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The Journal of Urology Oct 2019With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility....
PURPOSE
With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility. We reviewed the literature regarding the effects of cannabis on male fertility.
MATERIALS AND METHODS
We performed a literature search using PubMed®/MEDLINE® to identify relevant studies of the effects of cannabis on male fertility. Relevant studies were identified and reviewed.
RESULTS
The strongest evidence of cannabis induced alterations in male fertility is in the category of semen parameters. Research supports a role for cannabis in reducing sperm count and concentration, inducing abnormalities in sperm morphology, reducing sperm motility and viability, and inhibiting capacitation and fertilizing capacity. Animal models demonstrate a role for cannabis in testicular atrophy, and reduced libido and sexual function but to our knowledge these results have not yet been replicated in human studies. Studies of hormonal changes suggest inconclusive effects on testosterone levels, lowered luteinizing hormone levels and unchanged follicle-stimulating hormone levels.
CONCLUSIONS
Current research suggests that cannabis may negatively impact male fertility. Further studies are needed to validate that robust findings in animal models will carry over into human experience. Clinicians should be aware of these potential effects when prescribing medical marijuana therapies to men of reproductive age, and they should consider the degree of cannabis use as a possible component of a complete male infertility workup.
Topics: Animals; Cell Survival; Disease Models, Animal; Fertility; Humans; Infertility, Male; Male; Medical Marijuana; Semen; Sperm Motility; Testis
PubMed: 30916627
DOI: 10.1097/JU.0000000000000248 -
The Journal of Clinical and Aesthetic... Jul 2016Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In... (Review)
Review
Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.
PubMed: 27672412
DOI: No ID Found -
Acta Dermato-venereologica Jan 2019Treatment of male androgenetic alopecia with 5α-reductase inhibitors is efficacious. However, the risk of adverse sexual effects remains controversial. This systematic... (Meta-Analysis)
Meta-Analysis
Treatment of male androgenetic alopecia with 5α-reductase inhibitors is efficacious. However, the risk of adverse sexual effects remains controversial. This systematic review and meta-analysis investigated the risk of adverse sexual effects due to treatment of androgenetic alopecia in male patients with finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double-blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of 5α-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction (95% confidence interval (95% CI) 1.19-2.08). The relative risk was 1.66 (95% CI 1.20-2.30) for finasteride and 1.37 (95% CI 0.81-2.32) for dutasteride. Both drugs were associated with an increased risk, although the increase was not statistically significant for dutasteride. As studies into dutasteride were limited, further trials are required. It is important that physicians are aware of, and assess, the possibility of sexual dysfunction in patients treated with 5α-reductase inhibitors.
Topics: 5-alpha Reductase Inhibitors; Administration, Oral; Alopecia; Dutasteride; Ejaculation; Erectile Dysfunction; Finasteride; Humans; Libido; Male; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sexual Behavior; Sexual Dysfunction, Physiological
PubMed: 30206635
DOI: 10.2340/00015555-3035 -
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 -
Clinical Interventions in Aging 2019We performed a meta-analysis to evaluate the efficacy and safety of dutasteride and finasteride in treating men with androgenetic alopecia (AGA) during a 24-week...
AIM
We performed a meta-analysis to evaluate the efficacy and safety of dutasteride and finasteride in treating men with androgenetic alopecia (AGA) during a 24-week treatment cycle.
METHODS
Randomized controlled trials of dutasteride and finasteride for treating AGA were searched using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The data were calculated using Rev Man v5.3.0. The reference lists of retrieved studies were also investigated.
RESULTS
Three articles including 576 participants which compared dutasteride with finasteride were selected for our analysis. The mean change in total hair count (mean difference [MD], 28.57; 95% CI, 18.75-38.39; <0.00001), investigator's assessment of global photographs for the vertex (MD, 0.68; 95% CI, 0.13-1.23; =0.02) and frontal (MD, 0.63; 95% CI, 0.13-1.13; =0.01) views, panel global photographic assessment for the vertex (MD, 0.17; 95% CI, 0.09-0.24; <0.00001) and frontal (MD, 0.25; 95% CI, 0.18-0.31; <0.00001) views, and subjects' assessment (MD, 0.56; 95% CI, 0.18-0.94; =0.003) suggested that dutasteride provided a better efficacy in treating men with AGA compared with finasteride. With regard to the assessment of safety, altered libido (=0.54), erectile dysfunction (=0.07), and ejaculation disorders (=0.58), dutasteride did not show a significant difference compared with finasteride.
CONCLUSION
Dutasteride seems to provide a better efficacy compared with finasteride in treating AGA. The two drugs appear to show similar rates of adverse reactions, especially in sexual dysfunction.
Topics: 5-alpha Reductase Inhibitors; Adult; Alopecia; Dutasteride; Finasteride; Humans; Male; Middle Aged; Safety; Treatment Outcome; Young Adult
PubMed: 30863034
DOI: 10.2147/CIA.S192435 -
Journal of Human Reproductive Sciences 2023Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive...
BACKGROUND
Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men.
OBJECTIVE
The objective of this study was to assess and systematically review the effects of AAS on male fertility parameters, spermiogram, testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) and to review reversibility and other morbidity impacting fertility.
METHODS
Eligibility criteria - We included studies mentioning data about adult males using supraphysiologic doses of AAS for sports performance or appearance enhancement, with comparison data from general population or matched controls if available reporting fertility parameters and sexual performance. Information sources - A systematic literature search was performed using PubMed, MEDLINE, EMBASE, Google Scholar and World of Science. Controlled clinical trials randomised or nonrandomised (if available), case series with or without matched controls, case reports, cross-sectional surveys, reports on follow-up of subjects caught in doping test and their fertility parameters when reported. Risk of bias/quality assessment - The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.
RESULTS
Included studies - Thirty-two studies were included. There were 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports. The study population comprised 9371 individuals, of which 2671 were AAS users. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population. These levels remained low for 3-6 months after stopping AAS. One year after stopping AAS, the users and naïve population had insignificant differences in FSH and LH values. The total testosterone (TT) levels were comparable in users and naïve populations at baseline, 3 months and 6 months after stopping, but at 1 year, TT values were lower in AAS users. Sperm concentration in AAS users and naïve population was similar, but sperm motility was lower in AAS users. The testicular size was lower in AAS users. The erectile function improved with AAS use, but on withdrawal, there was decreased libido and erectile dysfunction. Most AAS users need additional medications to mitigate detrimental effects on fertility. Description of the effect - AAS use negatively impacted the gonadotrophin levels and had lower sperm motility and testicular size. Strength - Comprehensive review of 32 publications, study population of 9371 individuals, of which 2671 were AAS users, meta-analysis of reproductive hormones, semen parameters and testis size.
LIMITATIONS
The limitations are small sample size of most of the studies, polypharmacy, lack of information on dosing and high heterogeneity.
INTERPRETATION
AAS use is detrimental for sperm motility and has a partially reversible negative impact on male fertility. Users must be cautioned about its negative impact on libido and erectile function. PROSPERO Registration No. CRD42023411294.
PubMed: 38322636
DOI: 10.4103/jhrs.jhrs_90_23 -
American Journal of Men's Health Mar 2018Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with... (Meta-Analysis)
Meta-Analysis Review
Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Depression; Humans; Male; Sexual Dysfunctions, Psychological
PubMed: 29019272
DOI: 10.1177/1557988317734519 -
Best Practice & Research. Clinical... Sep 2022Anabolic-androgenic steroid (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to... (Review)
Review
Anabolic-androgenic steroid (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to stop AAS are prone to distressing withdrawal symptoms which may trigger relapse in use. It is important to develop therapies to support AAS withdrawal. The illicit nature of AAS use has impeded the robust characterisation of its clinical withdrawal syndrome within any single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use, and AAS withdrawal. Reported clinical features of AAS withdrawal include headache, fatigue, myalgia, restlessness, insomnia, low mood and libido, anorexia, suicidal ideation, body image dissatisfaction, and steroid cravings; novel therapies for AAS withdrawal would need evaluation against these symptoms.
Topics: Anabolic Agents; Androgens; Humans; Male; Performance-Enhancing Substances; Steroids; Testosterone Congeners
PubMed: 35999138
DOI: 10.1016/j.beem.2022.101691 -
BMJ Open Nov 2017To assess the relative effects of individual testosterone products among hypogonadal men. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the relative effects of individual testosterone products among hypogonadal men.
DESIGN
Systematic review and network meta-analysis.
METHODS
We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane's risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS).
RESULTS
Eighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) -0.26, 95% CI -0.41 to -0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD -0.23, 95% CI -0.44 to -0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs.
CONCLUSION
Despite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm.
PROSPERO REGISTRATION NUMBER
CRD42014009963.
Topics: Androgens; Humans; Hypogonadism; Male; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Testosterone
PubMed: 29150464
DOI: 10.1136/bmjopen-2016-015284 -
Toxicology and Applied Pharmacology Nov 2023Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The...
Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.
Topics: Adult; Male; Humans; Animals; Mice; Minoxidil; Finasteride; Alopecia; Administration, Oral; Prostatic Hyperplasia; Treatment Outcome
PubMed: 37805090
DOI: 10.1016/j.taap.2023.116710