[Clinical effects of hormone replacement therapy with estradiol valerate and cyproterone acetate in perimenopausal women]. Influence of a continuous combined HRT (2 mg estradiol valerate and 2 mg dienogest) on postmenopausal depression [Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension]. Effect of estrogen replacement therapy on symptoms of depression and anxiety in non-depressive menopausal women Effects of 5 years of hormonal replacement therapy on menopausal symptoms and blood pressure-a randomised controlled study. Evidence-based review of therapies at the menopause. Hormone replacement therapy use and menopausal symptoms among women participating in a behavioral lifestyle intervention. Health related quality of life after combined hormone replacement therapy: randomised controlled trial The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. [Hormone replacement therapy in breast cancer patients: a study of 230 patients, with a case-control study]. A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women. Hormonal and psychological treatment: therapeutic alternative for menopausal women? Hormonal treatment and psychological function during the menopausal transition: an evaluation of the effects of conjugated estrogens/cyclic medroxyprogesterone acetate. A comparison of the effect of estrogen with or without progesterone on mood and physical symptoms in postmenopausal women. Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women: Study of Women's Health Across the Nation Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS–Cognitive and Affective Study Estrogen replacement in perimenopause-related depression: a preliminary report.
BACKGROUND In perimenopause many women complain of psychogenic and organic disorders often connected with initial and increasing levels of hypoestrogenism . In this study we evaluated the effects of hormone replacement therapy ( HRT ) in symptomatic women in perimenopause . METHODS We enrolled 100 healthy and symptomatic women who were r and omly distributed to two groups for a 12-month study . Group A : 50 patients received HRT with estradiol valerate and cyproterone acetate ( Pausene(R ) ) ; Group B : 50 patients were used as a control group ( treated with Cacit Vitamin D30(R ) ) . A number of clinical and instrumental tests were performed at 0 , 6 and 12 months to evaluate any changes in vasomotor and urogenital symptoms , bone and serum homeostasis and possible sexual disorders . The statistical analysis was performed using the c2 test . RESULTS The group of women receiving HRT showed a significant reduction in vasomotor clinical symptoms ( p<0.001 ) and sexual disorders ( p<0.002 ) ; this was not reflected in the control group where libido decreased steadily with apparent slight improvements only at the end of the study . The urogenital disorders disappeared almost completely in Group A , whereas they diminished in Group B. HRT patients also showed a slight increase ( p<0.001 ) in the initial value of BMD ( bone mineral density ) , a reduction in the marker for bone turnover and an improved lipid profile ( p<0.05 ) . These changes were unfortunately not noted in Group B. CONCLUSIONS On the basis of these results we conclude that HRT appeared to have a beneficial effect on perimenopausal clinical symptoms over the 12-month period , leading to marked improvements in the psychophysical wellbeing of symptomatic women in perimenopause Objective This r and omized , double-blind , placebo-controlled study was planned to investigate the effects of continuous combined hormone replacement therapy ( HRT ) with 2 mg estradiol valerate and 2 mg dienogest ( Climodien ® /Lafamme ® ) over 24 weeks on postmenopausal depression . Method A total of 129 patients with a mild to moderate depressive episode according to ICD-10 : F32.0 , F32.1 in the context of a postmenopausal syndrome ( ICD-10 : N95.1 ) and a baseline score in the Hamilton depression scale ( HAMD ) ⩾ 16 were included in the study . The primary target variable was depression severity as measured by the HAMD after 24 weeks of treatment . A four-point difference between HRT and placebo at the end of the study and , in addition , a final score ⩽ 8 ( corresponding to an improvement of ⩾ 50 % as compared to baseline ) for the individual patient ( responders analysis ) were considered clinical ly relevant . Clinical global impression ( CGI ) of investigators ( therapeutic and side-effects ) at the end of the study was investigated . Secondary effects of HRT  on depression severity caused by its effect on vasomotor symptoms or sleep disturbances ( domino hypothesis ) were taken into consideration . Also , the study addressed the question of whether the effect of HRT on depression severity depends on a history of premenstrual syndrome ( PMS ) or postnatal depression ( PND ) . Results The results showed a clear and clinical ly relevant reduction of depression severity  under HRT after 24 weeks of treatment and superiority over placebo ( p < 0.0005 ) in spite of a strong placebo effect . The effects of the estrogen – progestin combination thereby seemed only partially to be dependent on the improvement of vasomotor symptoms and sleep disturbances . Also , the effects of HRT could not be shown to be dependent on a history of PMS and /or PND , even though women with and without this history clearly differed in baseline depression scores ( p < 0.0001 ) . The assessment of CGI was positive : whereas HRT was clearly superior to placebo with regard to therapeutic effects ( p = 0.0014 ) , there were no differences with regard to side-effects ( p = 0.35 ) . Conclusion The combination of 2 mg estradiol valerate and 2 mg dienogest can be regarded as an effective and safe treatment option for women with mild to moderate depression in the context of postmenopausal syndrome AIM The effect of hormone replacement therapy ( HRT ) on the quality of life in women with hypertension is still not clear . Thus , the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of st and ardized question naires . MATERIAL AND METHODS The study population consisted of 53 women ( mean age 50.9 + /- 6.3 years ) with mild and moderate essential hypertension ( mean duration 6.4 + /- 6.4 years ) . The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml , accompanied by follicle-stimulating hormone ( FSH ) levels > 21 U/I. Twenty seven women were blindly r and omised to transdermal hormone replacement therapy ( HRT ) and received 17-beta-estradiol and noretisterone acetate , TTS .  Twenty six women were r and omly selected as controls . The subjects were evaluated at baseline ( after 2 weeks ' wash-out from hypotensive drug period ) and after three months of HRT using self-administered st and ardized quality of life question naires : the Psychological General Well-being Index ( PGWB ) and the Subjective Symptoms Assessment Profile ( SSA-P ) . RESULTS No differences were found in blood pressure values , heart rate , body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up . There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups . Similarly , the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline . After 3 months , a significant improvement in PGWB total score was observed in women receiving HRT . This effect was due to improvement in anxiety , positive well-being and vitality . Moreover , emotional distress , symptoms of flushing , sweating and trembling h and s also diminished and sexual capacity improved in women treated with HRT . CONCLUSION A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being , seems to decrease emotional tension , increase sexual capacity and markedly relieves some vasomotor symptoms The efficacy of estrogen replacement therapy ( ERT ) for mood disturbances associated with menopause has yet to be firmly established . The objective of this study was to investigate the efficacy of ERT for improving mood and anxiety of non-depressive postmenopausal women . This double-blind , r and omized , placebo-controlled study involved two treatment groups : one receiving conjugated equine estrogens ( CEEs ; 0.625 mg/day ) and the other placebo , for six cycles of 28 days each . Subjects were hysterectomized , healthy , non-depressive ( according to Schedule for Affective Disorders and Schizophrenia , Life Time Version [ SADS-L ] ) women .  Depressive and anxiety symptoms were assessed with the Beck Depression Inventory ( BDI ) , and the Hamilton Anxiety Scale ( HAMA ) , respectively . The Profile of Mood States ( POMS ) and other scales were used to characterize symptoms . In both groups , BDI scores were significantly lower at cycles 1 , 2 , 3 , and 6 , compared with baseline assessment s ( p < 0.01 ) . Anxiety scores for both groups significantly improved from cycle 3 to study endpoint . The only significant difference favoring the active group occurred at cycle 1 . POMS scores were significantly improved at the end of cycles 1 , 2 , 3 and 6 among treated subjects and at the end of cycles 2 , 3 , and 6 among placebo subjects . ERT is not associated with improvements in mood or anxiety symptoms in non-depressive , hysterectomized , postmenopausal women OBJECTIVES To study the effects of hormonal replacement on hot flushes , other symptoms linked to menopause , and blood pressure . METHODS The study included 1006 early postmenopausal women aged 45 - 58 years , participating in the Danish Osteoporosis Prevention Study ( DOPS ) r and omised to Hormonal replacement therapy ( HRT )  ( n=502 ) or no HRT  ( n=504 ) in an open label trial . Symptom scores were recorded at baseline , after 6 month , 1 , 2 , and 5 years on a modified Greene scale ( range 0 - 4 with 0 equalling no symptoms , and 4 maximal symptoms ) . RESULTS HRT efficiently alleviated hot flushes ( mean+/-S.E.M. score 0.48+/-0.04 in HRT vs. 0.83+/-0.05 in no HRT after 5 years , P<0.01 by repeated measures ANOVA ) , sleeping difficulties associated with hot flushes ( 0.21+/-0.60 vs. 0.37+/-0.86 , P<0.01 ) , vaginal dryness ( 0.45+/-0.04 vs. 0.73+/-0.05 , P<0.01 ) , dyspareunia ( 0.27+/-0.04 vs. 0.39+/-0.04 , P<0.01 ) , and libido ( 0.48+/-0.05 vs. 0.59+/-0.05 , P=0.08 ) . In the untreated group the occurrence of mood swings ( from 0.77+/-0.05 at baseline to 0.45+/-0.04 after 5 years , 2P<0.01 ) and oedemas ( from 0.59+/-0.04 to 0.43+/-0.04 , 2P=0.02 ) decreased with age while the occurrence of incontinence increased ( from 0.43+/-0.03 to 0.52+/-0.04 , 2P<0.01 ) . These changes were not influenced by HRT . Furthermore , HRT had no influence on presence of headache ( 0.54+/-0.05 vs. 0.58+/-0.05 after 5 years ) , voiding pattern ( 0.49+/-0.04 vs. 0.53+/-0.04 ) , or blood pressure ( mean systolic pressure 123+/-18 vs. 123+/-19 , diastolic pressure 77+/-10 vs. 77+/-11 ) . CONCLUSIONS HRT is efficient in controlling hot flushes and vaginal dryness , and symptoms related to these conditions . However , no effect on blood pressure or other menopause symptoms was recorded Background and Objective The highest level of scientific evidence available for each therapy for menopausal symptoms was sought , for example , systematic review s of r and omised controlled trials ( RCTs ) . Results There is reasonable evidence that some symptoms are modified by lifestyle , for example , cessation of smoking , exercise , reduction of alcohol , diet and alleviation of psychosocial stress . No complementary medicine , for example , phytoestrogens , black cohosh , herbal or homeopathic medicines or complementary therapies , for example , acupuncture , yoga , chiropractic manipulation , reflexology or magnetic devices have a greater effect than the usual placebo effect seen in quality blinded RCTs . Some have potential side-effects . So-called ' bioidentical hormones ' have no evidence -base and potential for harm . None of the above therapies have evidence of efficacy and long-term safety . Selective serotonin and noradrenaline re-uptake inhibitors ameliorate vasomotor symptoms and sometimes menopausal depression better than placebo . The most effective therapy for menopausal ( oestrogen ) deficiency symptoms is oestrogen which is the main component of hormone replacement therapies ( HRT ) . Compared with placebo HRT is highly effective in relieving hot flushes , night sweats , dry vagina and dyspareunia . It also improved joint pains , sexuality and sleeplessness and reduced subsequent fractures in RCTs . The increased risk of oral HRT for thromboembolism is small around menopause , for those without thrombotic risk factors , and is not elevated with non-oral routes . Cardiovascular disease may be reduced when HRT is initiated near menopause . Breast cancer risk increases after several years with the use of oral HRT containing progestogens at an annual rate of 8/10 000 ( < 0.1 % ) . No increase in breast cancer risk was seen with oestrogen-only HRT BACKGROUND The decision to take hormone replacement therapy ( HRT ) is a choice many women encounter when entering menopause . The purpose of this study was to examine the choice to take HRT while participating in a lifestyle intervention to reduce cardiovascular risk through the menopause . METHODS The Women 's Healthy Lifestyle Project is a r and omized clinical trial design ed to examine whether a behavioral lifestyle intervention can decrease the expected rise in cardiovascular risk through the menopause . Participants ( N = 535 ) completed question naires and were interviewed regarding menopausal symptoms , menopausal status , hot flashes , and  HRT  use at baseline and 54 months . RESULTS The intervention was successful in preventing risk elevation through the 54-month visit . At the final visit , there was no difference between the intervention and control groups in the percentage who had become postmenopausal ( 32.9 % vs 35.0 % , respectively ) , there was no difference between control and intervention with  HRT  use , with 31.2 % reporting use of HRT , and there was no difference between groups with menopausal symptoms . The women started HRT an average of 6 months after they missed a period . Baseline risk factors did not predict HRT use at the 54-month visit . CONCLUSIONS A sizable number of women reported HRT use . The decision to use HRT was not influenced by the lifestyle intervention or their baseline cardiovascular risk , and these women started HRT very early in the peri- to postmenopause . Further , weight loss in the perimenopause did not affect menopausal symptoms Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Menopause impacts 25 million women world wide each year , and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030 . Menopause has been associated with symptoms of hot flashes , night sweats , dysphoric mood , sleep disturbance , and conditions of cardiovascular disease , depression , osteoporosis , osteoarthritis , depression , dementia , and frailty . Conventional hormone replacement therapy results in increased thrombotic events , and an increased risk of breast cancer and dementia as evidence d in large prospect i ve clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women 's Health Initiative . A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors . Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile , yet long-term studies of this treatment model are lacking . The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol , estradiol , progesterone , DHEA , and testosterone on cardiovascular biomarkers , hemostatic , inflammatory , immune signaling factors ; quality -of-life measures ; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care . A prospect i ve , cohort , closed-label study received approval from the Human Subjects Committee . Recruitment from outpatient clinics at an academic medical center and the community at large result ed in three hundred women giving signed consent . Seventy-five women who met strict inclusion /exclusion criteria were enrolled .  Baseline hormone evaluation was performed along with baseline experimental measures . Following this , women received compounded transdermal bioidentical hormone therapy of BiEst ( 80%Estriol/20%Estradiol ) , and /or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women . The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic , ischemic , or neuronal injury . Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of and rogens of DHEA and Testosterone if indicated . Experimental subjects were monitored for 36 months . Baseline , 2-month , and annual values were obtained for : blood pressure , body mass index , fasting glucose , Homeostasis Metabolic Assessment of Insulin Resistance ( HOMA-IR ) , fasting triglycerides , total Factor VII , Factor VIII , fibrinogen , Antithrombin III , Plasminogen Activator Inhibitor1(PAL-1 ) , C-reactive protein ( CRP ) , Interleukin-6 ( IL-6 ) , Matrix Metalloproteinase-9 ( MMP-9 ) , Tumor Necrosis Factor-alpha ( TNF ) , Insulin-like Growth Factor ( IGF-1 ) , and sex steroid levels . Psychosocial measures included : Greene Climacteric Scale , Visual Analog Pain Scale , Hamilton Anxiety Scale , Hamilton Depression Scale , Holmes Rahe Stress Scale , Job Strain , and Home Strain . Health outcome measures included the number of prescribed medications used , number of co-morbidities , and endometrial thickness in postmenopausal women with intact uteri . Subjects receiving  compounded transdermal bioidentical hormone therapy showed significant favorable changes in : Greene Climacteric Scale scores , Hamilton Anxiety Scale , Hamilton Depression Scale , Visual Analog Pain Scale , fasting glucose , fasting triglycerides , MMP-9 , C-reactive Protein , fibrinogen , Factor VII , Factor VIII , Insulin-Like Growth Factor 1 , and health outcomes of co-morbidities and a number of prescribed medications . Antithrombin III levels were significantly decreased at 36 months . All other measures did not exhibit significant effects . Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women . Cardiovascular biomarkers , inflammatory factors , immune signaling factors , and health outcomes were favorably impacted , despite very high life stress , and home and work strain in study subjects . The therapy did not adversely alter the net prothrombotic potential , and there were no associated adverse events . This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in population s with high perceived stress and a history of stressful life events prior to , or during the menopausal transition OBJECTIVES After recalling the classical contra-indication of hormone replacement therapy ( HRT ) concerning patients with a personal history of breast cancer ( BC ) , and arguments that may be opposed , the authors report the present results of a prospect i ve study undertaken in the Center of Breast Diseases in Saint-Louis hospital in Paris since February 1992 . PATIENTS AND METHODS By April 2001 , 230 patients had been included . A free interval of 2 years at least since the treatment of the primary BC has been observed . The reasons for prescribing HRT were vasomotor troubles ( flushes , nightly sweats ) or a dyspareunia , which were severe and not controlled by non-hormonal treatments . There was also an indication of a major osteoporotic or cardiovascular danger . In fact , many of these patients had a premature , artificial , chemo-induced menopause . The HRT most often used was an estro-progestin association ( estradiol + a progestin compound ) given either continuously or with a 5-d interruption each month . The mean duration of treatment was 2.5 years . RESULTS Results , concerning the improvement of menopause troubles , were remarkable in the great majority of troubles . HRT had to be stopped in 39 cases , reading as follows : 17 cases for relapses ( seven local , six in the contro-lateral breast and four metastases ( 7 % ) ) . Also , 22 patients ( 9 % ) interrupted their HRT for serious side-effects . A case-control study did not show any significant difference between with and without HRT patients concerning the overall survival without relapse . DISCUSSION AND CONCLUSIONS Quality of life of patients was often substantially improved , and a deleterious effect on the cancer disease was not found . Our results are in agreement with the literature from other countries . However , one must be cautious . In such circumstances , HRT must be prescribed with the informed consent of the patients and delivered in appropriate hospital and university centers . It is wished that large r and omised prospect i ve studies may be undertaken OBJECTIVES Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life ( QOL ) . The aims of this study were to measure menopausal symptoms , mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators . METHODS A prospect i ve , r and omized , placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms , anxiety and depressive symptoms , and QOL in 152 postmenopausal women over a 12 month study period .  Menopausal symptoms were measured using a modified Kupperman 's scale . Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life question naire , respectively . RESULTS Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high . Over 12 months , after adjustment for differences in baseline scoring , there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group . There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo . CONCLUSIONS These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood . In addition , the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians . Therefore , when considering the reasons for prescribing hormone replacement therapy in this population , protection against osteoporosis will for most women be the prime consideration The purpose of this study was to determine whether psychological support associated with  hormone replacement therapy ( HRT )  was more beneficial than replacement therapy alone . Our findings showed that HRT alone was more effective against vasomotor symptoms than HRT with psychological treatment ( PT ) . While the combination of both treatment modalities ( HRT + PT ) was more effective against insomnia , nervousness , melancholy , fatigue , palpitations , and vertigo .  Hormonal treatment alone and HRT with psychological treatment had little effect against paresthesia or tingling . Neither HRT alone nor HRT with psychological treatment was effective against joint and muscle pain or headache OBJECTIVE To investigate the effect of hormone treatment on  psychosocial distress of women during the menopausal transition ( aged 40 - 52 years , still menstruating and with minor symptoms ) , in a study carefully design ed to reduce bias and placebo effect . METHODS The study was r and omized , controlled by placebo , blinded to the subject , investigators and biostatistician , crossed-over after 6 months , and evaluated by a 77-item question naire every month for 12 months . The medication tested was continuous conjugated estrogens ( Premarin ) and cyclic medroxyprogesterone acetate ( Provera ) . RESULTS Of an eligible 105 apparently healthy women , recruited by advertisement , 83 completed the question naires for the study . R and omization was successful . While there was a substantial variation over time in the change of scores for all the psychosocial outcomes , there was no significant difference between active and placebo treatment when order of treatment allocation was ignored . However , a strong and consistent effect of the order of treatment allocation for many of the scores was found ; in particular , the effect of active treatment was substantially stronger when it was administered second . Positive effects of active treatment were found for the score for the overall symptom rating test ( p < 0.009 ) and its components of depression and feeling of inadequacy ( p = 0.011 ; p = 0.001 , respectively ) . CONCLUSIONS The use of hormones , given as a continuous estrogen and cyclic progestogen formulation after a formal calibration/run-in period , may have a beneficial effect on psychosocial distress experienced by women towards the end of their reproductive function Using a r and omized , placebo-controlled design , this study assessed the effects of estrogen alone ( ES ) or in combination with cyclic progesterone ( EP ) on daily ratings of mood and physical symptoms before and after 6 months of daily hormone treatment . Fifty-four postmenopausal women were recruited from the community at large and specifically selected as being asymptomatic at the time of enrollment and without significant psychiatric history . Ratings were obtained every day for 30 days prior to treatment and again every day during the last 30 days of treatment . Results revealed that when compared with pretreatment levels , women r and omized to EP ( n = 16 ) exhibited statistically significant increases in daily depression , cramping , and breast tenderness and a marginally significant increase in daily anxiety . However , these increases were mild , not clinical ly significant , and did not interfere with normal functioning . Women r and omized to ES ( n = 20 ) showed no significant change in daily mood measures , although they did experience an increase in breast tenderness with estrogen . A significant placebo ( n = 18 ) effect was observed , as there was a reliable reduction in daily irritability ratings ( p < 0.05 ) with placebo . These findings suggest that for most postmenopausal women , the use of hormones will not be associated with clinical ly significant changes in mood or physical symptoms , which weighs favorably into the cost-benefit ratio for women considering hormone replacement therapy Objective : The aim of this study was to examine changes in health-related quality of life ( HRQL ) during the menopausal transition , controlling for chronological aging , symptoms , and other covariates . Methods : This was a prospect i ve , longitudinal study of women aged 42 to 52 years at baseline recruited at seven US sites ( N = 3,302 ) in the multiethnic Study of Women 's Health Across the Nation . Women eligible for the cohort had an intact uterus , had at least one ovary , were not currently using exogenous hormones , were either premenopausal or early perimenopausal , and were self-identified as one of the study 's design ated racial/ethnic groups . Data from the baseline interview and six annual follow-up visits are reported . HRQL was assessed with five subscales from the Medical Outcomes Study Short-Form Health Survey , with reduced functioning defined as being in the lowest 25 % on a subscale . Covariates included symptoms , medical conditions , sociodemographics variables , physical activity , and psychological factors . Results : With adjustment for baseline age , chronological aging , and relevant covariates , the odds of reduced role-physical functioning were significantly greater at late perimenopause ( odds ratio , 1.46 ; 95 % CI , 1.08 - 1.99 ) and postmenopause ( odds ratio , 1.49 ; 95 % CI , 1.09 - 2.04 ) compared with premenopause . Menopause status was unrelated to bodily pain , vitality , role-emotional , or social functioning .  Hormone therapy users were more likely to report reduced functioning . Other variables significantly related to HRQL across all domains included vasomotor symptoms , urine leakage , poor sleep , arthritis , depressed mood , perceived stress , and stressful life events . Conclusions : The menopausal transition showed little impact on HRQL when adjusted for symptoms , medical conditions , and stress Background Menopausal hormone therapy ( MHT ) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women , and whether MHT affects mood in younger women . The ancillary Cognitive and Affective Study ( KEEPS-Cog ) of the Kronos Early Estrogen Prevention Study ( KEEPS ) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women . Methods and Findings KEEPS , a r and omized , double-blinded , placebo-controlled clinical trial , was conducted at nine US academic centers . Of the 727 women enrolled in KEEPS , 693 ( 95.3 % ) participated in the ancillary KEEPS-Cog , with 220 women r and omized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens ( o-CEE ) plus 200 mg/d micronized progesterone ( m-P ) for the first 12 d of each month , 211 women r and omized to receive 50 μg/d transdermal estradiol ( t-E2 ) plus 200 mg/d m-P for the first 12 d of each month , and 262 women r and omized to receive placebo pills and patches . Primary outcomes included the Modified Mini-Mental State examination ; four cognitive factors : verbal learning/memory , auditory attention/working memory , visual attention/executive function , and speeded language /mental flexibility ; and a mood measure , the Profile of Mood States ( POMS )  . MHT effects were analyzed using linear mixed-effects ( LME ) models , which make full use of all available data from each participant , including those with missing data . Data from those with and without full data were compared to assess for potential biases result ing from missing observations . For statistically significant results , we calculated effect sizes ( ESs ) to evaluate the magnitude of changes . On average , participants were 52.6 y old , and 1.4 y past their last menstrual period . By month 48 , 169 ( 24.4 % ) and 158 ( 22.8 % ) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment ( 3MS and cognitive factors ) and mood evaluations ( POMS ) , respectively . However , because LME models make full use all available data , including data from women with missing data , 95.5 % of participants were included in the final analysis ( n = 662 in cognitive analyses , and n = 661 in mood analyses ) . To be included in analyses , women must have provided baseline data , and data from at least one post-baseline visit . The mean length of follow-up was 2.85 y ( st and ard deviation [ SD ] = 0.49 ) for cognitive outcomes and 2.76 ( SD = 0.57 ) for mood outcomes . No treatment-related benefits were found on cognitive outcomes . For mood , model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment , compared to women on placebo . The model estimate for the depression subscale was −5.36 × 10−2 ( 95 % CI , −8.27 × 10−2 to −2.44 × 10−2 ; ES = 0.49 , p < 0.001 ) and for the anxiety subscale was −3.01 × 10−2 ( 95 % CI , −5.09 × 10−2 to −9.34 × 10−3 ; ES = 0.26 , p < 0.001 ) . Mood outcomes for women r and omized to t-E2 were similar to those for women on placebo . Importantly , the KEEPS-Cog results can not be extrapolated to treatment longer than 4 y. Conclusions The KEEPS-Cog findings suggest that for recently postmenopausal women , MHT did not alter cognition as hypothesized . However , beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE , but not with 4 y of t-E2 . The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles . Trial Registration Clinical Trials.gov NCT00154180 and OBJECTIVES We examined the efficacy of estrogen in the treatment of depression in perimenopausal women with and without hot flushes . STUDY DESIGN Women with perimenopause-related depression were r and omized in a double-blind parallel design to receive either 17beta-estradiol or placebo for 3 weeks . Subsequently , women receiving estradiol during the first 3 weeks continued receiving estradiol for an additional 3 weeks , whereas women who had received placebo crossed over to estradiol for 3 weeks . Outcome measures included st and ardized mood rating scales and a visual analog scale self-report instrument . RESULTS Of 34 female subjects , 16 received estradiol first and 18 received placebo first . After 3 weeks of estradiol , st and ardized mood rating scale scores and visual analog scale symptom scores ( eg , sadness , anhedonia , and social isolation ) were significantly decreased compared with baseline scores ( P < .01 ) and were significantly lower than scores in women receiving placebo ( P < .01 ) , who showed no significant improvement . Neither the presence of hot flushes nor the duration of treatment ( 3 weeks vs 6 weeks ) influenced outcome . A full or partial therapeutic response was seen in 80 % of subjects receiving estradiol and 22 % of those receiving placebo . CONCLUSION In this preliminary study estradiol replacement effectively treats perimenopausal depression independent of its salutary effects on vasomotor symptoms
This moderate to large effect size , showing lower ratings of depressed mood in treated patients compared with controls , implicated HRT as a potential treatment of or prophylactic for depression in menopausal women .
One can generalize from the studies review ed here only with great caution , but there is little evidence to support the use of estradiol to improve mood in nondepressed patients ( not surprisingly ) and some evidence to support the antidepressant efficacy of estradiol in perimenopausal but not postmenopausal women
BACKGROUND Controversy regarding the antidepressant efficacy of hormone replacement therapy ( HRT ) stems almost from its inception and reflects the same method ological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression .
Since this publication , multiple studies have aim ed to discern the relationship between HRT and menopausal mood .
METHODS The purpose of this systematic review is to examine the findings and quality of the evidence amassed since Zweifel and O'Brien 's meta- analysis .