Continuing Education Activity

This activity is a review of the existing literature on premenstrual syndrome (PMS). It summarizes the management of PMS by outlining the importance of taking a comprehensive history and performing a detailed physical examination and makes a note of necessary diagnostic tests to be done to rule out other conditions that may present with similar symptoms. Moreover, it describes the role of the interprofessional team in the diagnosis and providing the best possible care for the patient.

Objectives:

• Outline the spectrum of symptoms associated with premenstrual syndrome.
• Describes the pathophysiology of the symptoms in premenstrual syndrome.
• Reviews the management of premenstrual syndrome.

Introduction

Premenstrual syndrome (PMS) encompasses clinically significant somatic and psychological manifestations during the luteal phase of the menstrual cycle, leading to substantial distress and impairment in functional capacity. These symptoms disappear within a few days of the onset of menstruation.[1] The pooled prevalence of reproductive age women affected with PMS worldwide amounts to 47.8%.[2] Among these, about 20% of women experience symptoms severe enough to disrupt their daily activities, and the remaining have mild to moderate symptoms. Symptoms of PMS include changes in appetite, weight gain, abdominal pain, back pain, low back pain, headache, swelling and tenderness of the breasts, nausea, constipation, anxiety, irritability, anger, fatigue, restlessness, mood swings and crying.[1]

The premenstrual dysphoric disorder (PMDD) is a more severe form of the same, which has been included as a psychiatric disorder in the fifth edition of the diagnostic and statistical manual for mental disorders (DSM-5).[3] Many nonpharmacological and pharmacological treatment methods are used to alleviate these symptoms. Nonpharmacological therapies are the first line of management for mild symptoms, and those with severe symptoms are treated with pharmacological therapy, mainly the selective serotonin reuptake inhibitors (SSRIs).[3] The various nonpharmacological therapies used to treat mild symptoms include physical activity and exercise, nutrition, herbal preparations, cognitive behavioral therapy and social support, adequate rest, regular hot baths, and vitamin supplements.[1]

Etiology

The etiology of premenstrual syndrome is uncertain. Since PMS symptoms occur simultaneously with the hormonal fluctuations of the menstrual cycle, hormonal disproportion like estrogen surplus and progesterone deficiency have been proposed. Symptoms are also associated with serotonin to link as a key etiological factor.

Estrogen comprises of three major hormones: estrone, estradiol, estriol, estradiol being the is the most potent. Estrogen levels that fluctuate during the luteal phase are what is responsible for women’s mood changes. Clinical trials have shown that serotonin precursors significantly increases between days 7 to 11 and 17 to 19 of the menstrual cycle. This indicates that PMS is closely associated with mood disorders through estrogen-serotonin regulation.

According to the molecular biology studies, the decreased estrogen causes the hypothalamus to release norepinephrine, which triggers a decline in acetylcholine, dopamine, and serotonin that leads to insomnia, fatigue, depression, which are common symptoms of PMDD and PMS.[4]

A study from Egypt revealed the positive association between PMS and excess intake of sweet-tasting food items. It also showed that other factors, such as intake of junk food and coffee, were significantly associated with PMS. Thus, making it evident that lifestyle factors have a significant association with PMS and PMDD.[3] Cheng et al. did a similar study among women university students for assessing the factors associated with PMS and revealed that dietary factors such as consumption of fast food, drinks containing sugar, deep-fried foods, and lifestyle factors such as less habitual exercise and poor sleep quality is significantly associated with PMS.[3]

Epidemiology

Epidemiological studies have revealed that about 80% to 90% of women manifest at least one of the PMS signs; however, in about 2.5% to 3% of women, the syndrome severe enough to affect their activities and social communications. This disorder is known as premenstrual dysphoric disorder (PMDD).[5]

Female university students are affected the most by PMS. The rate of PMS is believed to be high among this population, and it adversely affects their life and academic performance. The prevalence of PMS among the university students of different countries are as follows; for example, 33.82% in China, 37% in Ethiopia, 39.9% in Taiwan, 65% in Egypt, 72.1% to 91.8% in Turkey, and 79% in Japan.[6][7][8][9]

This geographical difference in the prevalence of PMS may be attributed to disparities in genetic, dietary, and lifestyle factors among young adult females and also may be attributable to various community-adopted practices before and during menstruation.[10][11][12]

Pathophysiology

The pathophysiology of premenstrual syndrome is complex, imprecise, and is not fully understood.

• It is anticipated that PMS is likely to be influenced by the action of progesterone on neurotransmitters like gamma-aminobutyric acid (GABA), opioids, serotonin, and catecholamine. Preexisting serotonin deficiency with increased progesterone sensitivity is also considered responsible for this disorder.
• An increase in prolactin levels or an increase in its sensitivity to the effect of prolactin, glucose metabolism alterations, abnormal hypothalamic–pituitary–adrenal (HPA) axis function, insulin resistance, and certain nutritional electrolyte deficiencies, and genetic factors have a role in PMS.
• Stress amplifies the sympathetic activity, and this results in menstrual pain by significantly increasing the intensity of uterine contraction.[13]

History and Physical

Symptoms of premenstrual syndrome can range from mild to moderate to severe. These symptoms may include changes in appetite, weight gain, abdominal pain, back pain, low back pain, headache, swelling and tenderness in the breasts, nausea, constipation, anxiety, irritability, anger, fatigue, restlessness, mood swings and crying.[1] 

The duration of affective symptoms can vary from a few days to 2 weeks. Symptoms often worsen a week before and spike two days before menstruation begins.[14] Alcohol drinking is associated with a moderate increase in the risk of PMS.[15] As such, documenting the history of alcohol consumption can help provide counseling to the patient and help alleviate the symptoms accordingly.

Evaluation

To establish a diagnosis of PMS and PMDD, a variety of other disorders, both physical and psychiatric, needs to be excluded. The three elements that confirm the diagnosis are (1) symptoms being consistent with PMS, (2) the symptoms should occur consistently only during the luteal phase of the menstrual cycle, and (3) negative impact on the patient's function and lifestyle. Once the physician is highly suspicious of the diagnosis, patients should be advised to keep a diary for premenstrual symptoms for consecutive months to assess for cycle-to-cycle variability.[16]

An initial workup for diagnosis could also include ruling out other pathologies like thyroid disorders, Cushing syndrome, and hyperprolactinemia, as such ordering follicle-stimulating hormone (FSH), estradiol (E2), thyroid-stimulating hormone (TSH), prolactin, and cortisol should be done.[17]

Treatment / Management

The main intention to treat PMS is symptom relief and to reduce its effects on daily routine activities. Pharmacotherapy was always the first line of treatment for premenstrual syndrome, but recent research has suggested the superior benefits with combination therapy.

Combination of pharmacotherapies (such as NSAIDs, SSRIs, anxiolytic agents, gonadotropin-releasing hormone (GnRH) agonists, spironolactone, oral contraceptive pills) with nonpharmacological treatments, mainly cognitive and behavioral therapies, exercises, massage therapy, light therapy along with dietary and nutritional modifications have been proven beneficial for the treatment of premenstrual symptoms.[13]

Lifestyle modifications include regular exercise, avoiding stressful events, and maintaining healthy sleeping habits, especially during the premenstrual period. Increased intake of complex carbohydrates increases the level of tryptophan, a serotonin precursor.[14]

Cognitive-behavioral therapy (CBT) is an approach that emphasizes the correction of unsettled disruptive thoughts, behaviors, and emotions. CBT helps in the recognition of these behaviors and helps develop coping strategies to improve daily functioning.[18]

The fruit extract Vitex agnus-castus is the only herbal medicine that is proven to control PMS-associated mood swings and irritability.[19]

Recent studies of combined oral contraceptives comprising 0.02 mg of ethinyl estradiol and 3 mg of drospirenone (compound hormone pills for 24 days followed by hormone-inactive pills for the last four days) have demonstrated an improvement in PMDD symptoms.[20]

Selective serotonin receptor inhibitors (SSRIs) can be used as the first-line treatment of PMS with predominantly emotional symptoms.[21]

Differential Diagnosis

Several clinical entities can have a manifestation similar to premenstrual syndrome. They include psychiatric conditions like substance abuse disorders, affective disorder (e.g., depression, anxiety, dysthymia, panic), anemia, anorexia and bulimia, gynecological conditions like endometriosis, dysmenorrhea, medical conditions like hypothyroidism and others like oral contraceptive pill (OCP) use, or perimenopause. hence it is essential to gather an effective history and perform a comprehensive physical examination and rule out these conditions.[16]

Prognosis

Symptoms of PMS can mostly recur after stopping the treatment, except after oophorectomy and menopause.[22]

Complications

Untreated PMS are likely to affect sexual life, thereby leading to a higher level of sexual distress, which can, in turn, lead to relationship problems and more psychological issues.[23] There is also evidence that relates the PMS to increased suicidal risk in hormone-sensitive females.[24]

Deterrence and Patient Education

Premenstrual syndrome is a common problem among females of childbearing age. Patient education involves discussing the problem with the patient with empathic hearing, providing insight on the reasons for her problems. The involvement of the partner in understanding the problem also assists the patient in seeking help at home or seek treatment with the health care provider.

Educating patients about reproductive health helps the patient-physician relationship, which makes symptom expression and treatment-seeking easier. Equally important is educating significant others and family members about supportive behaviors, which reduces PMS symptoms. Couple-based CBT interventions have a great impact on behavioral coping with better outcomes. Because it is a common problem, mass education through radio, TV, or digital platforms regarding diagnosis and effective treatment of PMS is very helpful too.[25]

Enhancing Healthcare Team Outcomes

The diagnosis of PMS is challenging due to the lack of explicit signs on physical examination and lack of diagnostic testing. Hence it requires the involvement of the patient, nurses, and physician to make a diagnosis. The role of the patients can include maintaining a diary which elaborates their symptoms and yield in early diagnosis whereas the nurses can be extremely helpful if they help in collecting a filled-in questionnaire from the patients during the monthly visit. Physicians on the other hand can use these tools in excluding other differentials which may produce better outcomes.