Pre-menstrual Dysphoric Disorder: A Review

Abstract

Abstract

Introduction: Premenstrual dysphoric disorder (PMDD) is a distressing disorder amongst women of reproductive age group with significant implication in the productivity and quality of life of women who suffer from it. It is generally neglected as it is mostly undifferentiated from premenstrual symptoms—milder presentation of the same spectrum of problem but of lesser intensity and impairment.

Objective: Here, in this article, we aim to highlight various studies and the research done on PMDD in the context of Indian women.

Method: Reviewing the last 40 years’ database including Medline (PUBMED), Cochrane Library, EMBASE, Trip, Psych INFO, CINAHL, the Allied and Complementary Medicine Database (AMED), and the British Nursing Index.

Results: PMDD is a troublesome disorder, often underdiagnosed. A thorough history including menstrual and sexual history, conducting a thorough physical examination, assessing the comorbidities, and finally using a proper and structured treatment protocol for managing the condition are recommended. Sertraline is the most widely studied drug which is found to be effective in PMDD.

Introduction

Premenstrual dysphoric disorder (PMDD) is a very distressing disorder among child-bearing females. It is generally neglected and undifferentiated from premenstrual syndrome (PMS).^1,2 It is commonly named as premenstrual tension/premenstrual syndrome/late luteal phase dysphoric disorder/premenstrual tension syndrome (International Classification of Diseases, Tenth Revision) or PMDD (Diagnostic and Statistical Manual of Mental Disorders, fifth edition).^3,4 In ICD-11, it is now out of the appendix. ⁵ The American College of Obstetricians and Gynecologists also defines PMDD similarly. ⁶ The prevalence of PMDD is 3% to 9%. ⁷ Similar numbers have been reported from India across various states.^8–13

Etiology

Currently, there is no consensus on the cause of PMDD. Biologic, genetic, psychological, environmental and social factors all seem to play a very important role.

Genetic Vulnerabilities

The role of the gene coding for serotonergic 5HT 1A receptor^14–18 and estrogen receptor alpha gene (ESR 1) has been documented. ¹⁹

Various risk factors such as high body mass index, stress and experience of traumatic events play role in the etiology of PMDD.^20–23

The Role of Sex Steroids and Their Metabolites

Changes in serotonin and γ-aminobutyric acid (GABA) levels with estrogen and progesterone metabolites have interaction with the GABA-A receptor complex in neurobiology of PMDD.^24–30 Studies report that administration of progesterone/allopregnenolone during the follicular phase enhances amygdala reactivity.^31,32

Other hormones such as thyroid hormone, melatonin, cortisol and relaxin^33–39 also have been implicated in the pathophysiology of PMDD.

Calcium, magnesium, insulin-like growth factor 1 and vitamin D^40–44 have been hypothesized to be responsible for causing various somatic symptoms of PMDD.

Neurotransmitters Implicated in PMS/PMDD

Experiments on animals demonstrate that serotonin depletion causes enhanced aggression and sexual activity.^45–47 GABA causes tolerance induction and withdrawal effects in such women. ³⁰ Low levels of glutamate/creatine plus phosphocreatine in luteal phase in the medial prefrontal cortex have also been studied. ³² Decreased levels of endogenous opioids are responsible for increased pain sensitivity.^48,49 In animal studies, an increased startle response is found due to progesterone withdrawal^50–52 and up regulation of the alpha-4 unit of the GABA-A receptor complex. ⁵¹

Somatic Symptom Pathophysiology

Prolactin-lowering agents, such as the dopamine D2 receptor agonist bromocriptine,^53,54 chasteberry ⁵⁵ administration of danazol in luteal phase, and estrogen receptor antagonists^56,57 all are effective in mastalgia.

Aldosterone, a progesterone metabolite58 and deoxycorticosterone, an aldosterone agonist^24,58 have a role in treatment of severe abdominal bloating.

Other common somatic complaints such as premenstrual headache, migraine, and epilepsy are comorbid with PMDD and endometriosis. ⁵⁹

Classification of PMS

Royal College of Obstetricians and Gynaecologists classifies PMS into four variants ⁶⁰ :

‘Premenstrual exacerbation of an underlying disorder’, such as diabetes, depression, epilepsy, asthma, and migraine.

‘Non-ovulatory PMDs’ occur in the presence of ovarian activity without ovulation.

‘Progestogen-induced PMDs’ are caused by exogenous progestogens present in hormone replacement therapy and the combined oral contraceptive pill.

‘PMDs with absent menstruation’ include women who still have a functioning ovarian cycle, but for reasons such as hysterectomy, endometrial ablation or the levonorgestrel-releasing intrauterine system, they do not menstruate. ⁶¹

National Association for Premenstrual Syndrome subdivide PMS into mild, moderate, and severe. ⁶²

Clinical Features

Symptoms in PMDD include anxiety, depression, irritability, anger, bloating, muscle pain, poor concentration, etc., causing severe distress that is persistent in several cycles, characteristically appearing one week before periods and disappearing within first two days of bleeding. ⁶³ Women with PMDD usually have comorbid physical and psychiatric disorders, and one must always keep these comorbidities as dual diagnosis whenever in doubt.^64–72

Management

Thorough investigations for comorbidities must always be done. Among psychological tools, the premenstrual symptoms screening tool was developed at McMaster University in 2003 and a new Japanese scale was made in 2009.^73,74 There is a scale currently validated for the Indian population as well.

In psychopharmacological treatment, the British Journal of Obstetricians and Gynecologists protocol emphasizes the use of fluoxetine and sertraline in the treatment of PMDD.^60,75 The hormonal therapies recommended by the British Journal of Obstetricians and Gynecologists include leuprolide depot, leuprolide depot with ovarian hormone supplements, goserelin with estrogen supplementation, danazol, oral contraceptive pills, progesterone-only drugs, estradiol patches, spironolactone, bromocriptine, Ibuprofen, etc.^14,60

In non-pharmacological treatment, lifestyle changes including regular, frequent, small balanced meals rich in complex carbohydrates and low in salt, fat, and caffeine, regular exercise, smoking cessation, alcohol restriction, regular sleep, and maintaining PMDD charts have been found to be helpful. Nutritional supplements including vitamin B6, up to 100 mg per day, vitamin E, up to 600 IU per day, calcium carbonate, 1200 to 1600 mg per day, magnesium, up to 500 mg per day, tryptophan, up to 6 g per day have been suggested.

Others therapies with some benefit include stress reduction and management, anger management, self-help support group, individual and couples therapy, cognitive behavioral therapy, music therapy, light therapy with 10,000 lux cool white fluorescent light, etc.^14,20,60

Conclusion

PMDD is prevalent mental health condition affecting mental and physical well-being of women and yet is underdiagnosed. Careful history and examination regarding PMDD should be a norm in every woman patient presenting to a psychiatrist. Management consists of pharmacological and non-pharmacological intervention with variable prognosis.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.