing problematic side-effects such as hot flushes and bone loss. For some women, add-back therapy also makes it possible to continue treatment for longer.

There is a balancing act, though. Adding hormones back can reduce the degree of uterine and fibroid shrinkage achieved. The best approach depends on the treatment goal, the medicine being used, and your individual circumstances.

Your gynaecologist will consider your medical history, bone health, risk factors and preferences when discussing the options.

Are GnRH Medications a Long-Term Option?

It’s helpful to think of GnRH medications as one part of a broader management plan, rather than a permanent cure. With traditional GnRH agonists, ovarian hormone production generally recovers after treatment stops, although the timing varies. Fibroids may grow again, and endometriosis symptoms may return.

‘Ryeqo’ may provide ongoing symptom control while treatment continues, but it also needs regular review to ensure the benefits continue to outweigh the risks.

The purpose of treatment can vary considerably. It might be to:

• Bridge the gap until surgery
• Control symptoms when surgery isn’t suitable
• Improve anaemia before an operation
• Reduce fibroid size
• Provide symptom relief when other treatments haven’t worked

Once that immediate goal has been achieved, another hormonal option may be more appropriate for longer-term management.

Choosing the Right Treatment

There isn’t one GnRH medication that is best for every woman with endometriosis or fibroids. The right choice depends on your symptoms, medical history, and what you’re hoping to achieve.

Your gynaecologist will consider things such as:

• Your symptoms and how much they affect everyday life
• Whether the main goal is pain relief, bleeding control, or fibroid shrinkage
• How you’ve responded to previous treatments
• Your tolerance of possible side-effects
• Your baseline risk of osteoporosis
• Your age and proximity to menopause
• Whether surgery is planned
• Your medical history, preferences and financial circumstances

The aim is to find an approach that provides meaningful relief without creating unnecessary side-effects or treatment burdens.

The Bottom Line

GnRH medications can be valuable tools in managing endometriosis and fibroids, particularly when symptoms are difficult to control, or surgery is being considered.

For endometriosis, they may help manage symptoms when other hormonal treatments haven’t worked or aren’t suitable. They’re not routinely needed before or after surgery, but may have a role in selected women as part of an individualised treatment plan.

For fibroids, GnRH medications can help reduce heavy bleeding, improve anaemia and shrink fibroids before surgery. They may also help manage symptoms when surgery is being delayed or isn’t suitable.

These medicines aren’t necessary for everyone, and they don’t guarantee that either condition won’t return. The best choice depends on your symptoms, treatment goals, medical history and preferences. If you’re living with endometriosis or fibroids and wondering whether a GnRH treatment might help, speak with your women’s health GP or gynaecologist. At Maven Centre, we’re happy to talk through the options, explain the pros and cons, and help you work out a treatment plan that makes sense for you!