Vasomotor Symptoms In Women Research Articles

Joint modeling of zero-inflated panel count and severity outcomes.

Panel counts are often encountered in longitudinal, such as diary, studies where individuals are followed over time and the number of events occurring in time intervals, or panels, is recorded. This article develops methods for situations where, in addition to the counts of events, a mark, denoting a measure of severity of the events, is recorded. In many situations there is an association between the panel counts and their marks. This is the case for our motivating application that studies the effect of two hormone therapy treatments in reducing counts and severities of vasomotor symptoms in women after hysterectomy/ovariectomy. We model the event counts and their severities jointly through the use of shared random effects. We also compare, through simulation, the power of testing for the treatment effect based on such joint modeling and an alternative scoring approach, which is commonly employed. The scoring approach analyzes the compound outcome of counts times weighted severity. We discuss this approach and quantify challenges which may arise in isolating the treatment effect when such a scoring approach is used. We also show that the power of detecting a treatment effect is higher when using the joint model than analysis using the scoring approach. Inference is performed via Markov chain Monte Carlo methods.

Extended-release oxybutynin therapy for vasomotor symptoms in women: a randomized clinical trial.

Assess effects of once-daily, extended-release oxybutynin chloride on frequency and severity of vasomotor symptoms in healthy, postmenopausal symptomatic women. A 12-week, multicenter, double-blind, placebo-controlled, phase 2 clinical trial randomized naturally postmenopausal women experiencing at least seven moderate-to-severe vasomotor symptoms daily to oxybutynin 15 mg once daily (n = 73) or placebo (n = 75). Co-primary outcomes were the change from baseline to week 12 in the frequency and severity of moderate-to-severe vasomotor symptoms. Significant reductions in both frequency and severity of moderate-to-severe vasomotor symptoms in women who received oxybutynin compared with placebo were observed at all weeks of treatment (P ≤ 0.007, all time points) through week 12. Mean changes in frequency in the oxybutynin and placebo groups were -9.48 and -4.69 episodes/d, respectively, at week 12. Mean changes in severity (scale 0-3) in the oxybutynin and placebo groups were -1.27 and -0.30, respectively, at week 12. At the end of treatment, 73% of women in the oxybutynin group and 26.1% in the placebo group rated symptom improvement "much better" (P ≤ 0.001). Women treated with oxybutynin showed significant improvement in sleep quality, sleep disturbance, and the global sleep index on the Pittsburgh Sleep Quality Index (P ≤ 0.023). Dry mouth was reported by 52.1% of participants given oxybutynin and 5.3% of participants given placebo, leading to discontinuation of oxybutynin in 6.8% of participants. Oxybutynin is an effective, nonhormonal therapy for moderate-to-severe vasomotor symptoms in postmenopausal women.

Abstract P3-12-02: Lifestyle interventions combined with acupuncture-like transcutaneous electrical nerve stimulation in managing vasomotor symptoms induced by breast cancer treatment: Results of a phase 2 randomized controlled trial

Abstract Background: Women with breast cancer can experience significant treatment induced vasomotor symptoms (TIVS). Non-hormonal strategies for TIVS (e.g. acupuncture, Venlafaxine) provide some relief but may be intolerable because of the invasive nature of the treatment and possible side effects. As such, women often prefer lifestyle strategies (LS) that can be self-administered. Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) is a non-invasive needleless technique that uses specific electrical parameters to stimulate selected acupoints to achieve clinical response with minimal toxicity. ALTENS can be administered with minimal training. It is amenable to quality assurance and can allow for self treatment by women. This study aimed to evaluate the efficacy of ALTENS in addition to LS in relieving TIVS in women with breast cancer. Methods: Eligible subjects were postmenopausal women with Stages 0-3 breast cancer who had completed cancer treatment and were experiencing hot flashes for ≥ one month with a Hot Flash Score (HFS) ≥15 in one week prior to consent. Anti-estrogen therapy was permitted. Non-hormonal drug therapies were prohibited. Subjects were randomized to either LS (control) or LS with concurrent ALTENS (combined). LS consisted of standardized lifestyle strategies (e.g. environmental control, managing hot flash triggers) counseling delivered by a specially trained nurse practitioner at week 0 with reinforcing counseling at weeks 12 and 24. ALTENS was given twice weekly for 12 treatments over an 8-week period. The HFS, Hot Flash Related Daily Interference Scale and the Short Form version 2 health survey were administered at weeks 0, 12 and 24. Heart rate variability was measured at weeks 0 and 12. The primary study endpoint was the number of responders, defined as women who had > 50% reduction in their HFS between weeks 0 and 12. Results: 71 eligible subjects with a median age of 52 (range: 40-87) were randomized to combined arm (n=36) and control (n=35). At 12 weeks there were 11 (30.6%) responders in the combined arm versus 2 (5.7%) in the control (p=0.012).The results at 24 weeks were 14 versus 4, respectively (p=0.013). Arms were balanced for anti-estrogen use. Two subjects chose to discontinue ALTENS after experiencing symptoms improvement. There were no serious adverse events. Conclusion: ALTENS in combination with lifestyle strategies is a promising non-pharmacologic approach that showed improvement in managing treatment induced vasomotor symptoms in women with breast cancer. Our trial results support its evaluation in phase 3 studies. Citation Format: Margaret Forbes, Raimond Wong, Stephen M Sagar, Jim A Julian, Mark N Levine, Joseph Hayward. Lifestyle interventions combined with acupuncture-like transcutaneous electrical nerve stimulation in managing vasomotor symptoms induced by breast cancer treatment: Results of a phase 2 randomized controlled trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-02.

Telesna dejavnost in zdravje žensk v pomenopavzi

Uvod: Kot posledica pomanjkanja estrogenov se po menopavzi pojavi večja verjetnost nastanka kardiovaskularnih bolezni, osteoporoze, depresije in urinske inkontinence. Namen članka je pregled literature in predstavitev rezultatov raziskav, ki so proučevale vpliv telesne dejavnosti na kardiovaskularni in vazomotorni sistem, na urogenitalno in vezivno tkivo ter na duševno zdravje pri ženskah v pomenopavzi. 
 Metode: Iskanje strokovne in znanstvene literature je bilo opravljeno s pomočjo bibliografskih baz podatkov COBISS.SI, PubMed, CINAHL, EMBASE in registra študij Cochrane Library. Iskanje je bilo omejeno na besedila, dostopna na spletu, v slovenščini ali angleščini (ali drugih jezikih, če so članki vsebovali izvlečke v angleščini), izdana od januarja 2000 do decembra 2012. Glede na vključitvene in izključitvene kriterije je bilo v pregled zajetih enajst randomiziranih kontroliranih raziskav, ki so bile glede na tematiko razdeljene v pet skupin. 
 Rezultati: Pokazal se je pozitiven vpliv redne telesne dejavnosti na izražanje simptomov, ki so posledica pomanjkanja estrogena v telesu žensk v pomenopavzi. Redna telesna dejavnost ima najboljši vpliv na kardiovaskularni sistem, mentalno zdravje, urinsko inkontinenco in osteoporozo, glede njenega vpliva na izražanje vazomotornih simptomov pa so mnenja deljena. 
 Diskusija in zaključek: Najkoristnejša telesna dejavnost za zdravje žensk v pomenopavzi je aerobna vadba zmerne intenzitete. Potrebne so nadaljnje raziskave o vplivu telesne dejavnosti na izražanje vazomotornih simptomov pri ženskah v pomenopavzi.

Effects of stellate ganglion block on vasomotor symptoms

Uncontrolled intervention studies, including studies involving breast cancer survivors, have demonstrated improvements in vasomotor symptoms (VMS) after stellate ganglion blockade (SGB) with a local anesthetic. This study presents the first randomized sham-controlled trial of SGB for the treatment of VMS. Participants included 40 postmenopausal women, aged 30 to 70 years, with moderate to severe VMS. The study was a randomized sham-controlled trial comparing the effects of SGB versus sham injection on the frequencies of total and moderate to severe VMS, as measured by daily diaries. Image-guided SGB was performed with 5 mL of 0.5% bupivacaine. Sham injection of saline was performed in subcutaneous tissues in the neck. VMS were recorded at baseline and for 6 months thereafter. Objective VMS were recorded using ambulatory sternal skin conductance monitoring during a 24-hour period at baseline and on 3-month follow-up. There were no significant group differences in overall VMS frequency, but the frequency of moderate to very severe VMS was reduced more in the active group compared with the sham treatment group (event rate ratio, 0.50; 95% CI, 0.35-0.71; P < 0.001). The frequency of objective VMS was also reduced to a greater degree in the SGB group than in the sham group (event rate ratio, 0.71; 95% CI, 0.64-0.99; P < 0.05). There were no study-related serious adverse events. SGB may provide effective treatment of VMS in women who seek nonhormonal treatments because of safety concerns and personal preference. The finding that SGB significantly reduces objectively measured VMS provides further evidence of efficacy. A larger trial is warranted to confirm these findings.

New pharmacological therapies for vasomotor symptom management: focus on bazedoxifene/conjugated estrogens and paroxetine mesylate.

To review 2 recently approved therapies for vasomotor symptoms (VMSs) of menopause. PubMed searches (June 2003 to May 2014) were conducted using the keywords paroxetine vasomotor and bazedoxifene vasomotor. References from relevant articles were reviewed for pertinent citations that were not identified in the PubMed search. Phase 3 clinical trials of recently approved hormonal and nonhormonal therapies for the treatment of VMSs of menopause were selected. Studies that evaluated the use of paroxetine mesylate or bazedoxifene (BZA)/conjugated estrogens (CEs) for VMSs were included. Four studies for BZA/CEs were identified. One published report of low-dose paroxetine mesylate was identified that was a combined analysis of 2 phase 3 studies. Both agents significantly decrease the incidence of hot flushes compared with placebo and are approved for the treatment of moderate to severe VMSs associated with menopause. BZA/CEs is only approved for women with an intact uterus. In all circumstances, the use of BZA/CEs should be limited to the shortest duration possible. Paroxetine mesylate was not studied head-to-head against hormone therapy, but the magnitude of its effect on VMSs is less than expected with hormone therapy. BZA/CEs is an effective hormonal therapy for treating VMSs in women with an intact uterus. Paroxetine mesylate is the first nonhormonal therapy that the FDA has approved for VMSs, making both viable options for the treatment of VMSs of menopause.

Aerobic exercise as a treatment for vasomotor menopausal symptoms: Randomised controlled trial protocol

BackgroundEvidence suggests that a high proportion of perimenopausal and postmenopausal women experience vasomotor symptoms (hot flushes/night sweats) that can be severe and disruptive and which are the principal reason for seeking medical intervention. Hormone therapy (HT) is known to be an effective treatment for troublesome hot flushes/night sweats but research has raised questions about the safety of HT and there have been negative high profile media reports about its use. Consequently many women are seeking alternatives and exercise might be one such option but there is a lack of high quality evidence on its effectiveness. AimsThis RCT initially aims to investigate the feasibility/acceptability of two exercise interventions identified from our previous preference study in 165 women, and if found to be feasible/acceptable, continue to recruit sufficient women (n=261) to examine the effect of these interventions on hot flushes/night sweats and other outcomes relevant to menopausal women. MethodWe aim to recruit inactive perimenopausal and menopausal symptomatic women not using HT and randomise them to one of two exercise interventions or usual care for six months. ResultsWe will assess outcomes at baseline and 6 and 12 months from randomisation. ConclusionWe hope this RCT will contribute towards increasing the evidence regarding the question of whether exercise is an effective treatment for vasomotor symptoms in women not taking HT.

The Hormonal Profile of Norethindrone Acetate: Rationale for Add-Back Therapy With Gonadotropin-Releasing Hormone Agonists in Women With Endometriosis

Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.

Cardiovascular and Metabolic Effects of Medroxyprogesterone Acetate versus Conjugated Equine Estrogen After Premenopausal Hysterectomy with Bilateral Ovariectomy

To compare the cardiovascular and metabolic effects of medroxyprogesterone acetate (MPA) with those of conjugated equine estrogen (CEE) as single-hormone therapies in women who underwent hysterectomy with bilateral ovariectomy. Secondary analysis of a 12-month, double-blind, randomized, parallel-therapy trial. Four teaching hospitals and one community hospital in Vancouver, Canada. Thirty-three healthy women who underwent premenopausal hysterectomy with bilateral ovariectomy. Subjects received either MPA 10 mg/day (18 women) or CEE 0.6 mg/day (15 women) for 12 months, started immediately after hysterectomy with bilateral ovariectomy. Lipid profiles (high-density lipoprotein cholesterol [HDL], total cholesterol, apolipoprotein B, and triglyceride levels), homeostatic measures (hemoglobin A(1c) and fasting blood glucose level), hormone levels (free and bioavailable testosterone, cortisol, sex hormone-binding globulin [SHBG], and dehydroepiandrosterone sulfate), inflammatory markers (C-reactive protein [CRP] and serum albumin levels), and anthropometric measures (body mass index [BMI], truncal fat, and total body fat) were assessed over the 12-month period. After 12 months, the women assigned to MPA had lesser increases in BMI (p=0.04), triglyceride (p=0.003), HDL (p<0.0005), SHBG (p<0.0005), total testosterone (p=0.003), and CRP values (p=0.01) and higher serum albumin levels (p<0.0005) compared with the women receiving CEE. Therapy with CEE, but not MPA, after surgical menopause appears to predispose healthy women to low-grade inflammation, as evidenced by its independent associations with elevated CRP and reduced albumin levels. In women treated with MPA, the favorable levels of inflammatory markers, BMI, and triglyceride levels need to be confirmed in larger controlled trials, as progesterone therapy may provide a safe and effective alternative to estrogen for vasomotor symptoms in women with surgical menopause.

Ethnic Differences in Vasomotor Symptoms of Women

Ethnic Differences in Vasomotor Symptoms of Women

Identifying meaningful differences in vasomotor symptoms among menopausal women

First, to identify treatment satisfaction thresholds for interpreting treatment-related changes in vasomotor symptoms, and, second, to determine the doses of desvenlafaxine (DVS) (administered as desvenlafaxine succinate) that effectively provide relief of vasomotor symptoms considered important by menopausal women. Efficacy and treatment satisfaction were assessed in 620 postmenopausal women with moderate to severe vasomotor symptoms participating in a double-blind, placebo-controlled trial and randomly assigned to placebo or 50, 100, 150, or 200 mg DVS. Number and severity of hot flushes and number of nighttime awakenings were recorded in daily diaries for 12 weeks of treatment. At week 12, responses to the Menopause Symptoms Treatment Satisfaction Questionnaire were compared with efficacy results. Greater percentages of participants in the DVS groups reported being "satisfied" or "extremely satisfied" with daytime and nighttime control of hot flushes compared with placebo. The treatment satisfaction threshold, defined as the difference between the average reduction in vasomotor symptoms for women who were "neutral" versus "satisfied," was 1.64 for moderate to severe hot flushes and 0.42 for nighttime awakenings. Statistically significant reductions with 100, 150, and 200 mg DVS exceeded treatment satisfaction threshold results for at least one of these thresholds, and results with 100 mg DVS compared with placebo exceeded both treatment satisfaction thresholds. Among menopausal women with moderate to severe vasomotor symptoms, the treatment satisfaction thresholds that were meaningful to participants were 1.64 fewer moderate to severe hot flushes per day and 0.42 fewer nighttime awakenings per night. A dose of 100 mg DVS met both of these important vasomotor symptom change thresholds.

Long-term follow-up of acupuncture and hormone therapy on hot flushes in women with breast cancer: a prospective, randomized, controlled multicenter trial

Objective To evaluate the effects of electro-acupuncture (EA) and hormone therapy (HT) on vasomotor symptoms in women with a history of breast cancer.Methods Forty-five women were randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months. The number of and distress caused by hot flushes were registered daily before, during and up to 24 months after start of treatment.Results In 19 women who completed 12 weeks of EA, the median number of hot flushes/24 h decreased from 9.6 (interquartile range (IQR) 6.6–9.9) at baseline to 4.3 (IQR 1.0–7.1) at 12 weeks of treatment (p < 0.001). At 12 months after start of treatment, 14 women with only the initial 12 weeks of EA had a median number of flushes/24 h of 4.9 (IQR 1.8–7.3), and at 24 months seven women with no other treatment than EA had 2.1 (IQR 1.6–2.8) flushes/24 h. Another five women had a decreased number of flushes after having additional EA. The 18 women with HT had a baseline median number of flushes/24 h of 6.6 (IQR 4.0–8.9), and 0.0 (IQR 0.0–1.6; p = 0.001) at 12 weeks.Conclusion Electro-acupuncture is a possible treatment of vasomotor symptoms for women with breast cancer and should be further studied for this group of women.

Treatment of vasomotor symptoms in the menopausal transition and postmenopausally: psychiatric comorbidity

This article aims to educate the nonpsychiatric as well as the psychiatric clinician on the impact of vasomotor symptoms in women with comorbid psychiatric problems and the challenges of treating vasomotor symptoms in these women. The pathophysiology, prevalence and common risk factors associated with disturbing hot flashes in the menopausal transition are reviewed. Hormonal, nonhormonal and behavioral treatment options of vasomotor symptoms for these women are discussed. Special pharmacokinetic implications for hormonal treatment of those women on anticonvulsant medications for the treatment of their mood disorders, on tamoxifen and/or with high or low sex hormone-binding globulin are examined. An in-depth discussion of mood and the menopausal transition, theoretical mechanisms for mood problems with the symptomatic menopause and the impact of stress on the symptomatic menopause are found elsewhere in this clinical review series on psychiatric illness, stress and the symptomatic menopause.

Physical activity and risk of vasomotor symptoms in women with and without a history of depression

To examine whether physical activity was associated with decreased risk of vasomotor symptoms in a prospective study of women transitioning through menopause. Hypotheses were evaluated in the Harvard Study of Moods and Cycles, a longitudinal study of women with and without a history of major depression (N = 523). Ordinal logistic regression models were utilized to assess the odds of vasomotor symptoms (none, mild, moderate/severe; Greene Climacteric Scale) associated with physical activity (quartiles of metabolic equivalent-hours per week) at study enrollment and over a 3- to 5-year follow-up period. No significant associations between physical activity and vasomotor symptoms were observed for the sample as a whole. However, exploratory analyses stratified by depression history revealed that among the 157 women with a lifetime history of major depression, high (odds ratio [OR] = 0.28, 95% CI: 0.09-0.83) or moderately high (OR = 0.33, 95% CI: 0.11-0.99) physical activity proximal to the vasomotor assessment, as well as consistently high (OR = 0.27, 95% CI: 0.10-0.75) or increasing (OR = 0.33, 95% CI: 0.12-0.92) physical activity over the duration of the 3- to 5-year follow-up period was associated with decreased vasomotor symptoms relative to sedentary behavior. No significant associations were observed for women without a history of depression. Physical activity may be associated with decreased risk of vasomotor symptoms among women with a history of major depression.

The Relationship of Longitudinal Change in Reproductive Hormones and Vasomotor Symptoms during the Menopausal Transition

The relationship of reproductive hormones to vasomotor symptoms (VMS) has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65-76% of women traversing the menopausal transition and are a primary reason for medical intervention during this life stage. The purpose of this report was to relate longitudinal serum concentrations of the reproductive hormones estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), and SHBG and the free hormone indices free E2 index (FEI) and free T index (FTI) with the occurrence of VMS in women traversing the menopausal transition. The Study of Women's Health Across the Nation is a multisite, longitudinal, cohort study of the menopausal transition being conducted in community-based groups of women. At baseline, 3302 menstruating women who belonged to one of five ethnic/racial groups were recruited and followed up with annual visits. Frequencies of symptoms (hot flashes, night sweats) for the prior 2 wk and measures of other covariates as well as potentially confounding variables were self-reported in the annual interview. Serum was obtained annually, on d 2-5 of a spontaneous cycle in cycling women or within 90 d of the anniversary of the baseline study visit in noncycling women and assayed for FSH, E2, T, SHBG, and DHEAS. FTI and FEI were calculated. This analysis incorporated available longitudinal data from 3293 women, excluding information collected at or after first report of hormone therapy use or hysterectomy. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. After adjusting for age, body mass index, and other related covariates, VMS prevalence increased with higher (log)FSH concentrations, and the increase was greater when blood was drawn more than 5 d after menses began. FSH concentrations were positively associated with the frequency of either hot flashes or night sweats, and higher FSH concentrations were associated with greater odds of reporting more frequent symptoms. Vasomotor symptom prevalence decreased with higher (log)E2, (sqrt)SHBG, and (log)FEI but only when these hormone values were modeled independently of (log)FSH values and the specimens were obtained outside the d 2-5 window. When modeled simultaneously with (log)FSH, (log)E2, (sqrt)SHBG, and (log)FEI were no longer significantly associated with symptom prevalence. (Cubic root)T and (sqrt)DHEAS concentrations and (log)FTI were not associated with the prevalence of VMS. Annual serum FSH concentrations, but not E2, T, DHEAS, FTI, or FEI when collectively modeled longitudinally, are associated with both the prevalence and frequency of VMS in women at midlife.

Vasomotor symptoms decrease in women with breast cancer randomized to treatment with applied relaxation or electro-acupuncture: a preliminary study

Objective To evaluate the effect of applied relaxation and electro-acupuncture on vasomotor symptoms in women treated for breast cancer.Methods Thirty-eight postmenopausal women with breast cancer and vasomotor symptoms were randomized to treatment with electro-acupuncture (n = 19) or applied relaxation (n = 19) during 12 weeks. The number of hot flushes was registered daily in a logbook before and during treatment and after 3 and 6 months of follow-up.Results Thirty-one women completed 12 weeks of treatment and 6 months of follow-up. After 12 weeks of applied relaxation, the number of flushes/24 h had decreased from 9.2 (95% confidence interval (CI) 6.6–11.9) at baseline to 4.5 (95% CI 3.2–5.8) and to 3.9 (95% CI 1.8–6.0) at 6 months follow-up (n = 14). The flushes/24 h were reduced from 8.4 (95% CI 6.6–10.2) to 4.1 (95% CI 3.0–5.2) after 12 weeks of treatment with electro-acupuncture and to 3.5 (95% CI 1.7–5.3) after 6 months follow-up (n = 17). In both groups, the mean Kupperman Index score was significantly reduced after treatment and remained unchanged 6 months after end of treatment.Conclusion We suggest that applied relaxation and electro-acupuncture should be further evaluated as possible treatments for vasomotor symptoms in postmenopausal women with breast cancer.

Estrogenic control of thermoregulation in ERαKO and ERβKO mice

Objective Estrogen is the most effective treatment for preventing the vasomotor symptoms in women. The ability of estrogen to control tail skin temperature (TST) in rats is used as an animal model for the studies of estrogens on menopausal hot flushes. Today, we know that estrogen can mediate its actions via the interaction with two different estrogen receptors: ERα and ERβ. To elucidate the function of each estrogen receptor subtype control of thermoregulation, we developed an animal model demonstrating estrogen control of TST in mice. Methods and results We determined that estrogen depletion by ovariectomy (OVX) of mice causes an elevation of basal tail skin temperature. Administration of estradiol cypionate suppressed this increase in TST in a dose dependent manner. Estrogen depletion by OVX in either ERα-knockout (ERαKO) or ERβ-knockout (ERβKO) mice resulted in an increase in TST that could be suppressed by estrogen treatment. Conclusion We show that mice serve as a suitable animal model for estrogen-controlled thermoregulation and that the expression of either ERα or ERβ alone in mice is sufficient to maintain control TST by estrogen.

Venlafaxine in the treatment of depressive and vasomotor symptoms in women with perimenopausal depression

Perimenopause is often marked by vasomotor symptoms and dysphoria. Antidepressant studies have demonstrated decreased frequency and severity of hot flashes in breast cancer survivors and menopausal women. We hypothesized that venlafaxine would relieve both depressive and vasomotor symptoms in depressed perimenopausal women. Sixteen women fulfilling clinical criteria for climacteric phase and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for a depressive episode were enrolled in an open-label 8-week trial of extended-release venlafaxine. Depressive and climacteric symptoms were monitored using the Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A), Clinical Global Impression (CGI) scale, and Greene Climacteric Scale (GCS). Serum follicular stimulating hormone (FSH) and estradiol concentrations were monitored. Significant decreases in Ham-D and Ham-A scores and the GCS psychiatric subscale were seen after 2 weeks of treatment. In an intention-to-treat analysis, 81% of the subjects demonstrated a therapeutic antidepressant response (>50% decline in Ham-D score) and 75% achieved clinical remission (Ham-D score < or =7) after 8 weeks of venlafaxine therapy (75-225 mg/day). Total GCS scores declined 60%, and GCS vasomotor subscores decreased among those with vasomotor symptoms at baseline. These data suggest that venlafaxine treatment improves overall well-being, reduces depressive symptoms, and may diminish baseline vasomotor symptoms in depressed perimenopausal women. Further studies are warranted to investigate the utility of venlafaxine in perimenopausal depression.

The relationship of longitudinal change in reproductive hormones and vasomotor symptoms across the menopausal transition

The relationship of reproductive hormones to vasomotor symptoms has been incompletely explored, although an increase in such symptoms at midlife and a reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65–76% of women traversing the menopausal transition and are a primary reason for medical intervention during this lifestage. The purpose of this report is to relate serum concentrations of the reproductive hormones estradiol (E2), follicle stimulating hormone (FSH), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) and the free hormone indices FEI and FTI with the occurrence of vasomotor symptoms in women traversing the menopausal transition. SWAN is a multi-site, longitudinal, observational cohort study of the menopausal transition being conducted in community-based groups of women. At baseline, 3302 menstruating women who belonged to one of 5 ethnic/racial groups were recruited and followed at an annual visit. Frequencies of symptoms (hot flashes, cold sweats, night sweats, vaginal dryness, leaking urine, heart pounding or racing, headache, and/or stiffness or soreness) for the prior two weeks were self-reported in the annual interview as well as measures of potentially confounding variables. Serum was obtained annually, on days 2–5 of a spontaneous cycle in cycling women or within 90 days of the anniversary date in non-cycling women, and assayed for FSH, E2, T, SHBG and DHEAS. FTI and FEI were calculated. This analysis includes data from 3293 women with a serum hormone value and available vasomotor symptom data from at least one longitudinal visit: baseline, first, second, third, and/or fourth annual follow-up. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. Vasomotor symptom prevalence increased with increasing logFSH, and this increase was greater when specimens came from outside the day 2–5 window. There was a 29% increase in the overall likelihood of reporting any vasomotor symptoms for each unit increase in serum LogFSH, and a greater increase in women without menses for at least 3 months (OR=1.58). Vasomotor symptom prevalence decreased with increasing logE2 and logFEI, but only when specimens were obtained outside the day 2–5 window. There was a 12% decrease in the likelihood of reporting symptoms with each unit increase in serum logE2 in such samples. LogT and log DHEAS concentrations, and logFTI, were not associated with the prevalence of vasomotor symptoms. When modeled simultaneously with logFSH, logE2 was no longer significantly associated with symptom prevalence. FSH concentrations were positively associated with the frequency of reported hot flashes with a greater effect at higher hot flash frequencies. We conclude that, when modeled together longitudinally, FSH, but not E2, T, DHEAS, FTI or FEI, is positively associated with both the prevalence and frequency of vasomotor symptoms in women at midlife.

Transition From Estrogen–Progestin to Raloxifene in Postmenopausal Women

To compare vasomotor symptoms after transition from estrogen-progestin therapy to raloxifene 60 mg/d with and without a placebo washout. Postmenopausal women currently taking continuous combined estrogen-progestin therapy (conjugated equine estrogen, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg) daily for 5 or more months were enrolled. Women were randomized to 1 of 4 blinded regimens: 1) 12 weeks estrogen-progestin; 2) 12 weeks placebo; 3) 4 weeks placebo, then 8 weeks raloxifene; or 4) 12 weeks raloxifene. For the final 36 weeks, all subjects received raloxifene. Vasomotor symptoms were assessed by patient diaries. A total of 266 women (mean age 57.5) were enrolled. Mean hot flush frequency at baseline was approximately 1 per week in the entire population, with 16% of women reporting hot flushes. Mean frequency and severity of hot flushes during the first 12 weeks of the study were statistically greater in the 3 groups transitioned off estrogen-progestin (range of hot flushes per week: 4 weeks, 11-12; 8 weeks, 18-24; 12 weeks, 13-16), as compared with those continuing estrogen-progestin, with no difference between these 3 groups (P> or =.1). Approximately 50-70% of these women reported hot flushes, generally rated as mild to moderate by participants, after estrogen-progestin discontinuation. A large proportion of women discontinuing estrogen-progestin experience hot flushes. Raloxifene does not appear to increase the frequency or severity of vasomotor symptoms in women discontinuing estrogen-progestin more than that observed with placebo treatment after estrogen-progestin discontinuation. Transition from estrogen-progestin to raloxifene with no washout period therefore may be acceptable. I