Managing the premenstrual syndrome

The definition, classification, proposed etiologies, diagnosis, and treatment of the premenstrual syndrome (PMS) are discussed, and guidelines for the clinical management of PMS are presented. PMS encompasses a cluster of physical and psychosocial symptoms that recur during each menstrual cycle. Proposed etiologies for the syndrome include a hormonal imbalance between estrogen and progesterone, pyridoxine hydrochloride deficiency, hypoglycemia, excess prostaglandin production, and increased aldosterone concentrations in the luteal phase of the menstrual cycle. Diagnosis of PMS is usually based on a patient's history of recurrent symptoms accompanied by a seven-day, symptom-free period in the first half of the menstrual cycle. Management of PMS is complicated by the difficulty in diagnosing the syndrome and its unclear etiology. If possible, conservative nonpharmacologic treatment should be tried initially; suggested measures include modifications in diet, exercise, substance use, stress factors, rest patterns, and social support. Pharmacologic treatment should be considered when conservative therapies are ineffective or when PMS symptoms are more severe. Although most therapies are empirical, treatment with progesterone, pyridoxine, bromocriptine, or diuretics might prove beneficial. Once the decision is made to initiate drug therapy, the treatment regimen should be individualized and based on the patient's PMS symptom complex. The clinical management of PMS is complicated by the lack of well-designed clinical investigations of proposed treatments. Future research should be directed toward evaluating the efficacy of proposed therapeutic regimens.     

Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.     

The premenstrual syndrome: a review of the present status of therapy

Treatment of the premenstrual syndrome is complicated by many factors, but principally by its unknown aetiology. In addition, diagnosis, definition and symptom evaluation methods are unclear. The multitudinous studies of treatment regimens have been largely inconclusive; this is partly due to difficulties in numerically evaluating the symptoms, but more to the lack of appreciation of the marked placebo effect which has been estimated as being up to 50%. The majority of studies have been open studies, and therefore interpretation of the results have been almost impossible. The end result is that great claims have been made for a large number of therapeutic agents on ill-founded evidence. Some of the drugs used in the treatment of the premenstrual syndrome, however, have been better evaluated than others, although even with those studied more extensively results have often been variable. Thus, hormonal agents such as progestagens and oral contraceptives, diuretics, pyridoxine, bromocriptine and danazol have been effective in some studies but not universally so. The latter 2 agents seem to be effective in relieving breast symptoms, but have only a limited effect on other symptoms. It is therefore important to realise that one drug does not cure all patients or all symptoms, although it is often claimed that this is the case. It has been suggested that more than 40% of women suffer from premenstrual syndrome. Greater awareness of the problem, both by patients and doctors, necessitates a more rational approach to therapy.     

Lack of beneficial effects of clonidine in the treatment of premenstrual dysphoric disorder: results of a double-blind, randomized study

OBJECTIVES: To test the effects of clonidine in comparison with active placebo on premenstrual symptoms, mood scores and norepinephrine (NE) concentration, in women with premenstrual dysphoric disorder (PMDD). METHODS: Twelve women with prospectively confirmed PMDD were randomly assigned to oral 0.3 mg/day clonidine, as an active treatment, or 10 mg/day loratadine, as an active placebo, for 2 months each using a double-blind, cross-over design. NE concentration, premenstrual symptom ratings and mood scales were measured on three occasions: at pretreatment, after clonidine treatment and after placebo treatment. All patients were free of current psychiatric co-morbidity and medication use. RESULTS: There were no significant differences between clonidine and placebo for mood scales or premenstrual symptom ratings, though clonidine significantly suppressed NE concentration and produced more side effects in comparison with placebo. CONCLUSION: Compared with an active placebo clonidine demonstrated no beneficial changes in mood and premenstrual symptoms in women with PMDD.     

Evaluation and management of premenstrual syndrome and premenstrual dysphoric disorder

OBJECTIVE: To review premenstrual disorders, their varied symptoms, possible etiology, and treatment options. DATA SOURCES: Published articles identified through MEDLINE (1966-2001) using the search terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) and the additional terms treatment and etiology. Additional references were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: PMS refers to a group of menstrually related disorders that are estimated to affect up to 40% of women of childbearing age. The varied symptoms of PMS include mood swings, tension, anger, irritability, headache, bloating, and increased appetite with food cravings. PMS symptoms occur during the luteal phase of the menstrual cycle and remit with the onset of menstruation or shortly afterward. Approximately 5% of women with PMS suffer from PMDD, a more disabling and severe form of PMS in which mood symptoms predominate. Because no tests can confirm PMS or PMDD, the diagnosis should be made on the basis of a patient-completed daily symptom calendar and the exclusion of other medical disorders. The causes of PMS and PMDD are uncertain, but are likely associated with aberrant responses to normal hormonal fluctuations during the menstrual cycle. For most women, symptoms can be relieved or reduced through lifestyle interventions, such as dietary changes and exercise, and drug therapy with hormonal or psychotropic agents. For PMDD, selective serotonin reuptake inhibitors have recently emerged as first-line therapy. Certain dietary supplements, including calcium, also may be an option for some women. CONCLUSION: PMS and PMDD are complex but highly treatable disorders. Pharmacists can improve the recognition and management of these common conditions by providing patient education on premenstrual symptoms and counseling women on lifestyle interventions and pharmacotherapy to relieve their discomfort.     

Premenstrual exacerbations of mood disorders

Premenstrual exacerbation of mood disorders has received little attention, despite the recent interest in premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). Differentiating between PMDD/PMS and other disorders, which worsen premenstrually, is a poorly understood diagnostic challenge. Controversy also focuses on a possible coexistence of PMDD and other mood disorders. This review discusses the differences between mood-disorder exacerbations and premenstrual disorders, evidence for premenstrual magnification of mood disorders, and possible mechanisms for these variations as well as clinical implications.     

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests

Rationale Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. Objective The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Subjects and methods Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 a.m. Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. Results As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. Conclusion The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.     

Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder

The objective of this study was to examine the efficacy and tolerability of intermittent dosing of venlafaxine for the treatment of premenstrual dysphoric disorder. One hundred and twenty-four women aged 18 to 45 years, with regular menstrual cycles and who reported significant premenstrual symptoms, were assessed prospectively to confirm their diagnosis of premenstrual dysphoric disorder. Twenty subjects with confirmed premenstrual dysphoric disorder entered a single-blind, placebo phase (1 cycle). Placebo nonresponders (n = 12) received 2 cycles of intermittent (premenstrual) treatment with venlafaxine (75 to 112.5 mg/d). Subjects initiated treatment 14 days before the anticipated onset of menses and discontinued it on the second day of bleeding. Doses could be adjusted after cycle 1 based on subjects' response and tolerability. Response to treatment was assessed based on changes in the Daily Rating Severity of Problems and Premenstrual Tension Syndrome Questionnaire scores from baseline (before the placebo cycle), as well as Clinical Global Impression-Severity scores. Discontinuation symptoms were assessed between treatment cycles, using the Discontinuation-Emergent Signs and Symptoms questionnaire. Eleven subjects concluded 2 cycles of intermittent dosing with venlafaxine. Nine subjects (81.8%) showed satisfactory response based on Clinical Global Impression of < or = 2. Changes in Daily Rating Severity of Problems scores and subscores (depression, physical symptoms, and anger) and in Premenstrual Tension Syndrome Questionnaire scores were significant (P < 0.05 for all comparisons, Wilcoxon tests). Intermittent treatment was well tolerated. This preliminary report suggests that premenstrual use of venlafaxine is an efficacious and well-tolerated treatment for premenstrual dysphoric disorder.     

Diagnosis and treatment of premenstrual dysphoric disorder: an update

Premenstrual dysphoric disorder (PMDD) appears in the appendix of the DSM-IV under the heading 'depressive disorder not otherwise specified'. Yet, recently, a group of experts reached a consensus that PMDD is a distinct clinical entity with characteristic symptoms of irritability, anger, internal tension, dysphoria, and mood lability. PMDD is the more severe form of premenstrual symptomatology, whereas premenstrual syndrome (PMS) is milder and more prevalent and both must be differentiated from premenstrual magnification/exacerbation of an underlying major psychiatric disorder or a medical condition. Accurate assessment and diagnosis of significant premenstrual symptomatology is paramount and can be influenced by subjective perception, retrospective versus prospective reporting, and cultural context. The serotonergic system, which is in a close reciprocal relationship with the gonadal hormones, has been identified as the most plausible target for intervention. Results from randomized placebo-controlled trials in women with PMDD have clearly demonstrated that serotonin reuptake inhibitors (SSRIs), with daily or intermittent dosing, have excellent efficacy and minimal adverse effects and should be considered first-line treatment. Luteal phase only SSRI administration may offer an attractive treatment option for a disorder that is itself intermittent. Hormonal interventions, in particular the suppression of ovulation will eliminate premenstrual symptomatology; however, the benefits-risk ratio of these approaches should be carefully evaluated with the patient.     

Fluoxetine in the treatment of premenstrual syndrome

Despite many associations between premenstrual syndrome (PMS) and major depression, there have been no placebo-controlled trials of an antidepressant in this disorder. We conducted a double-blind, randomized, placebo-controlled trial of fluoxetine in the treatment of severe PMS. The diagnosis of PMS was made using daily, prospective, self-rating forms over two menstrual cycles. Women who continued to meet criteria for PMS after a single-blind trial of placebo during one menstrual cycle were randomly assigned to treatment for two menstrual cycles with either fluoxetine at 20 mg/day (n = 9) or placebo (n = 6). Eight of the 9 subjects receiving fluoxetine responded to treatment, whereas only 1 of the 6 receiving placebo responded (p less than .025). All subjects on fluoxetine elected to continue with this treatment after completion of the study. These preliminary results suggest that fluoxetine is an effective and well-tolerated treatment for severe PMS.     

Review of fluoxetine and its clinical applications in premenstrual dysphoric disorder

The largest number of antidepressant treatment trials in premenstrual syndrome and premenstrual dysphoric disorder (PMDD) have been conducted with fluoxetine. Fluoxetine and other selective serotonin re-uptake inhibitors (SSRIs) clearly reduce premenstrual emotional and physical symptoms and improve premenstrual psychosocial functioning. Fluoxetine was the first SSRI to be approved by the FDA as a treatment for the emotional and physical symptoms of PMDD. Fluoxetine 20 mg has been reported to be effective for emotional and physical premenstrual symptoms with continuous daily dosing (every day of the menstrual cycle) and with luteal phase daily dosing (from ovulation to menses). In addition, premenstrual emotional symptoms have been reported to improve with fluoxetine 10 mg in luteal phase daily dosing and with 90 mg 2 and 1 weeks prior to menses. Fluoxetine is generally a well-tolerated treatment for PMDD and discontinuation effects have not been reported with intermittent dosing regimens.     

溴隐亭在120例泌乳素水平正常的不孕症患者促排卵治疗中的辅助作用观察

目的:探讨溴隐亭在泌乳素水平正常的不孕症患者促排卵治疗中的辅助作用。方法:不孕症患者120例,以随机抽样法分为对照组(60例)与治疗组(60例)。对照组于月经周期第5 d开始口服枸橼酸氯米酚50 mg.d-1,共5 d;月经周期第9 d开始B超监测卵泡发育情况并测量子宫内膜厚度,当优势卵泡直径达到18 mm时,加用人绒毛膜促性腺激素10 000 IU诱发排卵。治疗组除上述治疗外于月经周期第1 d开始口服溴隐亭1.25 mg.d-1,若妊娠则停药,未妊娠则连续服用3个月。结果:对照组排卵期子宫内膜厚度平均为(7.3±1.7)mm,治疗组为(10.3±2.1)mm,差异有统计学意义(P<0.05)。对照组第1、2、3个月获得妊娠分别为6、4、4例,妊娠率为23%(14/60),先兆流产发生率为42%(6/14);治疗组第1、2、3个月获得妊娠分别为14、10、6例,妊娠率为50%(30/60),先兆流产发生率为26%(8/30),差异有统计学意义(P<0.05)。结论:溴隐亭联合枸橼酸氯米酚用于泌乳素水平正常的不孕症患者,可提高其妊娠率,疗效显著。     

Pharmacotherapy of premenstrual syndromes and premenstrual dysphoric disorder: current practices

Premenstrual syndromes (PMS) and especially premenstrual dysphoic disorder (PMDD) affect a large segment of the population of women of reproductive age. Treatment is necessary in approximately 2-10% of women with PMS and PMDD because of the degree of impairment and distress experienced. Treatment modalities are increasingly based on hypotheses concerning possible underlying biological mechanisms: mostly ovulation-related hormonal changes and serotonergic abnormalities. Two treatment modalities distinguish themselves as highly effective: suppression of ovulation and specific serotonin re-uptake inhibitor (SSRI) antidepressants. Suppression of ovulation is effective for a wide range of PMS, while SSRIs are effective for PMDD with some degree of efficacy for physical symptoms. The SSRIs are also efficacious when administered intermittently--only during the luteal phase of the menstrual cycle.     

伊托必利联合复方丹参片治疗糖尿病胃病的效果分析

目的：观察伊托必利联合复方丹参片治疗糖尿病胃病的临床效果。方法将98例糖尿病胃病患者随机分为对照组（44例）和观察组（54例）,对照组仅口服伊托必利50 mg,3次/d;观察组口服伊托必利50 mg,3次/d,复方丹参片3片,3次/d;两组疗程均为4周,比较治疗前后两组临床症状改善情况。结果观察组治疗后临床症状评分低于对照组,差异有统计学意义（P＜0.05）。观察组治疗总有效率为94.4%,高于的对照组为68.2%,差异有统计学意义（P＜0.05）。结论伊托必利联合复方丹参片治疗糖尿病胃病效果显著,具有重要的临床应用价值。     

Female hormones affect symptom severity in obsessive-compulsive disorder

There is circumstantial evidence that reproductive events can influence symptom severity of obsessive-compulsive disorder (OCD). We sent self-report questionnaires to 350 female outpatients with OCD to examine the relationship between the menstrual cycle, pregnancy, menopause, hormonal contraceptives, selective serotonin reuptake inhibitors and symptom severity of OCD. Yale-Brown Obsessive-Compulsive Scale scores were used at three serial time points during the menstrual cycle to assess symptom severity. One hundred and one out of 350 questionnaires (29%) were returned and completed. Forty-nine patients reported an exacerbation of OCD symptoms during the premenstrual period, nine during the menopause and 17 patients during pregnancy, whereas 11 patients mentioned improvement of OCD symptoms during pregnancy. Premenstrual dysphoric disorder could only partly explain a premenstrual exacerbation of OCD symptoms. Exacerbation of OCD could be related to reproductive events in a considerable number of patients, especially the premenstrum. Because reproductive cycle events influence the symptom severity of OCD, the menstrual cycle should be taken into account when assessing the severity of OCD symptoms during pharmacological studies.     

Pharmacotherapy of premenstrual syndromes and premenstrual disphoric disorder: current practices

Premenstrual syndromes (PMS) and especially premenstrual dysphoic disorder (PMDD) affect a large segment of the population of women of reproductive age. Treatment is necessary in ~ 2 - 10% of women with PMS and PMDD because of the degree of impairment and distress experienced. Treatment modalities are increasingly based on hypotheses concerning possible underlying biological mechanisms: mostly ovulation-related hormonal changes and serotonergic abnormalities. Two treatment modalities distinguish themselves as highly effective: suppression of ovulation and specific serotonin re-uptake inhibitor (SSRI) antidepressants. Suppression of ovulation is effective for a wide range of PMS, while SSRIs are effective for PMDD with some degree of efficacy for physical symptoms. The SSRIs are also efficacious when administered intermittently - only during the luteal phase of the menstrual cycle.     

Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder

This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI.     

Therapeutic management of premenstrual syndrome

Importance of the field: Premenstrual syndrome (PMS) is among the most common health problems reported by reproductive-age women. Estimates indicate that up to 25% of women may warrant treatment for the distress or impaired functioning associated with the symptoms.

Areas covered in this review: The primary focus of this review is the clinical condition of PMS and randomized, placebo-controlled trials of PMS treatment. A literature search in PubMed was conducted for these topics. The most recent reports of specific treatments in controlled treatment studies and all meta-analyses were selected.

What the reader will gain: Reports consistently indicate that serotonergic antidepressants reduce PMS symptoms compared to a placebo. Hormonal treatments are the most widely prescribed medical treatment. Some oral contraceptives and gonadotropin-releasing hormone analogs have demonstrated efficacy, particularly for women who want contraception and PMS symptom control. Numerous non-pharmacologic treatments are utilized, but efficacy is reported only for calcium supplements, Vitex agnus castus (chasteberry), and cognitive–behavioral therapies. Further research to develop new therapies for the 40% of women with PMS who do not respond to the currently available treatments is needed.

Take home message: There are treatments with demonstrated efficacy for PMS, and the majority of women can be helped.     

雷贝拉唑联合莫沙必利治疗反流性食管炎临床观察

目的探讨雷贝拉唑联合莫沙必利治疗反流性食管炎的近期疗效和安全性。方法将经确诊的反流性食管炎患者110例随机分成治疗组55例和对照组55例,治疗组雷贝拉唑10mg,早晚各1次,餐前服用;莫沙必利5mg,3次／a,餐前半小时服用。对照组奥美拉唑20mg,1次／a,餐前服用;莫沙必利服用方法同上。两组治疗6周,观察临床疗效和安全性。结果治疗组总有效率（94．5％）显著高于对照组,（76．4％）,（P〈0．05）。结论雷贝拉唑联合莫沙必利治疗反流性食管炎临床症状改善迅速,临床疗效优于奥美拉唑联合莫沙必利。     

定眩汤治疗老年性眩晕的临床观察

目的 探讨定眩汤治疗老年性眩晕的临床效果.方法 选取老年性眩晕患者90例,分为对照组40例与观察组50例.对照组采用西医治疗,口服甲磺酸倍他司汀片,12 mg/次,3次/d;观察组采用中医治疗,定眩汤水煎服,每日1剂,分2～3次服用.两组均以15d为1个疗程,治疗后观察两组的临床疗效,比较治疗前后两组症状评分的变化.结果 观察组总有效率为90.0％,对照组总有效率为80.0％,两组比较,差异有统计学意义（P＜0.05）.治疗后,观察组症状评分为（1.02±0.21）分,较治疗前的（2.68±0.46）分明显降低（P＜0.05）;对照组症状评分为（2.01±0.43）分,较治疗前的（2.79±0.52）分明显降低（P＜0.05）;观察组症状评分低于对照组（P＜0.05）.结论 定眩汤治疗老年性眩晕效果显著,可明显改善患者的临床症状,值得推广应用.