Libido and orgasm in middle-aged woman

OBJECTIVES: Determine which social, demographic and sexual function variables that most influence libido or desire and orgasm domains in the premenopausal and postmenopausal women. METHODS: A cross-sectional analysis of 231 Colombian-born women, aged 40-62 years. The sexual function was measured by self-questionnaire. The analysis was performed by using the chi2-test and multivariate regression analysis. The sexual function was divided in five domains: desire, arousal, lubrication, orgasm, pain; additionally satisfaction was included. RESULTS: The women with a higher level of education and with a good perception of their satisfaction with their partners, reported better performance in the desire. Age and the non existence of sexual partner influenced in a negative way on the desire. In sexual active women the orgasm was negatively influenced by low satisfaction scores, lack of emotional closeness with their partners and low educational level. High scores in lubrication and desire were associated with a good performance in the orgasm. The hormone therapy (HT) was associated with better scores in orgasm. CONCLUSIONS: Age, level of education, the presence or lack of sexual partner, degree of satisfaction with emotional closeness with the partner and adequate lubrication, influence the desire and orgasm domains in a significant way. By identifying these associations we can then perform some inexpensive interventions. Improving lubrication for menopausal women. Including men in educational activities to sensitize them toward women's feelings. Organizing educational campaigns for middle-aged women to demystify that sexuality is only for young people.     

Cardiovascular and endocrine alterations after masturbation-induced orgasm in women.

OBJECTIVE: The present study investigated the cardiovascular, genital, and endocrine changes in women after masturbation-induced orgasm because the neuroendocrine response to sexual arousal in humans is equivocal. METHODS: Healthy women (N = 10) completed an experimental session, in which a documentary film was observed for 20 minutes, followed by a pornographic film for 20 minutes, and another documentary for an additional 20 minutes. Subjects also participated in a control session, in which participants watched a documentary film for 60 minutes. After subjects had watched the pornographic film for 10 minutes in the experimental session, they were asked to masturbate until orgasm. Cardiovascular (heart rate and blood pressure) and genital (vaginal pulse amplitude) parameters were monitored continuously throughout testing. Furthermore, blood was drawn continuously for analysis of plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone (LH), beta-endorphin, follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol. RESULTS: Orgasm induced elevations in cardiovascular parameters and levels of plasma adrenaline and noradrenaline. Plasma prolactin substantially increased after orgasm, remained elevated over the remainder of the session, and was still raised 60 minutes after sexual arousal. In addition, sexual arousal also produced small increases in plasma LH and testosterone concentrations. In contrast, plasma concentrations of cortisol, FSH, beta-endorphin, progesterone, and estradiol were unaffected by orgasm. CONCLUSIONS: Sexual arousal and orgasm produce a distinct pattern of neuroendocrine alterations in women, primarily inducing a long-lasting elevation in plasma prolactin concentrations. These results concur with those observed in men, suggesting that prolactin is an endocrine marker of sexual arousal and orgasm.     

A study of the psychological status and sexuality in middle-aged Bulgarian women: significance of the hormone replacement therapy (HRT)

OBJECTIVE: The psychoemotional and sexual status of Bulgarian urban postmenopausal women 10 years after the beginning of the period of extensive political, social, economic and cultural transitions was studied. SUBJECTS AND METHODS: Three hundred and thirty-two postmenopausal women (83.5% in natural menopause and 16.5% in surgical menopause) and 295 women with normal menstrual cycle in several Bulgarian cities and the capital were studied. A campaign for free-of-charge bone density measurement was announced and the examined subjects filled in an individual anonymous questionnaire. SPSS for Windows version 8.0 was used for the statistical processing of the results. The comparison was made between normally menstruating women (n=295), postmenopausal women on hormone replacement therapy (HRT) (n=36) and postmenopausal subjects without HRT (n=296). RESULTS: A significant correlation was observed between depression and sexual aversion, depression and pain with intercourse, depression and the change in the sexual life after menopause. The correlation between self-esteem and sexual thoughts, self-esteem and sexual desire, self-esteem and the arousal from the partner, self-esteem and orgasm also proved important. About 20% of the studied subjects reported depressive thoughts, 50% reported anxiety and the self-esteem was very low in 13%. These results can be explained in part with the economic stagnation in the country, the unemployment and uncertainty. However, 94% of Bulgarian women believe that they do well in life and rely on their professionalism and social positions. All parameters of sexual life are significantly lower in the postmenopausal group without HRT as compared both with menstruating women and postmenopausal women on HRT. Marital status influences them too. CONCLUSION: The change in the sexuality is related to the decline in the estrogen activity, the influence of the psychosocial factors, the lack of a permanent intimate partner, and the derogatory attitude of the society towards the sexuality of postmenopausal women.     

Are there gender differences in major depression and its response to antidepressants?

BACKGROUND: The prevalence of major depression for women is about twice that for men. This gender difference in prevalence rates has led to much research addressing gender differences in the presentation and features of major depression, and, to a lesser extent, research addressing gender differences in treatment response and personality. However, studies differ considerably in the population sampled, and findings vary significantly. In the current retrospective examination of data, we investigated all of these variables in one single sample of outpatients with major depression seen in a tertiary care centre. METHODS: A sample of 139 men and 246 women with major depression receiving antidepressant treatment (SSRIs, TCAs, SNRIs, MAOIs, or RIMAs) in an outpatient setting were contrasted with regard to symptoms and severity of depression, course of illness, treatment response, and personality. RESULTS: Women were found to experience more vegetative and atypical symptoms, anxiety, and anger than men, and to report higher severity of depression on self-report measures. Regarding personality, women scored higher on conscientiousness, the extraversion facet warmth, the openness facet feelings, and sociotropy. Effect sizes were small to moderate. No differences were found in the course of the illness and treatment response. LIMITATIONS: Findings are not generalizable to inpatient or community samples, and some of the gender differences may be accounted for by gender differences in treatment seeking behaviour. CONCLUSIONS: While men and women receiving antidepressant treatment show some gender differences in the psychopathology of major depression, these differences do not appear to translate into differences in response to antidepressants. Gender differences in personality appear less profound than in the average population, indicating the potential role of a certain personality type that predisposes individuals to develop clinical depression, independent of gender. CLINICAL RELEVANCE: The current examination underscores the role gender plays in the presentation and treatment of major depression.     

Burden of phase-specific sexual dysfunction with SSRIs

OBJECTIVE: This study examines phase-specific sexual dysfunction among patients who are being treated for major depression and who do not meet criteria for global sexual dysfunction. METHODS: 6297 adult outpatients receiving antidepressant monotherapy completed the Changes in Sexual Functioning Questionnaire (CSFQ). The sub-sample for this study (n = 3114) comprises participants who were receiving treatment with a SSRI or SNRI and did not meet the gender-specific criterion for global sexual dysfunction on the CSFQ. RESULTS: Among this sub-sample, 95.6% of women and 97.9% of men exhibited impairment in at least one phase of sexual functioning. Men were significantly more likely than women to experience dysfunction in the desire phase (91.2% vs. 79.0%; OR = 2.76; 95% C.I. = 2.14 to 3.5) and the orgasmic phase (85.1% vs. 45.4%; OR = 6.9; 95% C.I. = 5.6 to 8.4) but were significantly less likely than women to experience dysfunction in the arousal phase (71.9% vs. 83.3%; OR = .51; 95% C.I. = .43 to .62). The prevalence of phase-specific dysfunction did not vary significantly by SSRI/SNRI for males or females. CONCLUSION: Among patients who do not experience clinically significant global sexual dysfunction on SSRI/SNRI monotherapy, dysfunction in at least one phase of the sexual response cycle is very common and may reduce sexual health-related quality of life.     

Sexual function, menopause and hormone replacement therapy (HRT)

Objective: To assess the prevalence of female sexual dysfunction in premenopausal and postmenopausal women with and without hormone replacement therapy (HRT). To determine the relationship between menopause and sexual activity, and the impact of HRT on sexual function. Methods: A cross-sectional analysis of 231 Colombian-born women, aged 40–62 years. Sexual function was measured by self-questionnaire. The analysis was performed by using the χ²-test and multivariate regression analysis. The sexual function was divided in five domains: desire, arousal, lubrication, orgasm and pain; in addition, questioning about sexual satisfaction was included in the research. Results: In the study 38.1% of women showed sexual dysfunction in the desire, and 25% in the arousal, these two being the most affected domains. Even though menopause marginally decreases all stages of sexual function, this association was statistically significant only for the lubrication and pain domains. HRT improves sexual function in the orgasm, lubrication and pain domains in a statistically significant manner. The level of sexual satisfaction was better on postmenopausal women with HRT than ones without HRT. Age negatively influences almost all sexual function domains in a significant manner. Conclusions: Menopause affects in a negative manner some domains of female sexual function. HRT improves some factors of the sexual function during menopause but it not improves desire and arousal which were the most affected domains. There is a negative association between age and female sexual response in middle-aged women.     

Sexual dysfunction and cardiovascular diseases: a systematic review of prevalence

The aim of this study was to conduct a systematic review of the literature regarding the prevalence of sexual dysfunction in patients with cardiovascular diseases. An article search of the ISI Web of Science and PubMed databases using the search terms "sexual dysfunction”, “cardiovascular diseases”, “coronary artery disease", “myocardial infarct" and “prevalence” was performed.In total, 893 references were found. Non-English-language and repeated references were excluded. After an abstract analysis, 91 references were included for full-text reading, and 24 articles that evaluated sexual function using validated instruments were selected for this review. This research was conducted in October 2012, and no time restrictions were placed on any of the database searches. Reviews and theoretical articles were excluded; only clinical trials and epidemiological studies were selected for this review.The studies were mostly cross-sectional, observational and case-control in nature; other studies used prospective cohort or randomized clinical designs. In women, all domains of sexual function (desire, arousal, vaginal lubrication, orgasm, sexual dissatisfaction and pain) were affected. The domains prevalent in men included erectile dysfunction and premature ejaculation and orgasm.Sexual dysfunction was related to the severity of cardiovascular disease. When they resumed sexual activity, patients with heart disease reported significant difficulty, including a lack of interest in sex, sexual dissatisfaction and a decrease in the frequency of sexual activity.     

Frequency of sexual dysfunction in "normal" couples

In analyzing the responses of 100 predominantly white, well educated and happily married couples to a self-report questionnaire, this study examined the frequency of sexual problems experienced and the relations of those problems to sexual satisfaction. Although over 80 per cent of the couples reported that their marital and sexual relations were happy and satisfying, 40 per cent of the men reported erectile or ejaculatory dysfunction, and 63 per cent of the women reported arousal or orgasmic dysfunction. In addition, 50 per cent of the men and 77 per cent of the women reported difficulty that was not dysfunctional in nature (e.g., lack of interest or inability to relax). The number of "difficulties" reported was more strongly and consistently related to overall sexual dissatisfaction than the number of "dysfunctions."     

Sex differences in concordance rates between auditory event‐related potentials and subjective sexual arousal

Much research indicates men show a greater concordance between subjective and genital sexual arousal than do women. We investigated the relationship between subjective sexual arousal and brain activation in men and women. Subjective sexual arousal and auditory N1 and P3b ERP amplitudes were measured while 38 participants viewed erotic and non‐erotic films. Most notably, there was a significant correlation between N1 amplitude and sexual arousal in men; for women, there was a significant correlation between the P3b amplitude and sexual arousal. ERP amplitudes were inversely associated with reported arousal, suggesting that sexual arousal interferes with early tone processing for men, and with later tone processing for women. Lastly, for women, pornography/erotica consumption was negatively correlated with P3b amplitudes, suggesting that women who consume more pornography/erotica may also show greater attention to erotic films.     

The post-orgasmic prolactin increase following intercourse is greater than following masturbation and suggests greater satiety

Research indicates that prolactin increases following orgasm are involved in a feedback loop that serves to decrease arousal through inhibitory central dopaminergic and probably peripheral processes. The magnitude of post-orgasmic prolactin increase is thus a neurohormonal index of sexual satiety. Using data from three studies of men and women engaging in masturbation or penile-vaginal intercourse to orgasm in the laboratory, we report that for both sexes (adjusted for prolactin changes in a non-sexual control condition), the magnitude of prolactin increase following intercourse is 400% greater than that following masturbation. The results are interpreted as an indication of intercourse being more physiologically satisfying than masturbation, and discussed in light of prior research reporting greater physiological and psychological benefits associated with coitus than with any other sexual activities.     

Examining gender specificity of sexual response with concurrent thermography and plethysmography

Men's genital responses are significantly greater to sexual stimuli of their preferred gender compared to their nonpreferred gender (gender‐specific), whereas androphilic (i.e., sexually attracted to men) women's genital responses are similar to sexual stimuli depicting either women or men (gender‐nonspecific). This gendered pattern of genital response has only been demonstrated using vaginal photoplethysmography (VPP) in women and primarily penile plethysmography (PPG) in men. These measures assess different aspects of genital vasocongestion, thereby limiting comparisons between genders. Thermography is a newer sexual psychophysiology methodology that measures genital vasocongestion via temperature change and is better suited to assess sexual response between genders because the dependent measure, change in genital temperature, is similar for women and men. Further, previous studies have assessed gender specificity of sexual response across relatively short sexual stimuli, allowing only the examination of initial phases of sexual response. We examined gender specificity of sexual arousal by measuring women's and men's genital responses to lengthier stimuli with concurrent thermography and VPP/PPG. Gynephilic men (i.e., sexually attracted to women; n = 27) and androphilic women (n = 28) viewed 10‐min films depicting men masturbating, women masturbating, and a nonsexual film, and reported feelings of sexual arousal while genital responses were assessed. Across measures, men's sexual responses were gender‐specific and women's responses were gender‐nonspecific, indicating that the gender difference in gender specificity of arousal is robust to methodology and stimulus duration. These findings replicate previous research, extend knowledge of gendered sexual response, and highlight the utility of multimethod approaches in sexual psychophysiology.     

Is there an association between menopause status and sexual functioning?

OBJECTIVE: The purpose of this study was to address whether: (1) there is an association between menopause status and various aspects of sexual functioning, and (2) the relative contributions of menopause status and other variables to various aspects of sexual functioning. DESIGN: Analyses are based on 200 women from the Massachusetts Women's Health Study II, a population-based sample of women transitioning through the menopause who were not HRT users, who had not had a surgical menopause, and who had partners. The women were classified as pre-, peri-, or postmenopausal according to menstrual cycle characteristics. Estradiol, estrone, and follicle-stimulating hormone were also measured. Sexual functioning was measured in terms of satisfaction, desire, frequency of sexual intercourse, belief that interest declines with age, arousal compared with a younger age, difficulty reaching orgasm, and pain. Predictor variables included sociodemographics, health, vasomotor symptoms, psychological variables, partner variables, and lifestyle behaviors. RESULTS: Menopause status was significantly related to lower sexual desire, a belief that interest in sexual activity declines with age, and women's reports of decreased arousal compared with when in their 40s. Menopause status was unrelated to other aspects of sexual functioning in either unadjusted or multiple regression analyses. In analyses in which log estradiol (E2) was included in addition to menopause status, log E2 was only related to pain. In multiple regression analyses, other factors such as health, marital status (or new partner), mental health, and smoking had a greater impact on women's sexual functioning than menopause status. CONCLUSIONS: Menopause status, but not E2, is related to some, but not all, aspects of sexual functioning. This may be due to menopause per se or other factors associated with menopause and aging (e.g., increased sexual dysfunction among aging men). Menopause status has a smaller impact on sexual functioning than health or other factors.     

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.     

Sexual satisfaction among middle-aged couples: correlation with frequency of intercourse and health status

The central hypothesis of this investigation is that the greater the sexual satisfaction that a couple reports from their sexual relationship, the better will be their adjustment to the changes that occur during middle age, as reflected in their reported health status and health behaviour. Forty-seven married couples, of North African Jewish origin, were investigated, the women being in the age range 48-53 yr. The findings regarding reported frequency of sexual intercourse and sexual satisfaction of women and men separately showed that a great majority of both men (87%) and women (74%) reported a decrease in sexual activity over the 5 yr preceding the study. Most of the men (56%) said the change was due to the aging process, whereas the women's responses were more varied and included aging, worries and decrease in sexual interest or desire. Eighty percent of the men reported satisfaction in their sexual relationship with their wives, but only 43% of the women stated that they were satisfied. A significant correlation was found, for women only, between the degree of satisfaction and the change in frequency of intercourse. Among the women there was also a positive correlation between general life satisfaction and sexual satisfaction. The hypothesis in regard to mutual (couple) sexual satisfaction was not confirmed in the men. It was validated in the women in regard to only two of the four criteria used - their perception of their health status and of their well-being. The women perceived the sexual satisfaction of their husbands much more accurately than the husbands perceived that of their wives.     

Male bisexual arousal: A matter of curiosity?

Conflicting evidence exists regarding whether bisexual-identified men are sexually aroused to both men and women. We hypothesized that a distinct characteristic, level of curiosity about sexually diverse acts, distinguishes bisexual-identified men with and without bisexual arousal. Study 1 assessed men's (n = 277) sexual arousal via pupil dilation to male and female sexual stimuli. Bisexual men were, on average, higher in their sexual curiosity than other men. Despite this general difference, only bisexual-identified men with elevated sexual curiosity showed bisexual arousal. Those lower in curiosity had responses resembling those of homosexual men. Study 2 assessed men's (n = 72) sexual arousal via genital responses and replicated findings of Study 1. Study 3 provided information on the validity on our measure of sexual curiosity by relating it to general curiosity and sexual sensation seeking (n = 83). Based on their sexual arousal and personality, at least two groups of men identify as bisexual.     

Sexuality in Brazilian women aged 40 to 65 years with 11 years or more of formal education: associated factors

OBJECTIVE: To evaluate factors associated with the sexuality of middle-aged women. DESIGN: Cross-sectional, population-based survey using an anonymous self-response questionnaire. A total of 276 Brazilian-born women, 40 to 65 years old with at least 11 years of formal education, participated in the study. The evaluation instrument was based on the Short Personal Experiences Questionnaire. Seven components were analyzed: satisfaction in sexual activities, orgasm, intensity of desire, self-classification of sexual life, frequency of arousal, sexual activity, and sexual fantasies. Sociodemographic, clinical, behavioral, and reproductive factors were evaluated. Data were analyzed using the chi and Fisher exact tests and Poisson multiple regression analysis. Prevalence ratios (PRs) and their 95% CIs were calculated. RESULTS: The median sexuality score was 9 (range, 2.45-13.77). Bivariate analysis indicated that being 50 years of age or older; in the menopausal transition or postmenopause; not having a sexual partner; reporting hot flushes, insomnia, depression, nervousness, sedentary lifestyle, arterial hypertension, or urinary incontinence; and poor self-perception of health were significantly associated with a below median sexuality score. Multiple regression analysis showed that the prevalence of below median scores was higher in older women (prevalence ratio [PR] = 1.03, 95% CI: 1.01-1.05) and in those with insomnia (PR = 1.46, 95% CI: 1.08-1.96). Having a sexual partner (PR = 0.68, 95% CI: 0.50-0.92) and feeling well (PR = 0.73, 95% CI: 0.57-0.94) was associated with a protective effect against a below median sexuality score. CONCLUSIONS: Older women and those with insomnia were more likely to have a low sexuality score, whereas those with a sexual partner and who felt well were less likely to have a low sexuality score.     

Free T4 index and clinical outcome in patients with depression

INTRODUCTION: Many studies of patients with major depression have reported that a significant decrease in serum free T(4) index is associated with specific treatments; what has been unanswered is whether these observations are generalizable. This study evaluated baseline thyroid function and its relationship to rapidity of treatment response as measured by hospital length of stay (HLOS). METHODS: Admission thyroid indices and HLOS data were harvested from the medical record of patients hospitalized for depression, both unipolar and bipolar. The relationship between admission thyroid indices and HLOS was evaluated using survival models. RESULTS: Controlling for age and year of discharge, an inverse relationship between FT(4) index (FT(4)I) and HLOS was present in men, but not in women. The mean HLOS stratified by gender and median FT(4)I was 50% shorter in men with a relatively high FT(4)I in comparison to the other three groups. LIMITATIONS: This is a retrospective study limited by the absence of a structured diagnostic psychiatric interview and prospective controlled antidepressant evaluation. CONCLUSION: These data would suggest that a relatively elevated FT(4) index in depressed men is associated with a faster antidepressant response time. Prospective study is encouraged to further clarify this potential thyroid/gender relationship and whether thyroid supplementation can accelerate the improvement in depression as measured by HLOS.     

Effects of antidepressant treatments on polymorphonuclear elastase levels in patients with depression

BACKGROUND: We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. METHODS: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). RESULTS: There was a positive correlation between Delta PMNE levels and Delta HDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. CONCLUSION: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. CLINICAL IMPLICATION AND LIMITATIONS: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression.     

Polysomnography and criteria for the antidepressant response to sleep deprivation

BACKGROUND: One night of total or partial sleep deprivation (SD) produces a temporary remission in 40-60% of patients with major depression. Yet no attempts to determine the optimum response criterion(a) for the antidepressant response to SD have been published. METHODS: Twenty-three unmedicated major depression patients received polysomnography (PSG) on an adaptation night; a baseline night; a partial SD (PSD) night (awake after 3 a.m.); and a "recovery" night. Subjects received the Hamilton Depression Rating Scale (HDRS17) at standard times during baseline and PSD days and at 8 a.m. after the "recovery" night. Response was defined as percent decrease in the modified HDRS17 (HDRS17Mod) (omitting sleep and weight loss items) from baseline to the minimum following PSD. Using cutoffs of 30%, 35%, 40%, and 50% to dichotomize responders and nonresponders, PSG variables were analyzed for between-group differences. RESULTS: All cutoffs differentiated responders' and nonresponders' mood response to PSD despite similar baseline values. Sleep continuity measures most consistently differed between responders and nonresponders on baseline and recovery nights. None of the response cutoffs tested were clearly "best" in terms of detecting the most PSG differences between groups. LIMITATIONS: More subjects may be needed. CONCLUSIONS: Given the increasing interest in SD for clinical and research applications, as well as its proposed use for subtyping depression, further study to determine the optimal response criterion(a) for the antidepressant response to SD is warranted. Planned pooling of multisite data on standardized SD protocols could help determine the optimal cutpoint for response.     

Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial

BACKGROUND: A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine. METHODS: 127 patients were randomly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out. RESULTS: Patients receiving folate showed a significant increase in plasma folate.This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men. Overall there was a significantly greater improvement in the fluoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (P<0.001).A percentage of 93. 9 of women, who received the folic acid supplement, showed a good response (>50% reduction in score) as compared to 61.1% of women who received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients reported such symptoms (P<0.05). LIMITATIONS AND CONCLUSIONS: Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.