Brenda Penninx, Ph.D., and colleagues from The Johns Hopkins University, the University of Colorado in Denver and Vrije University in the Netherlands have found a positive correlation between vitamin B12 (cobalamin) deficiency and depression in physically disabled elderly women. Data from the Women’s Health and Aging Study were used to assess the link between vitamin B12 levels, folate levels and depression in 700 community-dwelling, physically disabled women ages 65 and over with no severe cognitive impairment.

Both vitamin B12 and folate are essential for several metabolic pathways in the central nervous system, and abnormal vitamin B12 and folate levels have been found in psychiatric patients. The researchers wanted to see if the same correlation was found within the general community as well.

All 700 women scored 18 or higher on the Mini-Mental State Examination and reported difficulty in performing tasks in at least two of four areas: mobility, upper-extremity abilities, higher-function tasks of independence and basic self-care. An in-home comprehensive exam was done of all subjects, and a blood sample was taken to determine possible vitamin B12 deficiency.

Since low serum levels are not specific in diagnosing tissue deficiency, high levels of two metabolites of vitamin-dependent conversions-in combination with low serum vitamin B12 and folate levels-were used to determine tissue vitamin deficiency. Vitamin B12 deficiency was determined by either a high or low cutoff, in order to evaluate any dose-response relationships. The high cutoff was a serum B12 level of less than 258 pmol/liter; a low cutoff was a serum B12 level of less than 148 pmol/liter. Folate deficiency was determined as a serum folate level less than 11.4 nmol/liter and a homocysteine level higher than 13.9 pmol/liter.

Depressive symptoms were scored according to the Geriatric Depression Scale. A score lower than 9 indicated no depression, subjects with mild depression scored from 10 to 13, and those with severe depression scored 14 or higher.

Of the 700 participants, 478 (68.3%) were not depressed, 100 (14.3) had mild depression, and 122 (17.4%) had severe depression. Prevalence of vitamin B12 deficiency was 17.3% (n=121) at the higher cutoff and 4.6% (n=32) at the lower cutoff. Folate deficiency was found in 7.1% (n=50) of all subjects.

Vitamin B12 deficiency (scored at either high or low cutoff) was present significantly more often among depressed subjects than among controls. No associations with vitamin B12 deficiency were found for mild depression, but the risk of severe depression was twice as high in women with vitamin B12 deficiency as in controls (odds ratios of 2.05 and 2.09 for high and low cutoffs, respectively). Folate deficiency was not associated with depression status.

The researchers summarized by stating, “Clinicians and other health care providers need to be aware of the high prevalence of vitamin B12 deficiency in disabled older women, and they need to screen and treat appropriately”.

THE PHARMACIST’S ROLE IN PMDD

Premenstrual dysphoric disorder is a fairly recent discovery in women’s health; yet, it currently costs the nation millions of dollars a year in direct and indirect costs.Most costs associated with PMDD patients are related to days missed from work or reduced work performance due to symptoms. Premenstrual dysphoric disorder symptoms result in a huge economic and health burden for our nation. To reduce the incidence of PMDD, it is crucial to understand the criteria and many different treatment options available.

When counseling a patient who may be suffering from PMDD, it is important to seek information. Table 6 provides a list of useful questions for the pharmacist to ask. The patient’s complete medical and personal history should be carefully reviewed and assessed. It is important for the pharmacist to then make a decision to triage the patient to a physician or begin to work with the patient to institute an effective self-care program.

If the self-care path is selected, nonpharmacological treatment should be considered first before medication. Pharmacists play a key role in counseling patients on the nonpharmacological and pharmacological treatments available. Understanding the patient helps the pharmacist to individualize patient therapy. A pharmacist should be well educated on the symptoms, treatment approaches, and strategies. Therefore, the patient should be encouraged to chart and identify target symptoms for at least two consecutive menstrual cycles. A healthy, well-balanced diet including sufficient vitamins, calcium, and minerals should be recommended. The patient should be informed of the negative association between increased caffeine, alcohol, nicotine, and drugs of abuse as triggers for specific premenstrual dysphoric disorder symptoms. Supportive therapy should also be discussed. In addition to nonpharmacological therapies, pharmacists should always discuss indications, side effects, and common concerns regarding medications to reduce symptoms of PMDD. The pharmacist should remember that premenstrual dysphoric disorder is an emotionally, socially, mentally, and physically debilitating condition. Respecting the concerns and confidentiality of the patient is significant for optimizing patient care. Patients need to aware of the wide spectrum of symptoms experienced in PMDD. Furthermore, because premenstrual dysphoric disorder affects the patient both emotionally and physically, it often interferes with family and relationships. The pharmacist should be sympathetic to all individuals involved in the care of the PMDD patient.

SUMMARY AND CONCLUSION

The most important point to remember when selecting the appropriate course of treatment for premenstrual dysphoric disorder is that therapy must be tailored to the individual patient’s needs and responses. Studies recommend nonpharmacological adjustments prior to initiating drug therapy. First-line pharmacological therapy includes SSRIs; second-line agents are anxiolytic agents. Finally, ovulation suppressors, oral contraceptives, or oophorectomy could all be considered after nonpharmacological and pharmacological agents (i.e., first- and second-line agents) fail. However, before changing classes of drugs or considering alternatives such as ovulation suppressors, it is important to note that the timeline to alleviation of symptoms may differ among patients. While many patients may notice relief of symptoms within three to five days of starting therapy during the luteal phase, many other patients may need to continue therapy for several cycles before noticing improvement. Although no data are currently available as to how long therapy should be continued, at least nine to 12 months of treatment is recommended. Once again, the pharmacist plays a crucial role in the care of the PMDD patient with regard to symptoms and treatment options.

As the pathophysiology of PMS and PMDD suggests, symptoms are associated with the elevation and decline of sex hormones during ovulation. As symptoms are not found before menarche or after menopause, studies have focused on ovulation suppression to relieve these symptoms. If ovulation were suppressed, the rise and fall of these hormones would then be inhibited, resulting in a reduction or complete cessation of symptoms. Medical oophorectomy is the term used to describe using medications in the suppression of ovulation. GnRH agonists have been indicated to treat premenstrual dysphoric disorder and result in a hypoestrogenic state. Some GnRH agonists studied are leuprolide and buserelin, both found to be superior to placebo in reducing emotional and physical symptoms related to the menstrual cycle.

The disadvantages of using GnRH agonists include cost and negative side-effect profiles, being associated with menopausal symptoms, e.g., hot flashes, vaginal dryness, depression, headaches, and muscle aches. Also, long-term effects of these drugs may include osteoporosis or heart disease. GnRH agonists have yet to be further researched to understand the risks and benefits associated with this class of drugs. In addition to GnRH agonists, the synthetic androgen, danazol, has been studied in the treatment of PMDD. Doses of 200 mg a day of danazol were found to reduce many symptoms related to ovulation such as mastalgia (muscle pain) and migraines. Adverse effects to be aware of when prescribing danazol include estrogen deficiency side effects (e.g., menstrual irregularities and hot flashes), androgenic side effects (hirsutism, acne, and deepening voice), and lipid changes (decreased high-density lipoprotein cholesterol and increased low-density lipoprotein cholesterol).

As ovulation suppression has been shown to decrease symptoms associated with premenstrual dysphoric disorder, it is logical to consider the use of oral contraceptives. However, few studies have been conducted with conclusive evidence that specific contraceptives are advantageous in PMDD treatment. The most common concern is that the symptoms linked to birth control medications are often observed with those of the menstrual cycle (e.g., breast tenderness, headache, bloating, and depression). The challenge is to find the “right” birth control medication that provides relief from menstrual symptoms with minimal side effects. The new formulations of oral contraceptives attempt to achieve the right balance of estrogen and progestin to help decrease side effects. However, using oral contraceptives for premenstrual dysphoric disorder symptoms remains controversial, and no single oral contraceptive has been indicated as beneficial when side effects are considered.

Although emotional and psychological symptoms are often the focus of treatment in PMDD patients, it is important to remember that physical symptoms of premenstrual dysphoric disorder are similar to PMS. As a result, clinicians and health care providers have to be familiar with treatment options available for particular symptoms. The “symptom-based approach” is often the most successful when treating PMDD patients. Physical symptoms to be aware of include dysmenorrhea or cramps, headaches, weight gain and bloating, and mastodynia (breast tenderness).

Dysmenorrhea and Cramps and Headaches: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often recommended to reduce menstrual pain. These include ibuprofen, ketoprofen, naproxen, or cyclooxygenase-2 inhibitors, such as celecoxib.

Weight Gain and Bloating: Sufficient clinical data supports the use of spironolactone, an aldosterone antagonist with potassium-sparing properties, to treat weight gain or bloating. The recommended dose of spironolactone is 25 mg two to four times a day during the luteal phase. Triamterene and hydrochlorothiazide have also been used, but little clinical data exist on their therapeutic effectiveness for these symptoms.

Mastodynia: Although NSAIDs are often used for the relief of breast tenderness related to premenstrual dysphoric disorder, vitamin E or primrose oil has also been used as a nutritional modality for this condition. Bromocriptine, at 1.25 to 7.5 mg per day, during the luteal phase has been clinically studied and supported.Danazol has also been studied for its antiestrogenic properties in the treatment of mastodynia, and studies have found positive results in its use. Additionally, using tamoxifen citrate in the luteal phase has also been studied, but conclusions regarding its use in PMDD are controversial.

Surgical Intervention and Management

Pharmacological and nonpharmacological treatments sometimes fail. In these instances, the option of bilateral oophorectomy (”removal of ovaries”) should be considered. However, this should only be a last resort because of its irreversible nature and because patients may experience menopausal symptoms or develop osteoporosis. The patient’s demographic information and medical history should be assessed carefully before considering surgery.

Pharmacological Therapy for Emotional and Psychological Symptoms

Often, nonpharmacological interventions are insufficient for adequate menstrual relief for patients suffering from premenstrual dysphoric disorder. Dietary modifications that may then be recommended include daily calcium, magnesium, and L-tryptophan supplementation. These modifications have been clinically studied in premenstrual syndrome patients and are therefore assumed to be beneficial to the PMDD patient. Recommendations supported by controlled studies include 1,200 mg of calcium carbonate per day in divided doses, 50 to 100 mg of magnesium twice a day (up to 60 mg/day), 400 U of vitamin E per day, or 50 to 100 mg of vitamin B₆ per day. Supplementation of L-tryptophan to reduce symptoms of PMDD has been indicated with limited data. The daily recommended amount of L-tryptophan is 6 g from the time of ovulation until day 3 of menses.

In addition to nutritional supplements, herbal products have also been studied to treat premenstrual dysphoric disorder. Dong quai is a coumarin derivative widely used in China for menstrual cramps and irregular menses. Black cohosh is often recommended to patients who suffer from dysmenorrhea and hot flashes associated with menopause. Similarly, blue cohosh can be used for menstrual cramps and stimulation of menstrual flow. Valerian is indicated for patients with insomnia related to PMDD. Although these herbal products may relieve some symptoms of premenstrual dysphoric disorder, they cannot be recommended because little is known regarding their dosing, efficacy, and safety. If a patient insists on the use of herbal products, it is essential to evaluate her current drug therapy (both prescription and nonprescription) to prevent significant drug­herb interactions. Some herbal products most commonly used by patients for PMDD include evening primrose oil (contains prostaglandin to reduce breast pain), kava kava (anxiety, stress, restlessness, and premenstrual cramps), melatonin (sleep-wake cycle disorder or insomnia), passion flower (anxiety and restlessness), St. John’s wort (depression), and valerian (insomnia and restlessness). With patients using herbals, it is important to discuss the specific drug­herb interactions that may decrease or increase drug levels in the body, resulting in toxicity or subtherapeutic levels of drug.

Pharmacological therapies in patients with premenstrual dysphoric disorder in whom lifestyle modifications fail include prescribed SSRIs, antidepressants, anxiolytics, and ovulation suppressors. According to ACOG, an SSRI is considered a first-line agent in treating PMDD.Its effectiveness is strongly supported by the association between reduced serotonin neurotransmission and PMDD symptoms such as depression, sleep impulse, anxiety, and carbohydrate cravings.As can be expected, many hypotheses suggest that serotonergic dysregulation may be partly responsible for symptoms of premenstrual dysphoric disorder. Most studies performed during the last 10 years have shown SSRIs to be efficacious for its treatment. Fluoxetine was the first SSRI that was approved by the FDA for this disorder. Placebo-controlled studies have concluded that serotonergic antidepressants, particularly fluoxetine and sertraline, are more effective than placebo. Both have been shown to improve emotional and physical symptoms associated with PMDD and also to enhance psychosocial functioning, work performance, and quality of life. Results of randomized clinical trials of fluoxetine and sertraline conclude that their effectiveness in PMDD treatment is clinically significant.Fluoxetine, at doses of 20 to 60 mg per day, and sertraline, at doses of 50 to 150 mg per day, have been studied and recommended for premenstrual dysphoric disorder. Results of the fluoxetine studies concluded that when larger doses were used in some patients, no clinically significant advantage in efficacy was observed. Instead, patients given 60 mg of fluoxetine per day experienced more side effects than those given the smaller doses. However, no similar clinical findings were reported in those studies using higher doses of sertraline.

Although fluoxetine and sertraline are the two antidepressants most widely studied for PMDD, other antidepressants have also been used. For example, venlafaxine is a newer antidepressant that works slightly differently than SSRIs by inhibiting both serotonin and norepinephrine reuptake. Treatment with 50 to 200 mg per day of venlafaxine in a small number of female patients has been shown to be more effective than placebo.Finally, paroxetine and citalopram have also been studied as antidepressants to treat premenstrual dysphoric disorder.

Using anxiolytic agents, particularly alprazolam, for PMDD has been controversial. Some studies have shown it to be more beneficial than placebo, whereas others have indicated alprazolam to be as effective as placebo. However, these studies focused more on the premenstrual symptoms associated with premenstrual syndrome. Thus far, no large study has been performed to examine anxiolytic agents as premenstrual dysphoric disorder treatment. Because alprazolam is a triazolobenzodiazepine anxiolytic, the obvious caution is the risk of dependence and tolerance. Buspirone is another anxiolytic considered as treatment. Few studies have shown that buspirone, at a dose of 20 mg per day, is more effective than placebo. Significantly, although anxiolytic agents are being studied for PMDD, serotonin agents remain the drugs of choice and should be first-line therapy before initiating anxiolytic therapy. To date, fluoxetine and sertraline are the only FDA-approved SSRIs for the treatment of premenstrual dysphoric disorder. Anxiolytic agents should only be considered if a patient does not tolerate the SSRIs or as adjunctive therapy.

Pharmacologically, when treating patients, it is crucial to understand the menstrual cycle and rise and fall of sex steroids. Many drugs have only been studied in the administration of certain phases of the menstrual cycle. Research has shown that taking these drugs “intermittently” or “semi-intermittently” has been more effective than continuous administration. Intermittent doses require administration only during the luteal phase, whereas semi-intermittent require lower doses during the follicular phase and higher doses during the luteal phase. Fluoxetine and sertraline are recommended during the luteal phase. Alprazolam has been found to be beneficial in both the luteal and follicular phases. Buspirone has also been shown as more effective during the luteal phase. Overall, a luteal phase administration of these agents mentioned previously has been found to not only reduce the side-effect profile but also to reduce the cost of treatment.

Some physicians prefer to use medications at higher doses during the luteal phase and then employ lower doses during the follicular phase. It is important to understand the patient’s cycle and review the menstrual calendar and symptoms experienced at particular phases to provide optimal relief. Patients should be very specific and thorough when recording symptoms associated with their menstrual cycle, as it is extremely helpful to pharmacists and physicians in tailoring their medication regimen. Tables 4 and 5 summarize the drugs currently available that are studied for premenstrual dysphoric disorder treatment.

Once a patient meets the DSM-IV criteria and is diagnosed with premenstrual dysphoric disorder, therapy should be initiated. Consistent with many disorders and disease states, nonpharmacological therapy should be attempted initially.

Nonpharmacological Therapy

Nonpharmacological therapy consists of dietary modifications, moderate regular exercise, stress management, and supportive therapy. Dietary modifications include reduction in daily salt, caffeine, and alcohol intake. Although these modifications are not confirmed with substantial evidence, many patients have been found to benefit with these changes. Some studies also suggest smaller, more frequent meals with high carbohydrate content or complex carbohydrate drinks. Reducing chocolate consumption has been recommended, but no clinical link to alleviation of symptoms has been found.

Moderate regular exercise has been shown to modify endorphin levels and improve mood during premenstrual dysphoric disorder. Clinical studies have not found any major correlation between exercise and improved mood, but epidemiological studies have validated a positive relationship, i.e., mood improves with increasing exercise.

Supportive therapy includes family support through discussions and daily symptom recordings to determine menstrual links between symptoms and behavior. Again, the use of supportive therapy has not been well studied, but anecdotal information implies that it is beneficial for some patients. It allows women to learn more about the timing of their symptoms as well as the triggers and exacerbations. Monitoring or recording symptoms may then enhance awareness and help patients make lifestyle changes to prevent exacerbations and foster a decline in symptoms.Another nonpharmacological option found to be effective in improving symptoms is cognitive behavioral relaxation therapy. This includes yoga, relaxation exercises, stress management exercises, cognitive therapy, and group coping skills.

CRITERIA FOR DIAGNOSIS

An estimated 3% to 8% of women of reproductive age suffer from premenstrual dysphoric disorder. Health care providers have made many attempts to define PMDD and its characteristics to help distinguish it from the common and simple symptoms of PMS.

The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) defines PMDD as a “depressive disorder not otherwise specified,” emphasizing its emotional and cognitive-behavioral symptoms. To be diagnosed with premenstrual dysphoric disorder, a patient must experience at least five of 11 symptoms given in DSM-IV. Table 2 lists the criteria. According to DSM-IV, the five symptoms must occur during the luteal phase to eliminate diagnosis of PMS.

If the timing of symptoms is not considered, patients may be misdiagnosed, or their condition can be confused with psychiatric disorders (e.g., major depression and generalized anxiety). Patients may also have other menstrual disorders such as endometriosis and dysmenorrhea that may be misinterpreted as premenstrual dysphoric disorder if the guidelines are not followed. Regarding complaints of PMDD, it is important to note the cyclic pattern of symptoms that occur during the menstrual cycle. Patients with PMDD most often experience symptoms a week before menstruation, which abate with menses. The timeframe of symptoms is crucial to prevent confusion with other preexisting or comorbid disease states.

In addition to having the required five symptoms during the luteal phase, symptoms must be confirmed for two consecutive menstrual cycles.Unfortunately, there are no clinical laboratory tests or scientific methods to determine a patient’s symptoms aside from subjective data. Laboratory tests (e.g., thyroid function tests, complete blood count, and FSH and estradiol levels) are often only used to rule out other disease states or causes of symptoms. Therefore, symptoms must be carefully recorded to understand menstrual-related conditions. Patients are strongly encouraged to maintain a diary of symptoms before and after menses to determine the time at which these symptoms occurred. It is essential to understand whether the symptoms and symptom-free phases correlate with the patient’s luteal and follicular phases. Once again, this is important to prevent misdiagnosing a patient with PMDD. A written log is also important in establishing baseline symptoms to determine whether they are improving or worsening with treatment and the patient’s age. (See Table 3 for laboratory tests, procedures, and assessments.) Also, a few standardized tests and questionnaires have been developed to measure a patient’s functional impairment, mood dimensions, and quality of life. Some common standardized tests and questionnaires available to rate a patient’s symptoms include PMS Diary, Menstrual Distress Questionnaire, Hamilton Depression Rating Scale, and Quality of Life Questionnaire. Each questionnaire is designed to evaluate a patient’s symptoms throughout the menstrual cycle. When counseling patients on the questionnaires, it is critical to inform them of the importance of recording baseline symptoms. The goal of therapy is to reduce premenstrual symptoms by at least 50% or more. If a patient finds that her premenstrual symptoms are similar to postmenstrual symptoms, the minimum goal of therapy is reached. It is recommended that at least three menstrual cycle symptoms be recorded to determine the effectiveness of treatment and to allow for proper dose and therapy changes.

PMS/PMDD SYMPTOMS

Premenstrual syndrome affects as many as 75% of women of reproductive age at some point in their life. However, studies have not defined an exact age-group or time course for this syndrome to occur. But one study suggests that the 25 to 34 age-group of women was the most commonly affected (10.4%) compared to the 18 to 24 age-group (8.7%) and the 35 to 44 age-group (4.5%), which were not affected as often.

Some of the most common emotional, physical, and behavioral symptoms attributed to both premenstrual syndrome and premenstrual dysphoric disorder are listed in Table 1. As shown, many symptoms experienced during the menstrual cycle are common to both PMS and PMDD. Hence, without further evaluation, premenstrual dysphoric disorder can easily be misdiagnosed as PMS. Women with mild or moderate symptoms of PMS often complain of the physical symptoms, which often include engorgement of the breasts, body aches, and bloating/weight gain. However, some women also experience the behavioral and emotional symptoms associated with premenstrual dysphoric disorder. Some patients with premenstrual dysphoric disorder suffer from physical, behavioral, and emotional symptoms similar to those of premenstrual syndrome. Yet, unlike premenstrual syndrome, premenstrual dysphoric disorder symptoms are rarely relieved by simple analgesics and often need medical intervention. Also, symptoms of premenstrual dysphoric disorder are emotionally debilitating. Hence, extensive studies have been conducted to better understand PMDD and to differentiate the diagnosis of premenstrual dysphoric disorder from premenstrual syndrome.

ETIOLOGY AND PATHOPHYSIOLOGY

While many studies have focused on the predisposing factors related to premenstrual dysphoric disorder, the relative contributions to this disorder are unclear. Small studies of monozygotic twins have suggested a hereditary link to premenstrual symptoms. Other considerations include a patient’s onset of menses. Onset at a young age (i.e., less than 11 years old) has been found to be an increased risk factor for many gynecological disorders such as breast cancer, endometriosis, and of importance to this article, premenstrual symptoms. In addition to the genetic and developmental factors that may contribute to the risk of PMDD, research has shown that a history of major depressive disorder, bipolar disorder, postpartum depression, and family history of mood disorders of premenstrual depression may increase a woman’s risk for premenstrual dysphoric disorder. Studies have also indicated that women with PMDD are at a higher risk for lifetime history of depression compared to women without premenstrual dysphoric disorder (30% to 76% vs. only 15%, respectively).

The ACOG has indicated that PMDD symptoms should occur during the late luteal phase of the menstrual cycle, resolve within the onset of menses, and then be absent during menses. This pattern helps in the differential diagnosis. The occurrence of symptoms during the late luteal phase is also important to note when administering certain medications (as discussed later in this article).

Although the pathophysiology of premenstrual dysphoric disorder is not entirely understood, many hypotheses have been proposed to explain the mechanism by which symptoms of PMDD occur. The first and most common hypothesis is an abnormality that exists in the patient’s serotonergic neurotransmitters triggered by normal hormonal changes during the luteal phase of menses. Other hypotheses include deficiencies in hormonal production and nutritional deficiencies and excesses. The first hypothesis suggests a close link between PMDD symptoms and serotonin. The latter describes the use of nutritional and hormonal supplements for the relief of symptoms.

These hypotheses are associated with the pathophysiology of the menstrual cycle. The rise and fall of particular hormones and the biological changes that occur during the cycle provide a logical explanation for most of the symptoms women experience with premenstrual dysphoric disorder. The menstrual cycle involves the hypothalamic-pituitary axis (HPA). Key elements of this process include gonadotropin-releasing hormones (GnRHs), gonadotropins, ovarian hormones, neurotransmitters, and neuropeptides. The HPA is responsible for the secretion and regulation of hormones that control ovulation. The hypothalamus produces GnRH, which in turn regulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. The two main phases in the menstrual cycle are the follicular phase (days 1 to 14) and luteal phase (days 15 to 28). The follicular phase occurs when estrogen levels are low, which then stimulates the release of FSH and LH. The rising FSH and LH levels cause ovarian follicular growth that leads to a positive feedback, resulting in increased estrogen production. High estrogen levels cause an LH surge, finally leading to ovulation (around day 14). After ovulation, the mature follicle becomes the corpus luteum, which increases estrogen and progesterone levels. This marks the beginning of the luteal phase. The corpus luteum ultimately degenerates, at which time estrogen and progesterone levels decrease. The degeneration of the corpus luteum causes the uterine lining to break down. This breakdown marks the onset of menstruation. Figure 1 depicts and summarizes the menstrual cycle.

Figure 1. Summary of the Menstrual Cycle

Understanding the phases of the menstrual cycle is crucial, as many studies have strongly supported that ovarian hormones are linked to symptoms of premenstrual dysphoric disorder. Symptoms have been shown to decline with an inhibition of ovulation, surgical ovariectomy, or menopause. Thus, these conclusions lead to current treatment options such as ovulation suppressors. Research suggests that low estrogen levels in the brain during the luteal phase play a role in PMDD symptoms and also that declines in serotonin levels may lead to irritability, decreased energy, and mood changes. This evidence explains the use of selective serotonin reuptake inhibitors (SSRIs) to treat PMDD. Treatment based on the pathophysiology of premenstrual dysphoric disorder is discussed later in this article.

SM is a 24-year-old Asian Indian female who presents to her gynecologist with a chief complaint of “severe abdominal pain, breast tenderness, headaches, and weight gain” during her menstrual cycle. She states that her cramps feel like “pins through her stomach.” Her boyfriend states that SM cries sporadically during her menstruation and is often depressed. He also states that she appears to be a lot more anxious and tense during this time of the month. In addition, he has observed that her emotional and mental symptoms during her menstruation result in a strain in their relationship. SM experiences increased appetite and a marked lack of energy during this time. Although both SM and her boyfriend are aware of the premenstrual symptoms that most women experience during the menstrual cycle, they are convinced that her emotional disturbances during her menstruation need medical attention.

SM’s past medical history is insignificant, but her social history is of concern. She states that she drinks about three cans of Coke a day and doesn’t follow a “healthy” diet. Her usual diet consists of no breakfast, a small lunch consisting of “junk” food, and a vegetarian dinner. Furthermore, she denies following any exercise regimen. SM states that she takes about four to five 200-mg tablets of ibuprofen a day during her menstrual cycle with minimal relief.

The menstrual cycle: fluctuating levels of estrogen and progesterone contribute to symptoms of PMDD

Symptoms of menstruation have long been defined and studied, but clinicians have been struggling to define the more severe form of premenstrual syndrome (PMS) from which women suffer. This term has often been used to describe the emotional, behavioral, and physical symptoms women experience before menses, which subside following menstruation. Symptoms of PMS are experienced by more than 75% of women. More significantly, 3% to 8% of women suffer from the more severe form of PMS known as premenstrual dysphoric disorder (PMDD).

Over the last 20 years, PMDD has been studied extensively regarding its pathophysiology and treatment. Often, premenstrual dysphoric disorder is mistaken for PMS. Although PMDD is similar to PMS in that it causes much distress in women’s lives, it differs in its diagnostic criteria. Originally, in the early 1900s, the term late luteal phase dysphoric disorder (LLPDD) was used to describe the symptoms experienced by women during the late luteal phase of their menstrual cycle. As these symptoms were studied further, the term premenstrual syndrome was coined in the 1950s and used instead to describe the physical and psychological symptoms occurring a few weeks before menses.

It was not until about 1990 that a more severe form of premenstrual syndrome was established and termed premenstrual dysphoric disorder. In April 2000, the American College of Obstetricians and Gynecologists (ACOG) published criteria for the diagnosis and treatment for PMDD, contributing to the awareness of this disorder and the study of further management. Premenstrual dysphoric disorder is not understood as well as PMS, but the many similarities between them have provided clinicians with a better understanding of its possible treatment options and pathological existence.

Although PMDD affects a small percentage of women, studies have found it to be a debilitating disorder that results in disruptions in relationships, work, and/or social activities at levels similar to those encountered with major depression. For health care providers, it is essential to understand the numerous aspects of this disorder by focusing on definitions, diagnosis, and treatment options.

Drug lessens severity of premenstrual dysphoria.

Intermittent dosages of fluoxetine (Prozac/Lilly) given during the luteal phase of the menstrual cycle may help women suffering from PMDD (premenstrual dysphoric disorder), studies suggest. Premenstrual dysphoric disorder, a severe variant of premenstrual syndrome, affects 3%-5% of women during their reproductive years, causing depression, anxiety, tension, lability, and irritability. A review of 12 clinical trials led researchers to conclude that, at 20 mg/day, fluoxetine reduces mood symptoms, physical symptoms, and social impairment in women with premenstrual dysphoric disorder and is well-tolerated.