Ladies' Problems

NOTES

Premenstrual Mood Changes Many women in their reproductive years experience transient physical and emotional changes around the time of their period. In fact, at least 75% of women with regular menstrual cycles report unpleasant physical or psychological symptoms premenstrually. For the majority of women, these symptoms are mild and tolerable. However, for a certain group of women, these symptoms can be disabling and may cause significant disruption in their lives.

Premenstrual Syndrome (PMS) First introduced in the 1950s, the term "PMS" has been widely used by the popular press and thus has been variably defined. PMS typically refers to a general pattern of physical, emotional, and behavioral symptoms occurring 1-2 weeks before menses and remitting with the onset of menses. PMS is common, affecting from 30-80% of women of reproductive age. The most common physical symptoms include abdominal bloating, headaches, muscle and joint pain, and breast tenderness. The behavioral symptoms most commonly observed in women with PMS are fatigue, forgetfulness, poor concentration, and mild mood changes, including irritability and depressed mood.

Psychological Symptoms · Depression · Anger · Irritability · Anxiety · Sensitivity to rejection · Sense of feeling overwhelmed · Social withdrawal

Physical Symptoms · Lethargy or fatigue · Sleep disturbance (usually hypersomnia) · Appetite disturbance (usually increased) · Abdominal bloating · Breast tenderness · Headaches · Muscle aches, joint pain · Swelling of extremities

Premenstrual Dysphoric Disorder (PMDD) Premenstrual dysphoric disorder (PMDD) is a more severe form of premenstrual syndrome affecting 3-8% of women in their reproductive years. In contrast to PMS, PMDD is characterized by more significant premenstrual mood disturbance. The most common symptom is irritability; however, many women also report depressed mood, anxiety, or mood swings. These symptoms emerge one to two weeks preceding menses and resolve completely with the onset of menses. By definition, this mood disturbance results in marked social or occupational impairment, with its most prominent effects in interpersonal functioning.

PMDD is a psychiatric diagnosis and is considered to be one of the affective disorders, classified in the DSM-IV-TR as "depressive disorder not otherwise specified." PMDD can be distinguished from other affective disorders primarily by the cyclical nature of the mood disturbance. Unlike other affective disorders, mood symptoms are only present for a specific period of time, during the luteal phase of the menstrual cycle. Additionally, these mood symptoms do not occur in the absence of a menstrual cycle, as during reproductive events such as pregnancy or menopause.

Diagnosis It is important for clinicians to distinguish between PMDD and other medical and psychiatric conditions. Medical illnesses such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and migraine disorder can have features that overlap with PMDD. Additionally, psychiatric disorders such as depression or anxiety disorders can worsen during the premenstrual period and thus mimic PMDD. An estimated 40% of women who seek treatment for PMDD actually have a premenstrual exacerbation of an underlying mood disorder rather than PMDD. The best way to confirm the diagnosis of PMDD is by prospective daily charting of symptoms. Women with PMDD should experience a symptom-free interval between menses and ovulation. Although there is no consensus about the best instrument by which to confirm the diagnosis of PMDD, two well-validated scales for the recording of premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE) and the Prospective Record of the Severity of Menstruation (PRISM).

What Causes PMS and PMDD? Although the etiology of PMS and PMDD remains uncertain at present, researchers now concur that these disorders represent biological phenomena rather than purely psychological events. Recent research indicates that women who are vulnerable to premenstrual mood changes do not have abnormal levels of hormones or some type of hormonal dysregulation, but rather a particular sensitivity to normal cyclical hormonal changes. Fluctuations in circulating estrogen and progesterone cause marked effects on central neurotransmission, specifically serotonergic, noradrenergic and dopaminergic pathways. In particular, accumulating evidence implicates the serotonergic system in the pathogenesis of PMS and PMDD. Recent data suggest that women with premenstrual mood disorders have abnormal serotonin neurotransmission, which is thought to be associated with symptoms such as irritability, depressed mood and carbohydrate craving. There may also be some role for gamma amino-butyric acid (GABA), the main inhibitory neurotransmitter, in the pathogenesis of PMS/PMDD, however this remains to be defined. Likewise, the potential involvement of the opioid and adrenergic systems in these disorders has yet to be elucidated.

Non-Pharmacologic Treatment for PMS and PMDD Lifestyle changes can help to ameliorate the symptoms of PMS and PMDD. For women with mild symptoms, these interventions should be tried before pharmacological treatment. Although solid evidence is lacking, clinicians generally recommend that patients with PMS or PMDD decrease or eliminate the intake of caffeine, sugar, and sodium. Other helpful lifestyle modifications include decreasing alcohol and nicotine use and ensuring adequate sleep. Also, regular aerobic exercise has been demonstrated to have beneficial effects on both the emotional and physical symptoms of PMS/PMDD.

Certain nutritional supplements have also been shown to improve premenstrual symptomatology. A large, multicenter trial of calcium supplementation found that 1200 mg calcium a day significantly reduced both the physical and emotional symptoms of PMS. Other studies have demonstrated that Vitamin B6 in doses of 50-100 mg a day can have beneficial effects in women with PMS; however, patients must be cautioned that doses above 100 mg a day can cause peripheral neuropathy. Limited evidence suggests that magnesium (200-360 mg a day) and Vitamin E (400 IU a day) can provide modest relief of symptoms.

Herbal remedies may have some role in the treatment of premenstrual symptoms. One recent double-blind, placebo-controlled trial concluded that agnus castus fruit extract (1 tab a day), also known as chasteberry, significantly decreased premenstrual symptoms of irritability, anger, headache and breast fullness when compared to placebo. In another study, gingko biloba was found to improve PMS symptoms, particularly breast tenderness and fluid retention. Though early evidence suggested that evening primrose oil was a useful treatment of PMS, a recent review of studies found that it was no more effective than placebo. Other botanical remedies used clinically but which require further investigation include black cohash, St. John's Wort and Kava Kava.

Psychotherapy offers another non-pharmacologic approach to the treatment of PMS and PMDD. A recent study found that cognitive-behavioral therapy was as effective as fluoxetine (20 mg daily), in the treatment of women with PMDD. Other limited studies suggest that cognitive approaches can be useful in helping to reduce premenstrual symptoms.

Pharmacologic Treatment for PMS and PMDD

Psychotropic Medications Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological agents for the treatment of premenstrual mood symptoms. A significant body of evidence, including multiple double-blind, randomized studies, supports the effectiveness of SSRIs in reducing both the emotional, as well as physical symptoms, of PMS and PMDD. In general, women respond to low doses of SSRIs, and this treatment response usually occurs rapidly, often within several days. SSRIs may be prescribed continuously throughout the menstrual cycle or may be given in intermittent fashion during the luteal phase of the cycle. Also, other non-SSRI antidepressants which inhibit serotonin reuptake, including clomipramine (a tricyclic antidepressant), nefazadone (Serzone), and venlafaxine (Effexor) have evidence to endorse their use in the treatment of premenstrual symptoms.

Among other psychotropic medications used in the treatment of PMS and PMDD, benzodiazepine alprazolam (Xanax) has been shown to have benefit in reducing premenstrual symptomatology, in particular premenstrual anxiety. However, this medication should be prescribed cautiously, given its potential for addiction.

Hormonal Interventions Hormonal treatments of PMS and PMDD are based on the principle that suppression of ovulation eliminates premenstrual symptomatology. Results from studies using oral contraceptives (OCPs) to treat PMS and PMDD have been mixed. However, one recent study supported the usefulness of an oral contraceptive (Yasmin) containing drospirenone, an analog of the diuretic spironolactone, in the management of premenstrual symptoms.

Gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide, which suppress ovarian function, have been found to reduce premenstrual symptoms in most studies. These medications, however, cause estrogen to fall to menopausal levels and are thus associated with side effects such as hot flashes and vaginal dryness, as well as increased risk of osteoporosis. These side effects may be mitigated by "add-back" therapy with estrogen and progesterone. Similarly, danazol, a synthetic androgen, is an effective therapy for PMS/PMDD when given in doses high enough to inhibit ovulation. However, this medication is associated with significant androgenic side effects, including acne, hirsutism and weight gain.

Treatment Approach After the diagnosis of PMS or PMDD has been made through exclusion of other medical and psychiatric conditions, as well as by prospective daily ratings of symptoms, treatment can be initiated. For all women, simple lifestyle changes in diet, exercise and stress management are encouraged. These modifications have no associated risks and may provide significant benefit. Additionally, all women should be advised to continue daily charting of their premenstrual symptoms after diagnosis, as this can help both to determine treatment effectiveness and to give women a sense of control over their symptoms. For patients with mild physical and emotional symptoms of PMS, a trial of nutritional supplements, including calcium, magnesium, and vitamin B6 may also be considered.

In determining whether or not to start medication therapy, patient preference, the severity of the patient's symptoms, as well as the associated medication side effects must all be considered. For patients with severe symptoms of PMS, or with a diagnosis of PMDD, SSRIs are the first-line treatment. These medications can be dosed on a continuous or intermittent schedule depending on the patient's preference and the severity of her symptoms. If a woman does not show improvement in symptoms after 3 menstrual cycles, a trial with a different SSRI should be initiated. Additionally, if a patient has severely troubling side effects with one SSRI, she should be switched to a different medication.

For severe symptoms that fail to respond to any of the above strategies, medications that suppress ovulation, such as GnRH, may be considered. Because these medications induce a chemical menopause associated with troubling side effects and possible long-term consequence, they are not first-line agents for treatment of PMS or PMDD and should be used cautiously.