Prepared for Femtech World by Dr Emilė Radytė, neuroscientist and co-founder and CEO of Samphire Neuroscience

The short answer

Premenstrual dysphoric disorder (PMDD) does not usually result from abnormal hormone levels.

Research suggests that the brain can respond differently to expected changes in estrogen, progesterone, and the progesterone metabolite allopregnanolone.

This helps explain why blood tests can look typical while a person’s experiences remain severe. It also gives researchers a clear reason to study nervous-system treatments alongside selective serotonin reuptake inhibitors (SSRIs), hormonal treatment, and psychological care.

Why can expected hormone changes cause severe PMDD experiences?

Hormones act as signals. They interact with receptors throughout the brain and influence networks involved in mood, stress, sleep, and emotional regulation.

Two people can have similar hormonal patterns and experience those signals in different ways.

Hantsoo and Epperson (2020) reviewed evidence that PMDD involves an altered response to changing levels of allopregnanolone, which modulates gamma-aminobutyric acid type A (GABA-A) receptors. GABA helps regulate neural activity and the stress response.

In PMDD, the issue may lie in the brain’s adaptation to allopregnanolone fluctuations across the menstrual cycle.

Experimental research supports this sensitivity model. Suppressing ovarian hormone fluctuations can reduce PMDD experiences in susceptible participants, while reintroducing physiologic concentrations can bring them back.

Researchers therefore describe PMDD as a disorder of sensitivity to hormonal change, while recognizing that no single pathway explains every case.

Do normal hormone test results rule out PMDD?

No. A blood test shows whether a hormone concentration falls within an expected range at one point in time.

It cannot show how a person’s brain responds to that signal across the cycle.

Clinicians diagnose PMDD by its timing and impact, using prospective daily ratings across menstrual cycles.

The American College of Obstetricians and Gynecologists (ACOG) recognises PMDD as part of a spectrum of premenstrual disorders and recommends an individualised, multimodal approach.

Which treatments have evidence for PMDD?

ACOG’s 2023 clinical practice guideline includes hormonal and nonhormonal medicines, psychological counseling, exercise, nutritional approaches, patient education, and surgery for selected cases.

SSRIs can work faster in PMDD than they often do in major depression. Hormonal approaches can suppress ovulation or stabilize fluctuations for some patients.

No treatment works for every person. Some patients do not improve, cannot tolerate side effects, have contraindications, or prefer another route.

When that happens, clinicians and researchers need to ask which part of the biological pathway still drives the condition.

Could brain stimulation treat PMDD?

Noninvasive brain stimulation offers a plausible research direction because it can influence neural networks involved in mood regulation.

Evidence from depression cannot establish that it works for PMDD.

Researchers need PMDD-specific randomised trials that measure experiences across the cycle and report safety, adherence, and clinically meaningful outcomes.

The distinction matters. A coherent mechanism creates a hypothesis. Only indication-specific clinical evidence can establish efficacy.

Key takeaways

• PMDD can occur with hormone levels that fall within expected ranges.
• Research points to altered brain sensitivity to hormonal change, including allopregnanolone fluctuations.
• SSRIs and hormonal approaches remain evidence-based options, often as part of multimodal care.
• Brain stimulation is a research target for PMDD, not a conclusion that can be borrowed from depression studies.

Learn more at https://www.samphireneuro.com/en-us/pmdd

Sources:

Hantsoo and Epperson (2020), Allopregnanolone in premenstrual dysphoric disorder.

American College of Obstetricians and Gynecologists (2023), Management of premenstrual disorders.

Jersey is launching a pilot PMOS health check clinic for women to improve follow-up care and access to specialist support.

The clinic will operate at the Assisted Reproductive Unit in St Brelade from October, providing health checks rather than diagnosing or treating the condition.

Women with polyendocrine metabolic ovarian syndrome (PMOS) will need to see their GP before being referred to the service.

Jessica Pinel, chair of PMOS Jersey, described the service as “a good start” but said more could be done.

She said the clinic was in line with draft guidance from the UK’s National Institute for Health and Care Excellence (NICE), which advises annual checks to identify health issues associated with the condition.

Pinel was diagnosed with PMOS in 2023 after spending more than £3,100 on treatment.

She said: “We need to realise that cost may be a barrier to people getting support, even if the cost is going to their GP. But I think we do have to be grateful that we have had this service approved.

“Because the clinic is part of the government health system, it allows for referrals to be made into different pathways like endocrinology, dermatology, so it could actually allow for better support and reduce costs for women with PMOS.

“I think it’s great to see things moving forward and, for women who are newly diagnosed, there’s going to be a more joined-up approach and we’re now taking the long-term health consequences of PMOS more seriously.”

PMOS, which was renamed from polycystic ovary syndrome (PCOS) in May, is a metabolic condition that changes how the ovaries work and affects up to one in eight women, according to the UK’s NHS.

The new name was introduced to reflect the condition’s effects across the body. PMOS has been linked to infertility and weight gain.

The Jersey government said the clinic would help women access further care for PMOS and associated conditions, including type 2 diabetes.

Screening clinic nurse Corrinne Purdy said reviews would take a holistic approach, covering medication, height and weight, sleep, management of the condition, fertility aspirations and mental health.

She said: “We will see whether they’re getting on alright with their medication, how they’re feeling about themselves; we will do height and weight reviews, we will ask them questions about their sleep, how they’re managing their condition.

“We will also speak to them about any particular fertility aspirations and how they’re getting with their mental health as well.”

Purdy said PMOS had been “overlooked” for a long time and that many women struggle with associated symptoms.

The government said women who require specialist management for heavy menstrual bleeding, fertility concerns or other gynaecological conditions would be referred to the appropriate specialist service.

It said existing waiting lists for gynaecology or surgical capacity would not be affected because additional clinical capacity had been identified.

Assistant Minister for Health and Social Services Andy Howell said many women “have been suffering” with PMOS and that the trial was intended to show “that we’re taking them seriously and they’re not going to be dismissed”.

Howell said funding for the clinic would be “managed within the budget that we have at the moment, so it’s not going to cost us any more”.

The Health Department was allocated £381m for 2026 as part of the government’s 2026-2029 budget.

The clinic will also offer investigations including ultrasound scans and endometrial biopsies during the same visit.

Howell said Jersey would base its review of the service on NICE guidance, while Pinel said feedback from women using the clinic would be shared with practitioners to help improve the support provided.