• Sign Up

Premenstrual Syndrome


Premenstrual Syndrome

Article Author:
Pratyusha Gudipally
Article Editor:
Gyanendra Sharma
Updated:
7/21/2020 9:00:00 PM
For CME on this topic:
Premenstrual Syndrome CME
PubMed Link:
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. 


References

[1] Yesildere Saglam H,Orsal O, Effect of exercise on premenstrual symptoms: A systematic review. Complementary therapies in medicine. 2020 Jan;     [PubMed PMID: 31987230]
[2] Frey Nascimento A,Gaab J,Kirsch I,Kossowsky J,Meyer A,Locher C, Open-label placebo treatment of women with premenstrual syndrome: study protocol of a randomised controlled trial. BMJ open. 2020 Feb 17;     [PubMed PMID: 32071176]
[3] Bhuvaneswari K,Rabindran P,Bharadwaj B, Prevalence of premenstrual syndrome and its impact on quality of life among selected college students in Puducherry. The National medical journal of India. 2019 Jan-Feb;     [PubMed PMID: 31823933]
[4] Bu L,Lai Y,Deng Y,Xiong C,Li F,Li L,Suzuki K,Ma S,Liu C, Negative Mood Is Associated with Diet and Dietary Antioxidants in University Students During the Menstrual Cycle: A Cross-Sectional Study from Guangzhou, China. Antioxidants (Basel, Switzerland). 2019 Dec 26;     [PubMed PMID: 31888014]
[5] Fatemi M,Allahdadian M,Bahadorani M, Comparison of serum level of some trace elements and vitamin D between patients with premenstrual syndrome and normal controls: A cross-sectional study. International journal of reproductive biomedicine (Yazd, Iran). 2019 Sep;     [PubMed PMID: 31646259]
[6] Goker A,Artunc-Ulkumen B,Aktenk F,Ikiz N, Premenstrual syndrome in Turkish medical students and their quality of life. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2015 Apr;     [PubMed PMID: 25140580]
[7] Yamamoto K,Okazaki A,Sakamoto Y,Funatsu M, The relationship between premenstrual symptoms, menstrual pain, irregular menstrual cycles, and psychosocial stress among Japanese college students. Journal of physiological anthropology. 2009;     [PubMed PMID: 19483374]
[8] Cheng SH,Shih CC,Yang YK,Chen KT,Chang YH,Yang YC, Factors associated with premenstrual syndrome - a survey of new female university students. The Kaohsiung journal of medical sciences. 2013 Feb;     [PubMed PMID: 23347812]
[9] Abdelmoty HI,Youssef MA,Abdallah S,Abdel-Malak K,Hashish NM,Samir D,Abdelbar M,Hosni AN,Abd-El Ghafar M,Khamis Y,Seleem M, Menstrual patterns and disorders among secondary school adolescents in Egypt. A cross-sectional survey. BMC women's health. 2015 Sep 4;     [PubMed PMID: 26341264]
[10] Ansong E,Arhin SK,Cai Y,Xu X,Wu X, Menstrual characteristics, disorders and associated risk factors among female international students in Zhejiang Province, China: a cross-sectional survey. BMC women's health. 2019 Feb 18;     [PubMed PMID: 30777053]
[11] Tolossa FW,Bekele ML, Prevalence, impacts and medical managements of premenstrual syndrome among female students: cross-sectional study in College of Health Sciences, Mekelle University, Mekelle, northern Ethiopia. BMC women's health. 2014 Mar 29;     [PubMed PMID: 24678964]
[12] Tan DA,Haththotuwa R,Fraser IS, Cultural aspects and mythologies surrounding menstruation and abnormal uterine bleeding. Best practice     [PubMed PMID: 27863914]
[13] Vaghela N,Mishra D,Sheth M,Dani VB, To compare the effects of aerobic exercise and yoga on Premenstrual syndrome. Journal of education and health promotion. 2019;     [PubMed PMID: 31867375]
[14] Ryu A,Kim TH, Premenstrual syndrome: A mini review. Maturitas. 2015 Dec;     [PubMed PMID: 26351143]
[15] Fernández MDM,Saulyte J,Inskip HM,Takkouche B, Premenstrual syndrome and alcohol consumption: a systematic review and meta-analysis. BMJ open. 2018 Apr 16;     [PubMed PMID: 29661913]
[16] Dickerson LM,Mazyck PJ,Hunter MH, Premenstrual syndrome. American family physician. 2003 Apr 15;     [PubMed PMID: 12725453]
[17] Stute P,Bodmer C,Ehlert U,Eltbogen R,Ging A,Streuli I,von Wolff M, Interdisciplinary consensus on management of premenstrual disorders in Switzerland. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2017 May;     [PubMed PMID: 28277114]
[18] Lustyk MK,Gerrish WG,Shaver S,Keys SL, Cognitive-behavioral therapy for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Archives of women's mental health. 2009 Apr;     [PubMed PMID: 19247573]
[19] Girman A,Lee R,Kligler B, An integrative medicine approach to premenstrual syndrome. American journal of obstetrics and gynecology. 2003 May;     [PubMed PMID: 12748452]
[20] Fu Y,Mi W,Li L,Zhang H,Wang J,Cheng W,Sun L,Li L,Xie S,Zhang J, [Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric disorder: a randomized, double blind placebo-controlled study]. Zhonghua fu chan ke za zhi. 2014 Jul     [PubMed PMID: 25327732]
[21] Marjoribanks J,Brown J,O'Brien PM,Wyatt K, Selective serotonin reuptake inhibitors for premenstrual syndrome. The Cochrane database of systematic reviews. 2013 Jun 7;     [PubMed PMID: 23744611]
[22] Kwan I,Onwude JL, Premenstrual syndrome. BMJ clinical evidence. 2015 Aug 25;     [PubMed PMID: 26303988]
[23] İlhan G,Verit Atmaca FV,Kurek Eken M,Akyol H, Premenstrual Syndrome Is Associated With a Higher Frequency of Female Sexual Difficulty and Sexual Distress. Journal of sex     [PubMed PMID: 28287918]
[24] Owens SA,Eisenlohr-Moul T, Suicide Risk and the Menstrual Cycle: a Review of Candidate RDoC Mechanisms. Current psychiatry reports. 2018 Oct 6;     [PubMed PMID: 30293097]
[25] Chai N,Wu Y,Zhang M,Wu WB,Zhang H,Kong FW,Zhang Y, Remote intervention using smartphone for rural women suffering from premenstrual syndrome: A propensity score matched analysis. Medicine. 2018 Jul;     [PubMed PMID: 30024566]