Chemical Menopause (GnRHa Treatment)

+ More

Examples of these drugs are Lupron, Decapeptyl, Orilissa and Zoladex. They are often prescribed with HRT to provide a steady, continuous dose of hormones. GnRHa also helps confirm an accurate diagnosis of PMDD, as symptoms will resolve (i.e. not happen) when the cycle is fully suppressed. However if you have another condition which is exacerbated premenstrually (known as PME), GnRHa may not provide relief from that condition as the biological source of the issue is different to PMDD.

The chemical menopause also acts as an opportunity to test that the patient can ‘tolerate’ HRT. This is particularly important for those who have an emotional hormone sensitivity such as PMDD; studies suggest that any change in hormone levels can provoke symptoms among those patients, but that those symptoms go away again after one month of the new therapy. Therefore, patience and support are needed to evaluate the “true” effects of any treatment change. The symptoms in the first month following the start of HRT (or any changes in HRT) usually subside. So while it can be a difficult start, many can with PMDD can take HRT during chemical/surgical menopause.

This process is important as it will help to dictate if it is safe to go ahead with the surgery, and also can help decide if you need a hysterectomy in addition to ovary removal.

If the GnRHa plus hormone addback (often called a “menopause trial”) improves PMDD symptoms but the patient is unable or unwilling to continue with GnRHa treatments, patients may be offered a total hysterectomy with bilateral oophorectomy (removal of the uterus and both ovaries) to once-and-for-all remove the hormonal flux that causes symptoms. Bilateral oophorectomy (removal of the ovaries) eliminates hormone cycling, and usually eliminates cyclical symptoms in those with PMDD.

+ How effective is GnRHa treatment for PMDD?

Accurately diagnosed PMDD should see significant improvement with cycle suppression.

In trials, GnRH analogues appear to offer a significantly superior therapeutic effect compared with vitamin B6, progesterone and progestogens. This effect appears comparable with that seen for SSRIs (selective serotonin reuptake inhibitors). Data demonstrated a clinical and significant beneficial effect over placebo.

While there is some evidence to suggest that side effects can be reduced by ‘add‐back’ therapy with no demonstrable effect on efficacy, further trials are needed.

+ Why Are Hormones Added Back? I Thought That’s What We Were Trying To Get Rid Of?

PMDD is caused by a sensitivity in the brain to the hormone fluctuations that occur as part of ovulation and the luteal phase of the menstrual cycle. By ‘flattening’ out those fluctuations and ‘adding back’ a steady dose of hormones - you avoid the fluctuations and protect yourself against hot flashes, night sweats, and bone density loss, and preserve heart and brain health.

So it is actually the fluctuations we are trying to avoid - rather than the hormones themselves. Many patients with PMDD are intolerant to progesterone-based treatments so when using transdermal estrogen, the lowest possible dose of progesterone or progestogen is recommended to minimize the negative effects.

+ Do I Have To Use HRT When On This Treatment? I Do Not Do Well With Hormone Treatments

Because female bodies need some hormones to stay healthy, the doctor will usually need to prescribe stable continuous doses of estrogen (for bone and heart health) and progesterone (to prevent the uterine cancer risks associated with estrogen-only treatment). The bad news is that, during the first month of this “hormone add back” of estrogen and progesterone on top of the GnRH analogue, you may experience your PMDD symptoms again. The good news is that a recent study has found that this hormone addback-triggered “PMDD” only lasts about a month, after which the brain is able to recover from the surge of hormones and the symptoms go away despite the same levels of stable hormones. This most recent study is encouraging because it suggests that GnRH analogue therapy with stable continuous addback of estrogen and progesterone is a viable long-term treatment that can be used until the patient is through natural menopause (and does not necessarily need to lead to surgical menopause).

GnRHa is only available for use without HRT addback for six months - after this, bone loss (thinning of the bones) is a risk. After prolonged use without HRT bone density may not return to normal and you may be at risk of osteoporosis in the future so HRT is highly advised.

Chemical menopause (especially at a young age) has risks that can be reduced or eliminated with stable addback of estradiol and progesterone - sometimes referred to as “hormone replacement therapy”.

+ Should I take HRT the whole time I am on GnRH or start a few months in?

There is no set answer for this. Your doctor will likely have an established approach in the way they apply this treatment. Do discuss your concerns with them. Your doctor may want to first see how you tolerate the cycle suppression and the drop in your hormones before giving you HRT.

There is value in seeing how you do initially with complete ovarian suppression for a month or so and then seeing how you tolerate add back hormones (HRT). However, for some patients it may be easier to tolerate chemical menopause if HRT is started at the same time as GnRHa treatment.

It is not advisable to be on GnRHa treatment for longer than 6 months without estrogen HRT as the lack of estrogen can cause bone thinning and other serious health issues..

If you are using the GnRHa treatment as a ‘test’ before having ovary removal surgery for PMDD, it is highly advisable to see if you tolerate the appropriate HRT before you proceed with surgical menopause. Estrogen-therapy in surgical menopause is a crucial part in safeguarding your long term health and provides many protective benefits.

+ What if I was not prescribed HRT by my Dr?

Your doctor may want to first see how you tolerate cycle suppression and a drop in your hormones before giving you HRT. However, it would be a good idea to see if you tolerate the appropriate HRT before you proceed with surgical menopause.

If your provider is not suggesting HRT after the first 6 months, we would recommend taking them official guidance regarding the importance of estrogen therapy in chemical menopause

+ Is there a certain time in my menstrual cycle that I should start GnRHa treatment?

Ideally, treatment is started during the first five days of your menstrual cycle. Following the first injection, your next period may be lighter than usual or you may not bleed at all. The reason for giving the injection very early in the cycle is that during this part of your cycle your hormone levels are low and hopefully the treatment would start quickly and in time to flatten your cycle before you ovulate for the month - thus you would not have a cycle and therefore, no PMDD symptoms that month.

Eventually, your periods will stop for the duration of your prescribed course. However with the addition of HRT and ‘adding back’ a steady dose of hormones - (to protect yourself against hot flashes, night sweats, and bone density loss, and to preserve heart and brain health) you may have ‘withdrawal bleeds’ - for example, if you are using a progestogen treatment for 10-14 days a month, you will bleed at the end of this course. It is not a period as you will not have ovulated— but it is a withdrawal bleed. You still need to use contraception when using GnRHa treatment. Speak to your provider about the most suitable method for you.

This ‘ideal start time’ is not always possible - for example, if you live a long way from your provider or have an irregular cycle - this will not affect the efficiency of the treatment, however, it will mean you have to go through an extra cycle of PMDD if it does not stop your ovulation that month.

+ How do I know if my ovaries have totally ‘switched off’ after the injections?

When your ovarian function is shut down, your estrogen levels plummet and this low estrogen can lead to common menopausal symptoms such as hot flashes/ night sweats/ joint pain.

You should no longer have cyclical symptoms in line with your usual menstrual cycle dates.

Estrogen HRT* is added back to boost your estrogen levels to a steady level - meaning you should no longer have those uncomfortable side effects and your estrogen levels are at a protective level for your bone, heart, lung and brain health.

You will not ovulate an, therefore, should not have any ovulation signs such as the white, stretchy discharge on your usual ovulation dates.

• With a progestogen (if you have a uterus ) addback to protect your uterus from hyperplasia.

+ Do I still need to use contraceptives when on GnRHa treatment?

Yes - it is always wise to continue to use contraceptive methods when using chemical menopause - just in case!

+ 1. Ensuring accurate diagnosis

(1) This step in treatment can help make an accurate diagnosis - if your ovulation is stopped and your cycle fully suppressed, you should not experience any PMDD symptoms (though you may have menopausal symptoms if you are not on adequate estrogen HRT).

If you still continue to have symptoms this would need to be explored to look at other potential diagnosis’.

The surgery is life-changing and invasive - by skipping this step of treatment, there is a risk that you have the surgery and then find out you had PME (premenstrual exacerbation) of another condition which could of been managed via other treatment.

+ 2. Chemical menopause can be a long-term option

(2) If you trial GnRHa and tolerate it and add back HRT well then you can stay on this as a long term (and reversible) option rather than have invasive surgery and enter surgical menopause.

+ 3. Ensuring you tolerate HRT

(3) This is an opportunity to check that you can live well with stable hormone levels via HRT. We totally understand the concerns that people have when starting HRT - especially if you have a history of reacting negatively to hormone based treatments. However, HRT can help reduce or eliminate many of the physical risks that come in surgical menopause, and so it is strongly recommended that HRT is used where possible. If you choose not to use HRT, it needs to be an informed decision.

+ Did you receive adequate hormonal HRT during this GnRHa trial? Were your levels of E2 high enough?

Once you enter chemical menopause, your natural estrogen levels plummet and this low level can cause some very uncomfortable symptoms unless properly counteracted by the correct use of HRT. The level of estrogen needed will differ from person to person and is titrated depending on the individual's needs. If you are experiencing uncomfortable menopausal symptoms (e.g. hot flushes/joint pain/anxiety) then it is likely that you are not receiving adequate estrogen and you should work with your doctor in raising these levels by increasing dosage or changing delivery method (e.g. switching from patches to gel as needed).

+ Did you wait long enough to see the addback stabilize?

Estrogen therapy can take up to four weeks to begin to work, and temporary side effects can take several months to dissipate (although some can be persistent!). We recommend tracking your symptoms and side effects daily (or at least weekly) in order to have a clear visual of how symptoms are responding, and whether side effects are decreasing over time. Similarly, any changes made to your HRT regime (route, dosage or frequency) should be noted in your daily/weekly tracking document/app so that the pattern of change can be monitored objectively. We recommend waiting at least one full month on the new therapy before evaluating the new treatment or making any additional changes, since effectiveness and side effects may fluctuate prior to stabilizing again on the new treatment. This is particularly important for those who have an emotional hormone sensitivity; studies suggest that any change in hormone levels can provoke symptoms among those patients, but that those symptoms go away again after one month of the new therapy. Therefore, patience and support are needed to evaluate the “true” effects of any treatment change.

+ Was your ovarian function fully suppressed?

GnRHa treatment is used to fully suppress your ovarian function and, therefore, flatten any hormonal fluctuations that lead to PMDD symptoms. In rare cases, the GnRHa does not fully suppress the cycle and there are breakthrough symptoms. In this instance, your doctor can measure LH/FSH levels via blood tests to investigate whether or not you still have some ovarian function causing fluctuations (and therefore symptoms). These medications must suppress ovulation to be effective. If you believe that you are still ovulating, you can use at-home urine LH surge tests to determine whether you are ovulating. If you find that you are still ovulating, be sure to share this with your physician, as it means that you have not had a “fair” trial of the GnRHa, since it was not effective in producing a menopausal state.

+ Did you tolerate progesterone add-back? Are you progesterone intolerant?

When you add back hormones into your system via HRT during GnRHa treatment you would use both estrogen and progestogen. There are various ways of taking these hormones - some may be prescribed a combined treatment (such as Tibolone -a medication that mimics the actions estrogen, progesterone and testosterone). Others will take estrogen separately (as a tablet, patch, gel or spray) and use an addback progestogen for 10-14 days per month (this is usually through taking an oral tablet or in a vaginal pessary).

It is important to track your symptoms during the GnRHa treatment to see if you are indeed reacting to the progestogens, which can bring on unpleasant side effects for some which patients often report as feeling ‘PMDD-like’. If it is the progestogen you are reacting negatively to then your provider should work with you to find solutions.

Also read: How do I know if I am progesterone intolerant?

+ If you continue to have symptoms and your ovarian cycle is fully suppressed and you have adequate HRT add-back.

This will cause concern to any provider looking after your care as it would suggest that PMDD is not an accurate diagnosis for your symptoms. PME may be an alternative diagnosis that needs to be explored. Chemical menopause, or being in surgical menopause, is unlikely to improve the background symptoms, just the premenstrual exacerbation of those symptoms. It is important that the correct diagnosis is made as once the ovaries are removed there is no going back! The last thing anyone wants is for a patient to go through major surgery and not find the relief they need from symptoms.

Since the hormonal states created by chemical and surgical menopause are similar, it seems reasonable to be concerned about the outcomes of surgery if GnRH analogues are associated with a worsening of mood.