The Future of PMDD Treatment: Neuroactive Steroids
Understanding the Challenge
Premenstrual Dysphoric Disorder (PMDD) affects around 3–8 per cent of women and can cause severe mood swings, anxiety, and low mood in the two weeks before a period. Current treatments in the UK — such as SSRIs, hormonal suppression with the combined pill or GnRH analogues, and cognitive behavioural therapy — help many women but not everyone.
Recent research has shifted focus away from hormone levels themselves and toward how the brain responds to normal hormonal changes. The key player is a naturally occurring neuroactive steroid called allopregnanolone, a metabolite of progesterone that acts on calming GABA-A receptors in the brain.
In women with PMDD, these receptors appear to be unusually sensitive to changes in allopregnanolone. Rather than feeling soothed by rising progesterone levels, they experience agitation and mood instability — a kind of “neurochemical misinterpretation” of normal hormonal signals.
How Neuroactive Steroids Work
Neuroactive steroids such as allopregnanolone and its synthetic cousins work by modulating the GABA-A receptor, which helps regulate mood and anxiety. By restoring a steady GABA response, these drugs aim to correct the underlying sensitivity that drives PMDD symptoms — instead of simply flattening hormone levels as current hormonal therapies do.
This represents a whole new way of thinking about PMDD: treating the neurobiology of hormone sensitivity rather than suppressing hormones themselves.
Brexanolone and Zuranolone Explained
Brexanolone (brand name Zulresso®) was the first licensed medicine in this class. It’s given as a 60-hour intravenous infusion and is approved in the United States for postnatal depression, a condition thought to share similar GABA-related mechanisms with PMDD.
The next step was zuranolone, an oral form of allopregnanolone that can be taken as a short course (usually 14 days). Like brexanolone, it acts on GABA-A receptors to rapidly improve mood, often within days. Zuranolone is also currently licensed in the US for postnatal and major depressive disorders.
At present, neither brexanolone nor zuranolone is licensed in the UK for any indication, and they are not available through the NHS. However, early-phase international research includes participants from Europe and the UK, and these studies will inform future MHRA and NICE reviews if results remain positive.
Emerging Pharmacological Innovations: Sepranolone
Another exciting line of research focuses on Sepranolone (also known as isopregnanolone) — a neuroactive steroid that works in a different way to other treatments. Instead of increasing GABA-A signalling like Brexanolone or Zuranolone, sepranolone is a negative allosteric modulator of the GABA-A receptor, meaning it blocks the effect of the progesterone metabolite Allopregnanolone — a key compound thought to trigger PMDD symptoms in sensitive women.
Sepranolone offers a targeted, hormone-sensitivity-based approach that may be particularly helpful for women who cannot tolerate or have not responded to SSRIs or hormonal therapies. In the UK, while sepranolone is not yet licensed for PMDD, it is part of the evolving treatment horizon and signals a shift toward precision medicine in PMDD care — matching treatments to individual brain-hormone sensitivity rather than applying a “one size fits all” model.
Early Research Findings
Initial clinical trials in women with PMDD suggest that neuroactive steroids can significantly reduce irritability, mood swings, and tension during the luteal phase. Improvements are often reported within the first treatment cycle, which is far quicker than traditional antidepressants.
Most side effects appear mild — mainly sleepiness, dizziness, or headache — and short-lived. However, larger and longer studies are needed before these medicines can be considered for NHS use.
What’s Next in PMDD Treatment Research
Over the next few years, researchers in the UK and internationally will be focusing on:
Long-term safety and tolerability.
Optimal dosing schedules, such as short luteal-phase courses versus continuous therapy.
Predictive biomarkers, to identify who is most likely to respond.
If these studies are successful, neuroactive steroids could offer an entirely new option for women who haven’t found relief with SSRIs or hormonal treatments.
At Sirona Health Ltd, I keep a close eye on these developments so I can offer patients the most up-to-date advice. While these medicines are not yet available in the UK, understanding this research helps us anticipate what the next generation of PMDD care might look like.
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Not yet. Brexanolone and zuranolone are licensed only in the United States but are being studied internationally, including by UK researchers.
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Yes. Early data suggest improvements can appear within days rather than weeks, but more evidence is needed.
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Possibly. The goal is to regulate how the brain responds to hormones, not suppress ovulation, so they could become a future first-line option.
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Most are mild — drowsiness, dizziness, or headache — but long-term safety data are still limited.
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That depends on clinical trial outcomes and MHRA/NICE review. If results remain positive, we may see UK approval later this decade.