How do hormone therapies like gonadotropin impact PMS symptoms?

For many women, the premenstrual phase of the menstrual cycle brings a predictable array of physical and emotional symptoms, collectively known as Premenstrual Syndrome (PMS). These can range from bloating and breast tenderness to irritability and mood swings. However, for some, these symptoms escalate into a severe and debilitating condition known as Premenstrual Dysphoric Disorder (PMDD), characterized by profound emotional distress, intense anxiety, depression, and significant functional impairment. Both PMS and PMDD are intricately linked to the fluctuating levels of ovarian hormones—estrogen and progesterone—during the luteal phase of the menstrual cycle.

When standard treatments like lifestyle changes, nutritional supplements, or even selective serotonin reuptake inhibitors (SSRIs) do not provide sufficient relief, healthcare providers may consider more potent hormonal therapies. Among these, Gonadotropin-Releasing Hormone (GnRH) agonists stand out as a powerful option. But how do these therapies impact PMS and PMDD symptoms? This blog will explore their mechanism of action, their effectiveness, and important considerations for their use.

The Role of Hormones in PMS and PMDD

To understand how GnRH agonists work, it's essential to briefly revisit the hormonal cascade that drives the menstrual cycle and influences PMS/PMDD.

The hypothalamus in the brain releases GnRH, which signals the pituitary gland to release two other crucial hormones: Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH and LH, in turn, stimulate the ovaries to produce estrogen and progesterone. It is the cyclical rise and fall of these ovarian hormones, particularly the sharp drop in estrogen and progesterone after ovulation, that is believed to trigger the symptoms of PMS and PMDD in susceptible individuals. The brain, especially the areas involved in mood regulation (like the serotonin system), appears to be hypersensitive to these normal hormonal fluctuations.

How GnRH Agonists Work :

GnRH agonists are synthetic versions of the naturally occurring GnRH hormone. Ironically, despite mimicking GnRH, their continuous administration initially causes a temporary surge in FSH and LH, followed by a profound and sustained downregulation of the pituitary gland's receptors. This downregulation effectively switches off the pituitary's signal to the ovaries.

The result? The ovaries stop producing estrogen and progesterone. This creates a state of "medical menopause" or "chemical menopause" where ovarian hormone levels are significantly suppressed to very low, postmenopausal levels (Chelsea and Westminster Hospital NHS Foundation Trust, n.d.).

By essentially putting the ovaries to sleep and eliminating the cyclical hormonal fluctuations, GnRH agonists remove the trigger for PMS and PMDD symptoms. Without the rollercoaster of estrogen and progesterone, the brain's sensitivity to these shifts becomes irrelevant, leading to a profound reduction or even complete cessation of premenstrual symptoms.

Effectiveness in Managing PMS and PMDD Symptoms

GnRH agonists are highly effective in alleviating the severe symptoms of PMDD and severe PMS when other treatments have failed. Clinical studies consistently demonstrate their ability to eliminate or significantly reduce:

• Mood Symptoms: Irritability, anger, depression, anxiety, panic attacks, feelings of hopelessness, and mood swings are often dramatically improved.

• Physical Symptoms: Bloating, breast tenderness, headaches, fatigue, and muscle aches also tend to resolve due to the suppression of ovarian activity.

Because they address the root cause of the cyclical symptoms (hormonal fluctuations), they can provide significant relief for women whose lives are severely impacted by these conditions. Their effectiveness makes them a valuable option for diagnostic purposes as well; if symptoms resolve entirely while on a GnRH agonist, it strongly confirms a hormonal sensitivity driving the symptoms.

Important Considerations and "Add-Back" Therapy

While highly effective, GnRH agonists are not typically a first-line treatment due to their side effects, which mimic those of natural menopause. These can include:

• Hot flashes and night sweats

• Vaginal dryness

• Loss of libido

• Bone density loss (osteoporosis risk with long-term use)

• Headaches

• Mood changes (though often different from PMDD moods)

To mitigate these menopausal side effects, particularly the risk of bone density loss, GnRH agonists are almost always prescribed with "add-back" therapy. This involves taking low doses of estrogen and/or progesterone (or a combination) alongside the GnRH agonist (Chelsea and Westminster Hospital NHS Foundation Trust, n.d.). The aim of add-back therapy is to provide just enough hormone to alleviate the menopausal side effects and protect bone health, without restarting the cyclical fluctuations that trigger PMDD/PMS symptoms. This strategy allows women to experience the benefits of ovarian suppression with fewer adverse effects.

Who is a Candidate for GnRH Agonist Therapy?

GnRH agonists are generally reserved for:

• Women with severe PMDD or very severe PMS who have not found adequate relief from other first-line treatments, such as SSRIs, hormonal contraceptives, or lifestyle modifications.

• Cases where a definitive diagnosis of PMDD is needed, as the complete resolution of symptoms confirms the hormonal link.

• Short-term use or for diagnostic purposes, although with appropriate add-back therapy, longer-term use may be considered under careful medical supervision.

It is crucial to have a thorough discussion with a healthcare provider specializing in women's health or reproductive endocrinology to determine if GnRH agonist therapy is a suitable option, considering your individual health profile, symptom severity, and treatment goals.

Related Articles

At HealCycle, we believe in empowering you with knowledge about your hormonal health journey. Here are some related articles from our blog that can provide further insights:

• What Treatments are Available for My PMDD Symptoms?: This article offers a broad overview of PMDD treatments, placing GnRH agonists within the wider spectrum of available options.

• Do PMDD Symptoms Get Worse During Perimenopause?: Explore how hormonal fluctuations during perimenopause can interact with PMDD, which can sometimes lead to a consideration of GnRH agonists if symptoms become unmanageable.

• How Do My Hormones Make Me Feel So Up and Down?: This post delves into the biological mechanisms behind hormonal mood swings, providing context for why disrupting the hormonal cycle can alleviate PMDD.

Conclusion

Hormone therapies like Gonadotropin-Releasing Hormone (GnRH) agonists offer a powerful and effective treatment option for women with severe PMS and PMDD, particularly when other less invasive methods have not provided sufficient relief. By temporarily shutting down ovarian hormone production, GnRH agonists eliminate the cyclical fluctuations that trigger symptoms, providing profound relief. While associated with menopausal side effects, the use of "add-back" therapy can significantly mitigate these, making this a viable path for many. Consulting with a specialized healthcare provider is essential to determine if GnRH agonist therapy is the right choice for your individual needs and to develop a comprehensive management plan.

Disclaimer:

The information provided in this blog post is for informational purposes only and does not constitute medical advice. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your qualified healthcare provider with any questions you may have regarding a medical condition or before starting any new treatment or making any changes to existing medical care.

References

Chelsea and Westminster Hospital NHS Foundation Trust. (n.d.). Gonadotropin releasing hormone agonists for PMS. Chelsea and Westminster Hospital NHS Foundation Trust.

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Wagner-Schuman, M., Ramezani, N., Lathrop, K. D., & Freeman, E. W. (2023). What's stopping us? Using GnRH analogs with stable hormone addback in treatment-resistant premenstrual dysphoric disorder: Practical guidelines and risk-benefit analysis for long-term therapy. Journal of Clinical Psychiatry, 84(4).

Wyatt, K., Dimmock, P., Ismail, K., Poole, C., & O'Brien, P. M. S. (2004). The effectiveness of GnRHa with and without 'add-back' therapy in treating premenstrual syndrome: A meta-analysis. British Journal of Obstetrics and Gynaecology, 111(9), 909-917.

Yonkers, K. A., O'Brien, P. M. S., & Eriksson, E. (2008). Premenstrual dysphoric disorder. New England Journal of Medicine, 358(15), 1486-1493.