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.

Thousands of UK women develop undiagnosed PTSD after childbirth each year, with at least 15,000 cases going undetected, researchers say.

The true number could be double that or more, according to an evidence review of childbirth-related post-traumatic stress disorder (PTSD).

PTSD can involve symptoms including nightmares, flashbacks, anxiety and persistent negative thoughts. Research estimates suggest between 5 and 5.9 per cent of women giving birth develop the condition.

Doctors at the University of East Anglia’s medical school reviewed existing data on births, PTSD prevalence and six-week postnatal GP appointments to estimate how many cases are going undiagnosed.

They said many GPs mistake childbirth-related PTSD for postnatal depression, potentially resulting in women receiving treatment that is not appropriate for PTSD.

Research has estimated that fewer than half of women with postnatal PTSD symptoms are diagnosed and receive NHS care.

Lead author Dr Megan Foreman, who is also a GP, said: “The Office for National Statistics figure for the 2025 live birthrate in England and Wales, not including Scotland and Northern Ireland, was 585,396.

“This figure does not include stillbirths and miscarriages, which are significant risk factors for childbirth-related PTSD.

“Therefore, at 5 per cent of the 2025 ONS birthrate for England and Wales (29,269), combined with the evidence from Moran et al that less than 50 per cent of women with PTSD symptoms postnatally are referred for specialist perinatal mental health support, a UK figure greater than 15,000 women, but potentially in the tens of thousands, would be justifiable based on the available evidence.”

The researchers said cases are being missed during the NHS six-week postnatal check, which assesses the health of both the mother and baby.

There is no approved framework for assessing a woman’s risk of childbirth-related PTSD during these appointments, they said.

Assessing a newborn’s health can also make it harder to focus on the mother’s mental health, particularly if she attends the appointment alone with her baby.

The researchers also noted that some women may not feel able to discuss a traumatic birth soon afterwards because doing so could retrigger the experience.

The review cited UK research in which half of GPs recognised trauma-related features in case examples of childbirth-related PTSD, but postnatal depression remained their most common diagnosis.

The authors said misdiagnosis could be detrimental because women may be prescribed antidepressants, which are not as effective for treating PTSD as psychological therapy.

Treating depression alone may also fail to improve coexisting childbirth-related PTSD.

Identifying the condition is particularly important because both PTSD and postnatal depression are associated with an increased risk of suicide, the most common cause of death among women in the year after giving birth, the authors said.

The review also said untreated childbirth-related PTSD can affect women and their families, contribute to further healthcare needs, lead to avoidance of doctors and hospitals and influence decisions around future pregnancies.

Angela McConville, chief executive of parenting charity NCT, said: “The possibility that so many women could be living with undiagnosed PTSD after birth is deeply concerning.

“PTSD after birth is a serious and often overlooked condition that can have a profound impact on women and new mothers, as well as those around them.

“No one should have to reach crisis point before they are listened to and able to access support.

“These findings are a powerful reminder that birth trauma does not end when care in hospital ends.

“When trauma goes unrecognised or unsupported, the effects can be felt across relationships, family life and wellbeing for months or even years.”

Women entering pregnancy with multiple conditions face a 20 per cent higher miscarriage risk and around four times the risk of anxiety and depression, new research has revealed.

The observational study found women with two or more pre-existing long-term physical or mental health conditions also had a 69 per cent higher risk of severe nausea and vomiting.

They had more than double the risk of venous thromboembolism, when a blood clot forms inside a vein, and a 42 per cent higher risk of pre-eclampsia, a pregnancy complication involving high blood pressure.

Dr Steven Wambua, research fellow in health data science at King’s College London and joint first author, said: “Maternity care is still largely organised around single health conditions, but one in five women now enters pregnancy with two or more.

“By harmonising five datasets covering all four UK nations, we could show consistently and across a much broader range of outcomes than before, that these women face higher risks and that risk climbs with every additional condition.”

Researchers from King’s College London, Queen’s University Belfast, Bristol NHS Foundation Trust, the University of Birmingham, Swansea University and the University of St Andrews analysed more than 2.2m pregnancies and birth events recorded between 2000 and 2022.

The data came from five datasets covering England, Scotland, Wales and Northern Ireland.

Around one in five pregnant women in the UK live with multiple long-term conditions, but their combined impact on pregnancy is poorly understood.

The study found risks rose with each additional condition. Women with three or more conditions had more than three-and-a-half times the risk of venous thromboembolism compared with women without long-term health conditions.

Women with multiple conditions also had a 32 per cent higher risk of placental abruption, when the placenta separates from the womb before birth, and a 26 per cent higher risk of gestational diabetes.

The researchers said maternity care pathways vary considerably and, where they exist, are often organised around individual conditions.

They said the findings highlight a need to restructure these pathways to address the complex needs of women living with multiple conditions.

Professor Krishnarajah Nirantharakumar, clinical professor of public health and health data science at King’s College London, MuM-PreDiCT principal investigator and joint senior author, said: “These findings make a strong case for recognising multiple long-term conditions as a marker of antenatal risk in its own right.

“That means identifying these women at maternity booking, assessing physical and mental health needs together, and joining up obstetric, primary care and mental health services around them.

“The near four-fold risk of antenatal anxiety and depression is particularly striking, and points to perinatal mental health support as an urgent priority.

Dr Kelly-Ann Eastwood of Bristol NHS Foundation Trust and Queen’s University Belfast, joint senior author, added: “Our results help define the urgent clinical challenges facing both women entering pregnancy with multiple long-term conditions, and clinicians caring for them across the UK.

“Supporting recommendations from recent national maternity and neonatal investigation reports, there is a critical need to address healthcare inequalities, and improve support for women with pre-existing mental health conditions.

“These findings highlight the pressing need to restructure existing maternity services to improve antenatal outcomes.

The authors cautioned that, because the study used routinely collected health records, some conditions and outcomes may have been under-recorded or recorded inconsistently.

Further work by the MuM-PReDiCT consortium will examine birth and child outcomes and identify which combinations of long-term conditions carry the greatest risk.