Premenstrual dysphoric disorder: recognition, management and treatment

Introduction

Premenstrual dysphoric disorder (PMDD) is an under-recognised cyclical mood disorder affecting women and anyone with a womb or ovaries during their reproductive years. In PMDD, affective, physical and cognitive symptoms occur in the second half of the menstrual cycle (i.e. luteal phase) and tend to resolve after menstruation^​1​. This is owing to the affected individuals being unusually sensitive to the normal fluctuations of hormones that occur during the menstrual cycle. In the UK, approximately 824,000 females have PMDD, which is around 1 in 20 women^​2​. The prevalence of PMDD globally is thought to be between 2–5%; however, this is likely to be an underestimation of the lifetime prevalence of PMDD^​3​.

Common affective symptoms include, but are not limited to: depression, dysphoria, labile mood, anger, irritability, anxiety, rejection sensitivity, feelings of worthlessness and suicidal ideation^​1,4​. In the UK, approximately 593,600 individuals with PMDD will experience suicidal ideation, 412,000 will self-harm and 275,000 will attempt suicide in their lifetime^​2​. Common cognitive symptoms include memory impairment, forgetfulness, brain fog and executive dysfunction^​4​. 

PMDD can have a significant impact on daily functioning, relationships and overall quality of life, which is similar to other psychiatric conditions^​4,5​. The impact on interpersonal relationships can also be profound, and the resulting conflict can further exacerbate symptoms^​4​. PMDD is also associated with increased absence from workplaces or educational institutions, reduced productivity and motivation, reduced school performance and social withdrawal^​4​. 

As PMDD is an under-recognised condition, there is a lack of education on the disorder and a lack of awareness among healthcare professionals^​1​. This contributes to a significant delay in receiving a diagnosis, which on average is around 12 years^​1,6​. Symptoms of PMDD overlap with other psychiatric conditions — most commonly major depressive disorder, emotional unstable personality disorder (EUPD, previously known as borderline personality disorder), anxiety disorders and bipolar affective disorder — further contributing to the delay in diagnosis^​7,8​. 

PMDD symptoms can also overlap with those of physical health conditions, such as fibromyalgia, chronic fatigue, autoimmune disorders and thyroid dysfunction^​7​. The difference between these conditions and PMDD is that with PMDD, the symptoms are distinctively cyclical and will only appear during the luteal phase of the menstrual cycle and disappear upon the onset of menstruation or a few days thereafter. With the physical conditions mentioned, some people may experience premenstrual exacerbation (PME) of their conditions (mental and physical); however, these symptoms are still ongoing throughout their cycle and don’t disappear after the luteal phase ends^​9​.

The prevalence of PMDD may partly be underestimated and under-diagnosed because of the stigma still attached to both menstruation and mental health disorders^​10​. Symptoms, despite their severity, could be dismissed as being caused by pre-menstrual syndrome (PMS), and therefore individuals might not seek help, thinking of them as ’normal’^​10​. Research suggests that individuals with PMDD face discrimination from healthcare professionals, which decreases the likelihood of them seeking help, thus delaying both diagnosis and treatment^​11,12​.

Diagnostic criteria

The diagnostic criteria for PMDD differ slightly between the American Psychiatric Association’s Diagnostic and Statistical Manual, 5th Edition (DSM-5) and the International Classification of Diseases, 11th Revision (ICD-11; see Table 1) ^{​11–13​}.

Pathophysiology of PMDD

The menstrual cycle is categorised as having three phases: follicular phase (days 1–13), ovulation (day 14), and luteal phase (days 15–28). During these phases, there are natural fluctuations in the hormones oestrogen and progesterone to prepare the body for either pregnancy or menstruation. The aetiology of PMDD is multi-factorial, which includes genetic, biological and psychosocial factors^​14,15​. 

PMDD is an abnormal central nervous system response — at the receptor level — to normal hormonal fluctuations that occur in the luteal phase of the menstrual cycle^​16,17​. There is evidence that the change in hormonal levels is linked with a change in the levels of neuroactive steroids, such as gamma-aminobutyric acid (GABA) and neurotransmitters, such as serotonin^​17,18​. 

GABA is the primary inhibitory neurotransmitter in the brain and produces a calming and anxiolytic effect^​19​. There are two types of GAPA receptors on nerve cells: GABA-A and GABA-B^​18​. The GABA-A receptor system is influenced by progesterone and its metabolite allopregnalone, which enhances the function of GABA-A receptors^​19​. Individuals with PMDD seem to have an altered GABA-A receptor sensitivity that makes them more sensitive to the fluctuations of allopregnanolone and leads them to experience anxiety and irritability rather than the calming effects of GABA^​17​.

In addition to the core affective symptoms experienced in the luteal phase, individuals with PMDD also experience increased sensitivity to stress during the luteal phase^​19,20​. This includes a heightened subjective perceived stress and an altered physiological stress response, such as that mediated by the hypothalamic–pituitary–adrenal (HPA) axis function^​20,21​. 

The HPA axis consists of several pathways that maintain homeostasis in the context of stress, with cortisol being one of the primary hormones^​22​. The findings of a study, published in 2023, show evidence of dysregulation of the HPA axis in PMDD, including lower baseline cortisol levels and dysregulation in response to stress in both the follicular and luteal phase^​22​. Study results, published in 2024, also revealed that blunted cortisol levels are suggestive of poor flexibility of the HPA axis when dealing with acute psychosocial stress^​23​.

Other factors that make individuals more susceptible to PMDD are adverse childhood experiences and early-life trauma, which may cause dysregulation of the HPA axis. Dietary factors and vitamin deficiencies (e.g. vitamins A, C, D and E) have also been implicated as causes of dysregulation, as has alcohol consumption, smoking and being overweight^{​24–27​}. 

There is also limited but emerging research, published in 2023, that suggests a link between mast cells and histamine to the pathophysiology of PMDD, which can help explain why some individuals report cyclical exacerbations of histamine-related symptoms alongside mood dysregulation^​28​.

Table 2 shows how PMDD differs from bipolar disorder and EUPD^{​13,29–33​}.

Pharmacological management of PMDD

Selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are considered to be the first-line treatment for PMDD^​34,35​. However, they are not licensed for PMDD in the UK^​36​. SSRIs are thought to work more quickly for individuals who have PMDD than they do for people who have anxiety or depression, making it a flexible treatment approach that can be taken either continuously throughout the month or just during the luteal phase^​34,35​. This contrasts with antidepressants being taken for depression or anxiety disorders, where they should be continued for at least six months following a first episode of depression and up to two years for recurrent episodes^​37​. The findings of a study, published in 2005, found that the intermittent-dosing regimen eliminates the risk of long-term withdrawal syndrome by avoiding continuous daily use, while no short-term withdrawal symptoms have been seen^​38​. They can also reduce PMDD symptoms by improving irritability, depressed mood, mood lability, anxiety and some physical symptoms, such as bloating and breast tenderness^​34​.

Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) are also a treatment option for PMDD. Clinical trial results, published in 2001, showed venlafaxine to be more effective, but more research is required to explore the potential of luteal dosing of venlafaxine compared with SSRIs^​39​. 

Drospirenone-containing contraceptive pills

Combined oral contraceptives (COCs) contain oestrogen and progestin, which have shown efficacy in PMDD. COCs that contain 3mg drospirenone/20 mcg ethinyl estradiol are the most effective at improving both the emotional and physical symptoms of PMDD^​40​. Studies have shown dosing continuously for 24 days and having a 4-day break, rather than the typical ‘21 days on and 7 days off’ regimen, is more effective^​36,40​. Drospirenone is derived from 17a-spirolactone and its pharmacological profile is more similar to natural progesterone than other progestins^​41​. Drospirenone also blocks the action of aldosterone, increasing excretion of water and sodium, reducing water retention and other symptoms, such as breast tenderness^​42​. Other COCs may also be helpful, although not as well studied^​15​. 

In comparison to the COCs, progestin-only treatments, such as the progestin-only pill (POP), levonorgestrel IUD, etonorgestrel implant or the depot medroxyprogesterone acetate, all have the potential to affect mood symptoms of PMDD negatively, thus are not recommended^​15​. 

Copper intrauterine devices (IUDs) are recommended for those not seeking hormonal contraceptives. 

Gonadotropin-releasing hormone analogues

Gonadotropin-releasing hormone (GnRH) analogues cause a temporary ‘chemical’ menopause by preventing ovulation and production of hormones, flattening out the fluctuations that occur in the menstrual cycle and what individuals with PMDD are sensitive to^​43,44​. They should be considered as a treatment option when SSRIs and COCs have failed to manage symptoms^​45​. However, GnRH therapy does carry the risk of osteoporosis, as well as menopausal symptoms such as hot flushes and mood changes^​45​. Oestrogen and/or progesterone can be added back to the treatment to reduce the incidence of these side effects, usually via HRT, when treatment is extended beyond six months^​46​. GnRH analogues are available as both injections and tablets in the UK.

Non-pharmacological strategies

Cognitive behavioural therapy

Cognitive behavioural therapy (CBT) can help individuals manage their PMDD symptoms by supporting the development of positive coping styles and stress management, potentially improving functional and psychological impairment, as well as symptom intensity^​36,47​. However, further studies are required to demonstrate the efficacy of CBT for PMDD^​47​.

Lifestyle interventions

For PMS symptoms, guidelines consistently recommend regular, frequent two–to-three hourly, small, balanced meals that are rich in complex carbohydrates and calcium, including fruit, vegetables, wholegrain foods, lean proteins and healthy fats to help stabilise blood sugar levels, manage cravings, reduce overall inflammation and prevent mood fluctuations — particularly during the luteal phase^​36,48​. Unhealthy fats, sugar and salt should be limited, as excessive consumption can cause bloating and fluid retention^​48​. A dietician who specialises in PMDD or menstrual disorders may be best placed to support a personalised diet plan. 

Other lifestyle interventions include^​36,49​:

• Regular exercise;
• Weight management;
• Regular sleep;
• Stress reduction;
• Smoking cessation (if applicable);
• Alcohol restriction (if applicable).

Adjunctive treatments

There are other treatments for the relief of PMDD symptoms; however, these treatments are not considered to be first-line owing to the limited evidence base. They are detailed in Table 3^{​7,35,46,49–54​}.

Surgery

Surgery is considered the last resort when all other treatment options have failed^​55​. Surgery involves a hysterectomy (i.e. removal of the uterus), which makes it impossible to become pregnant or have periods afterward, and a bilateral oophorectomy (i.e. removal of both ovaries)^​55​. This is also known as a surgical menopause^​56​. It is the removal of the ovaries that induces surgical menopause as, without the ovaries, there can be no hormonal fluctuations to trigger PMDD symptoms^​56​. The type of surgery is dependent on whether progesterone add-back is tolerated in HRT — if not, both hysterectomy and bilateral oophorectomy would be recommended^​56​.

The pharmacist’s role

Pharmacists and the pharmacy team have a crucial part to play for people who have PMDD^​57​. Many individuals may turn to their pharmacist for information about how to treat their symptoms before or instead of consulting a doctor. Therefore, pharmacists are ideally placed to provide support to individuals on how to manage the physical and emotional symptoms of PMDD in several important ways^​58​:

• Early identification and screening: Pharmacists can support individuals presenting with PMDD-type symptoms by advising them to track their symptoms for at least two cycles to help with a diagnosis. They can also signpost to apps, advise keeping a diary or using the ‘Daily Record of Severity of Problems’, a gold-standard, clinically validated tool^​59​. 
• Patient education and counselling: Pharmacists can provide advice about specific lifestyle interventions, such as diet, exercise, sleep hygiene, alcohol and smoking cessation/reduction, and signpost to other resources to help manage stress, such as mindfulness and yoga^​58​.
• Pharmacological management and medication reviews: Pharmacists can counsel on evidence-based treatments (e.g. SSRIs, COCs), monitor adherence, side effects and dosing regimens, as well as advise on analgesia or supplements with supporting evidence while considering interactions^​57,58​.
• Mental health and holistic support: Pharmacists can screen for comorbid anxiety or depression and refer to CBT or other services where appropriate.
• Collaborative care: Working within multidisciplinary teams, pharmacists can liaise with GPs, escalate concerns, such as suicidal ideation, and support referral to psychiatry, gynaecology and a dietician. In primary care, they can also link patients with social prescribers and wellbeing coaches.
• Advocacy and reducing stigma: Pharmacists can help reduce stigma by normalising menstrual health discussions, offering safe spaces for patients and signposting to charities such as the International Association for Premenstrual Disorders^​1​. They can also encourage women to seek workplace support.

Conclusion

PMDD is an underdiagnosed and undertreated condition, despite its substantial impact on women’s health and society in general^​10​. Pharmacists are ideally placed to improve outcomes through early recognition, preventing delays in diagnosis, providing patient education, guiding optimal use of medicines and giving holistic support^​57,58​. By collaborating across healthcare systems and empowering women with accurate, evidence-based information, pharmacists can help bridge the treatment gap in PMDD. Pharmacy teams can also support the workforce by having more knowledge and awareness about PMDD, reducing the stigma associated with PMDD^​60​.