Premenstrual syndrome

Synonyms: PMS, premenstrual disorders (PMD), premenstrual tension (PMT), premenstrual dysphoric disorder (PMDD), late luteal phase dysphoric disorder (LLPDD)

What is premenstrual syndrome?¹

Premenstrual syndrome (PMS) comprises a range of distressing physical, psychological and behavioural symptoms experienced by many premenopausal women during the luteal phase of their menstrual cycle, in the absence of organic or underlying psychiatric disease, and which disappears or significantly regresses by the end of menstruation".²

The key characteristic is the timing of the symptoms; by definition, there will be a clear symptom-free interval at some time between the end of menstruation and the estimated time of ovulation.³

Common symptoms include anxiety, irritability, depression, mood swings, sleep disorders, fatigue, altered interest in sex, breast tenderness, weight gain, headaches, change in appetite, general aches and pain and feeling bloated.

Premenstrual dysphoric disorder (PMDD), a severe subtype of PMS, has been defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as occurring when a woman suffers from at least five distinct psychological premenstrual symptoms.

PMS is distinguished from normal psychological and physical symptoms experienced by the majority of women premenstrually, by the severity of the distress they cause and the negative effect they have on daily life. Severe PMS is referred to as premenstrual dysphoric disorder (PMDD) and PMD encompasses both PMS and PMDD.

It has been proposed that PMD be classified into 'Core PMD' and 'Variants of PMD', such as significant premenstrual exacerbation of an underlying disorder or symptoms due to exogenous progestogen administration - for example, that found in hormone replacement therapy (HRT).³

Premenstrual syndrome aetiology

As symptoms come and go in line with the menstrual cycle, it has long been thought that sex steroid hormonal changes were responsible for PMS. To fit with this theory, symptoms tend to be absent during non-ovulatory cycles, abolished by oophorectomy or treatment with ovulation inhibitors, and return with administration of exogenous hormones.⁴ However, the mechanism by which the changing hormone levels cause PMS symptoms is still elusive.

An alternative theory involves sex steroids and their effect on serotonin within the brain. Animal modelling has shown that serotonin may have a role modifying the effects of sex steroid-driven behaviour such as aggression and mood. In this theory, serotonin deficiency would create excessive swings in those behaviours. Also within this model, somatic symptoms such as breast tenderness and bloating represent a lack of willingness to tolerate these (normal) changes whilst being in a dysphoric state.

It has been suggested that PMS may confer an evolutionary advantage by increasing the chances of an infertile couple breaking up, thus improving the reproductive chances of the woman in such partnerships.⁵

How common is premenstrual syndrome? (Epidemiology)

Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms occur in about 5% of those women.⁶

There is a 1.8-5.8% 12-month prevalence of premenstrual dysphoric disorder among menstruating women.⁷

Risk factors⁸

The strongest risk factor for premenstrual syndrome (PMS) is the presence of ovulatory menstrual cycles. Other possible risk factors include:

• Family history of PMS.

• Mood disorders. PMS or premenstrual dysphoric disorder (PMDD) may be a precursor to major depression, or follow a diagnosis of depression.

• Cigarette smoking.

• Alcohol intake.

• Sexual abuse and/or trauma.

• Weight gain.

• Stress.

Premenstrual syndrome symptoms

Symptoms vary between cycles; they tend to worsen markedly about six days prior to menses and peak at two days beforehand and there is always a symptom-free time in the cycle, usually after starting the period. The main symptoms leading to a consultation are irritability and inability to cope with domestic or workplace demands.

• Physical symptoms usually lead to a consultation only when mastalgia, dysmenorrhoea or migraine have not responded to self-management.

• Difficult interpersonal relationships with a spouse or children may also precipitate a consultation. The risk of perimenopausal and postnatal depression as well as anxiety disorders, appears to be higher amongst women with PMD.⁴

• Psychosexual problems, loss of libido and dyspareunia may be reported but usually have to be specifically asked about.

There are no specific signs of the syndrome, so the problem is best delineated on the basis of a history and symptom diary kept over 2-3 months. There may be leg or breast oedema.

The clinician should be particularly careful not to accept without question parent-reported diagnosis of PMS in adolescent girls who may have more serious underlying psychological illness.

Differential diagnosis

This includes psychological conditions worsened by PMS. Depending on individual presentation, differential diagnoses which may need to be considered include:⁸

• Depression.

• Anxiety and panic disorders.

• Hypothyroidism.

• Anaemia, including iron deficiency anaemia, B12 deficiency anaemia and folate deficiency anaemia.

• Dysmenorrhoea.

• Irritable bowel syndrome.

• Interstitial cystitis.

• Endometriosis.

• Chronic fatigue syndrome.

• Fibromyalgia.

• Systemic lupus erythematosus.

Investigations

Ask the patient to keep a symptom diary over two complete cycles, to help with diagnosis. Later this will also help to assess effectiveness of any interventions.

• Check blood pressure and pulse rate.

• Consider breast and thyroid examination, as appropriate.

• Consider pelvic examination, particularly if bloating is a major problem (this may be ascites due to alternative ovarian pathology), or other reason to suspect a physical cause of abdominal swelling.

There are no useful tests to confirm the diagnosis. Consider other blood tests only if there is reason to suspect an alternative physical cause for symptoms.

Premenstrual syndrome treatment and management^{8 9}

Management should be tailored to the severity and type of symptoms, the woman's treatment preferences, and any desire to become pregnant. Explanation, reassurance and support may be all that are required.

Severity is usually based on clinical judgement after considering the woman's perception of symptom severity, the impact of symptoms on the woman's quality of life, and the presence or absence of distress or impairment of socioeconomic function.

Advice for all women with premenstrual syndrome

• Offer lifestyle advice that includes:

  • Regular, frequent (2-3 hourly), small, balanced meals rich in complex carbohydrates.

  • Regular exercise.

  • Regular sleep.

  • Stress reduction.

  • Smoking cessation.

  • Alcohol restriction.

• Support stockings to help aching legs.

• If the predominant symptom is pain (for example, headache or generalised aches and pains), prescribe a simple analgesic, such as paracetamol or a non-steroidal anti-inflammatory drug (NSAID).

• Use of a firm, supportive bra. See also the article on Breast Pain.

• The limited evidence available suggests that acupuncture and acupressure may improve both physical and psychological symptoms of PMS when compared to a sham control.¹⁰

• There is otherwise only limited evidence to support the use of complementary treatments and dietary supplements, including reflexology, calcium and vitamin D, ginkgo biloba, evening primrose oil, vitamin B6, and magnesium.

For women with moderate PMS symptoms

• New-generation combined oral contraceptive (COC), especially if contraception also required.

• Referral for cognitive behavioural therapy (CBT) if potential benefit from psychological intervention.

For women with severe PMS

• Consider selective serotonin reuptake inhibitor (SSRI) continuously or just during the luteal phase (eg, days 15-28 of cycle, depending on cycle length).

• Arrange referral for CBT if considered to be potentially beneficial.

Review and referral

• Review after two months to assess the effectiveness of the treatment. Effectiveness should be established using a validated symptom diary, such as the Daily Record of Severity of Problems (DRSP) questionnaire.

• If no improvement, consider other conditions that could explain the symptoms - eg, depression, hypothyroidism, anaemia, irritable bowel syndrome, and endometriosis.

• If there are no underlying conditions and primary care management is not adequately effective, consider referral to a clinic with a specific interest in PMS (general gynaecology clinic if not available) for further assessment and management.

Pharmacological

Many treatments have been put forward but few have supportive evidence to justify their use. Treatment needs to be tailored to the severity of the PMS. Try simple analgesia, as required, for breast tenderness, headaches and period pains. Pharmacological options fall into two broad categories: those that affect brain neurotransmitters, particularly serotonin, and those that interfere with ovulation.

• Psychotropics - selective serotonin reuptake inhibitors (SSRIs):

  • SSRIs are first-line for women over 18 years of age with severe PMS. They have been shown to be effective in many trials, with 60-90% of women showing improvement with active treatment versus 30-40% for placebo treatments.¹¹

  • SSRIs reduce both mood symptoms and somatic complaints and can be prescribed in primary care for women who predominantly have mood symptoms. This is an off-label use and the woman should be told this.

  • The short onset of action enables limiting their use to the symptomatic luteal phase of the menstrual cycle, typically starting 14 days before menstruation is expected and continuing until bleeding starts.

  • They may be effective taken 'as required' but there is currently limited evidence for this strategy.¹²

• Suppression of ovulation

  • Combined hormonal contraceptives (CHCs) are commonly thought to improve symptoms but there are few good trial data to support their use. Drospirenone plus 20 mg estradiol may help reduce PMS symptoms but a Cochrane review concluded that any superiority over other CHCs was unclear.¹³ Taking a CHC continuously for three cycles may reduce PMS symptoms and may be an option for women who want to use CHCs for contraception.¹⁴

  • Transdermal oestrogen is one of the more effective treatments for PMS symptoms. It should be given as a transdermal patch, gel or subcutaneous implant, as oral oestrogen is usually insufficient to suppress ovulation; 100, 150, or 200 micrograms may be necessary. If the woman has an intact uterus she will need to be given a progestogen to prevent endometrial hyperplasia. A levonorgestrel-containing intrauterine system (IUS-LNG) delivers this without causing symptoms to return.²

  • Use of gonadotrophin-releasing hormone (GnRH) analogues with HRT add-back therapy achieves ovulation inhibition whilst also providing uterine protection. No particular form of HRT appears to be better than any other. Response rate is reported to be between 60-75%.¹² Women having long-term ovulation inhibition (> 6 months) should have annual DEXA scans whilst on treatment.

  • Danazol, although effective in reducing premenstrual breast pain, is rarely used now due to the risk of masculinisation and other side-effects.¹²

  • Progestogen alone is not recommended for women with PMS, due to insufficient evidence to support its effectiveness.¹⁵

Surgery

In women with severe PMS symptoms, surgery (hysterectomy or bilateral salpingo-oophorectomy) may be considered in secondary care.⁸

Prognosis

Most women can find effective solutions to their symptoms. A small number of women continue to be affected severely with worsening symptoms until the menopause.⁸