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The Cochrane Database of Systematic... Apr 2015Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective.
OBJECTIVES
To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism.
DATA COLLECTION AND ANALYSIS
Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses.
MAIN RESULTS
We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs.
AUTHORS' CONCLUSIONS
Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.
Topics: 5-alpha Reductase Inhibitors; Adult; Androgen Antagonists; Body Mass Index; Contraceptive Agents, Female; Cyproterone Acetate; Desogestrel; Drug Combinations; Eflornithine; Ethinyl Estradiol; Female; Finasteride; Flutamide; Hirsutism; Humans; Hypoglycemic Agents; Metformin; Quality of Life; Randomized Controlled Trials as Topic; Spironolactone
PubMed: 25918921
DOI: 10.1002/14651858.CD010334.pub2 -
The Cochrane Database of Systematic... Jan 2015During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of various perimenopausal and postmenopausal symptoms (for example hot flushes, night sweats, vaginal dryness). Dehydroepiandrosterone (DHEA) is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens. It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function (for example libido, dyspareunia, satisfaction). Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety. This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials.
OBJECTIVES
To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase.
SEARCH METHODS
The databases that we searched (3 June 2014) with no language restrictions applied were the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the trials registers. Reference lists of retrieved articles were checked.
SELECTION CRITERIA
We included randomised controlled trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment for a minimal treatment duration of seven days in peri- and postmenopausal women.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data after assessing eligibility for inclusion and quality of studies. Authors were contacted for additional information.
MAIN RESULTS
Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo.There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison.There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%).
AUTHORS' CONCLUSIONS
There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo.
Topics: Acne Vulgaris; Dehydroepiandrosterone; Dyspareunia; Estrogens; Female; Hot Flashes; Humans; Perimenopause; Postmenopause; Quality of Life; Randomized Controlled Trials as Topic; Selection Bias; Sweating
PubMed: 25879093
DOI: 10.1002/14651858.CD011066.pub2 -
BMJ Case Reports Mar 2015Pituitary gland metastasis from primary tumours is uncommon on its own. Rarely, some of these primary tumours may be of unknown origin. This metastasis to the pituitary... (Review)
Review
Pituitary gland metastasis from primary tumours is uncommon on its own. Rarely, some of these primary tumours may be of unknown origin. This metastasis to the pituitary gland could manifest as diabetes insipidus, cranial nerve palsies, headaches, fatigue and other symptoms. In rare cases, it could present as loss of libido. We describe here this rare presentation, loss of libido, examine the diagnosis and management undertaken, and provide a systematic review of the literature for similar cases.
Topics: Adenocarcinoma; Adult; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Hydrocortisone; Libido; Male; Pituitary Neoplasms; Thyroxine
PubMed: 25827917
DOI: 10.1136/bcr-2014-208735 -
The Cochrane Database of Systematic... Feb 2015Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence... (Review)
Review
BACKGROUND
Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence levels and it is accepted that there is a high proportion of hidden sexual victimisation. Surveys report high levels of psychiatric morbidity in survivors of sexual offences.Biological treatments of sex offenders include antilibidinal medication, comprising hormonal drugs that have a testosterone-suppressing effect, and non-hormonal drugs that affect libido through other mechanisms. The three main classes of testosterone-suppressing drugs in current use are progestogens, antiandrogens, and gonadotropin-releasing hormone (GnRH) analogues. Medications that affect libido through other means include antipsychotics and serotonergic antidepressants (SSRIs).
OBJECTIVES
To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or are at risk of sexual offending.
SEARCH METHODS
We searched CENTRAL (2014, Issue 7), Ovid MEDLINE, EMBASE, and 15 other databases in July 2014. We also searched two trials registers and requested details of unidentified, unpublished, or ongoing studies from investigators and other experts.
SELECTION CRITERIA
Prospective controlled trials of antilibidinal medications taken by individuals for the purpose of preventing sexual offences, where the comparator group received a placebo, no treatment, or 'standard care', including psychological treatment.
DATA COLLECTION AND ANALYSIS
Pairs of authors, working independently, selected studies, extracted data, and assessed the risk of bias of included studies. We contacted study authors for additional information, including details of methods and outcome data.
MAIN RESULTS
We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis).Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation.Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect.
PRIMARY OUTCOME
recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated.Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone.
SECONDARY OUTCOMES
The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes.
AUTHORS' CONCLUSIONS
We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending.The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained.It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.
Topics: Adolescent; Adult; Aged; Androgen Antagonists; Antipsychotic Agents; Child; Child Abuse, Sexual; Desensitization, Psychologic; Exhibitionism; Humans; Libido; Male; Middle Aged; Randomized Controlled Trials as Topic; Rape; Recurrence; Sex Offenses; Sexual Behavior
PubMed: 25692326
DOI: 10.1002/14651858.CD007989.pub2 -
The Journal of Clinical Endocrinology... Oct 2014Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and... (Meta-Analysis)
Meta-Analysis Review
Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis.
CONTEXT
Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms.
OBJECTIVE
We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function.
METHODS
We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I(2) statistic.
RESULTS
We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, -0.02 to 0.73; P value = .06; I(2) = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs.
CONCLUSIONS
Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.
Topics: Adjuvants, Immunologic; Adrenal Glands; Aging; Dehydroepiandrosterone; Female; Humans; Middle Aged; Postmenopause; Randomized Controlled Trials as Topic; Sexuality
PubMed: 25279571
DOI: 10.1210/jc.2014-2261 -
Asian Journal of Andrology Sep 2013This meta-analysis was performed to assess sexual functions following adult male circumcision. We searched the Cochrane Central Register of Controlled Trials, PUBMED,... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis was performed to assess sexual functions following adult male circumcision. We searched the Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2013 to identify all eligible studies that reported on men's sexual function after circumcision. The Cochrane Collaboration's RevMan 5.2 software was employed for data analysis, and the fixed or the random effect model was selected depending on the proportion of heterogeneity. We identified 10 studies, which described a total of 9317 circumcised and 9423 uncircumcised men who were evaluated for the association of circumcision with male sexual function. There were no significant differences in sexual desire (odds ratio (OR): 0.99; 95% confidence interval (CI): 0.92-1.06), dyspareunia (OR: 1.12; 95% CI: 0.52-2.44), premature ejaculation (OR: 1.13; 95% CI: 0.83-1.54), ejaculation latency time (OR: 1.33; 95% CI: 0.69-1.97), erectile dysfunctions (OR: 0.90; 95% CI: 0.65-1.25) and orgasm difficulties (OR: 0.97; 95% CI: 0.83-1.13). These findings suggest that circumcision is unlikely to adversely affect male sexual functions. However, these results should be evaluated in light of the low quality of the existing evidence and the significant heterogeneity across the various studies. Well-designed and prospective studies are required for a further understanding of this topic.
Topics: Adolescent; Adult; Case-Control Studies; Circumcision, Male; Coitus; Cross-Sectional Studies; Dyspareunia; Ejaculation; Erectile Dysfunction; Humans; Libido; Male; Middle Aged; Premature Ejaculation
PubMed: 23749001
DOI: 10.1038/aja.2013.47 -
The Cochrane Database of Systematic... Jun 2013Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
SEARCH METHODS
Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
SELECTION CRITERIA
Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
MAIN RESULTS
Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
AUTHORS' CONCLUSIONS
SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.
Topics: Adolescent; Adult; Female; Humans; Luteal Phase; Middle Aged; Premenstrual Syndrome; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 23744611
DOI: 10.1002/14651858.CD001396.pub3 -
The Cochrane Database of Systematic... Nov 2012Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation, sexual arousal, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation, sexual arousal, or overall sexual satisfaction. These are major aspects of tolerability and can highly affect patients' compliance.
OBJECTIVES
To determine the effects of different strategies (e.g. dose reduction, drug holidays, adjunctive medication, switching to another drug) for treatment of sexual dysfunction due to antipsychotic therapy.
SEARCH METHODS
An updated search was performed in the Cochrane Schizophrenia Group's Trials Register (3 May 2012) and the references of all identified studies for further trials.
SELECTION CRITERIA
We included all relevant randomised controlled trials involving people with schizophrenia and sexual dysfunction.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated random effects risk ratios (RR) with 95% confidence intervals (CI), for crossover trials we calculated Odds Ratios (OR) with 95% CI. For continuous data, we calculated mean differences (MD) on the basis of a random-effects model. We analysed cross-over trials under consideration of correlation of paired measures.
MAIN RESULTS
Currently this review includes four pioneering studies (total n = 138 , duration two weeks to four months), two of which are cross-over trials. One trial reported significantly more erections sufficient for penetration when receiving sildenafil compared with when receiving placebo (n = 32, MD 3.20 95% CI 1.83 to 4.57), a greater mean duration of erections (n = 32, MD 1.18 95% CI 0.52 to 1.84) and frequency of satisfactory intercourse (n = 32, MD 2.84 95% CI 1.61 to 4.07). The second trial found no evidence for selegiline as symptomatic treatment for antipsychotic-induced sexual dysfunction compared with placebo (n = 10, MD change on Aizenberg's sexual functioning scale -0.40 95% CI -3.95 to 3.15). No evidence was found for switching to quetiapine from risperidone to improve sexual functioning (n = 36, MD -2.02 95% CI -5.79 to 1.75). One trial reported significant improvement in sexual functioning when participants switched from risperidone or an typical antipsychotic to olanzapine (n = 54, MD -0.80 95% CI -1.55 to -0.05).
AUTHORS' CONCLUSIONS
We are not confident that cross-over studies are appropriate for this participant group as they are best for conditions that are stable and for interventions with no physiological and psychological carry-over. Sildenafil may be a useful option in the treatment of antipsychotic-induced sexual dysfunction in men with schizophrenia, but this conclusion is based only on one small short trial. Switching to olanzapine may improve sexual functioning in men and women, but the trial assessing this was a small, open label trial. Further well designed randomised control trials that are blinded and well conducted and reported, which investigate the effects of dose reduction, drug holidays, symptomatic therapy and switching antipsychotic on sexual function in people with antipsychotic-induced sexual dysfunction are urgently needed.
Topics: Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Drug Substitution; Erectile Dysfunction; Female; Humans; Male; Olanzapine; Piperazines; Purines; Randomized Controlled Trials as Topic; Selegiline; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Vasodilator Agents
PubMed: 23152218
DOI: 10.1002/14651858.CD003546.pub3 -
The Cochrane Database of Systematic... Oct 2010Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH.
OBJECTIVES
To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS).
SEARCH STRATEGY
We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines.
SELECTION CRITERIA
Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months.
DATA COLLECTION AND ANALYSIS
JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term).
MAIN RESULTS
Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia, versus finasteride. Versus tamsulosin, peak urine flow and QoL improved equally well versus finasteride. However, finasteride was associated with a lower risk of surgical intervention compared to doxazosin, but not to terazosin, while finasteride and doxazosin were no different for risk of acute urinary retention. Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin. Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well (≥ 4 point improvement).For finasteride, there was an increased risk of ejaculation disorder, impotence, and lowered libido, versus placebo. Versus doxazosin, finasteride had a lower risk of asthenia, dizziness, and postural hypotension, and versus terazosin, finasteride had a significant, lower risk of asthenia, dizziness, and postural hypotension.
AUTHORS' CONCLUSIONS
Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.
Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Disease Progression; Doxazosin; Drug Therapy, Combination; Enzyme Inhibitors; Finasteride; Humans; Male; Prostatic Hyperplasia; Prostatism; Randomized Controlled Trials as Topic
PubMed: 20927745
DOI: 10.1002/14651858.CD006015.pub3 -
Endocrine Reviews Feb 2010Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid... (Review)
Review
Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.
Topics: Analgesics, Opioid; Animals; Endocrine System; Endocrine System Diseases; Female; Humans; Hypogonadism; Male; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 19903933
DOI: 10.1210/er.2009-0009