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Fulltext Clinical factors associated with sexual dysfunction among men in methadone maintenance treatment and buprenorphine maintenance treatment: a meta-analysis study

Yee A, Loh HS, Hisham Hashim HM, Ng CG

Int J Impot Res, 2014 Sep-Oct;26(5):161-6.
PMID: 24990199 DOI: 10.1038/ijir.2014.18

Methadone maintenance treatment is proven to be effective treatment for opioid dependence. Of the many adverse events reported, sexual dysfunction is one of the most common side effects. However, there may be other clinical factors that are associated with sexual dysfunction among methadone users. We conducted a meta-analysis to examine the clinical factors associated with sexual dysfunction among male patients on methadone and buprenorphine treatments, of which eligible studies were selected using prior defined criteria. A total of 2619 participants from 16 eligible studies, published from inception till December 2012, were identified from the PubMed, OVID and EMBASE databases. The included studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval (CI), 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (odds ratio=4.01, 95% CI, 1.52-10.55, P=0.0049). Our study shows that eight clinical factors are associated with sexual dysfunction among men receiving opioid substitution treatment, namely age, hormone assays, duration of treatment, methadone dose, medical status, psychiatric illness, other current substance use and familial status, and methadone versus buprenorphine treatment. Despite the methodological limitations, the findings of this meta-analysis study may offer better insights to clinicians in dealing with both sexual dysfunction and its related problems.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced*
Serotonin Selective Reuptake Inhibitors (SSRIs) and Female Sexual Dysfunction (FSD): Hypothesis on its Association and Options of Treatment

Rappek NAM, Sidi H, Kumar J, Kamarazaman S, Das S, Masiran R, et al.

Curr Drug Targets, 2018;19(12):1352-1358.
PMID: 28025939 DOI: 10.2174/1389450117666161227142947

Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced*
The prevalence of sexual dysfunction among male patients on methadone and buprenorphine treatments: a meta-analysis study

Yee A, Loh HS, Hisham Hashim HM, Ng CG

J Sex Med, 2014 Jan;11(1):22-32.
PMID: 24344738 DOI: 10.1111/jsm.12352

INTRODUCTION: For many years, methadone has been recognized as an effective maintenance treatment for opioid dependence. However, of the many adverse events reported, sexual dysfunction is one of the most common side effects.
AIM: We conducted a meta-analysis to evaluate the prevalence of sexual dysfunction among male patients on methadone and buprenorphine treatments.
METHODS: Relevant studies published from inception until December 2012 were identified by searching PubMed, OVID, and Embase. Studies were selected using prior defined criteria. Heterogeneity, publication bias, and odds ratio were assessed thoroughly.
MAIN OUTCOME MEASURES: To examine the prevalence and odds ratio of sexual dysfunctions among the methadone and buprenorphine groups.
RESULTS: A total of 1,570 participants from 16 eligible studies were identified in this meta-analysis. The studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval [CI], 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (OR = 4.01, 95% CI, 1.52-10.55, P = 0.0049).
CONCLUSIONS: Evidence showed that the prevalence of sexual dysfunction was higher among the users of methadone compared with buprenorphine. Patients with sexual difficulty while on methadone treatment were advised to switch to buprenorphine.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced
Female sexual dysfunction in patients treated with antidepressant-comparison between escitalopram and fluoxetine

Sidi H, Asmidar D, Hod R, Guan NC

J Sex Med, 2012 May;9(5):1392-9.
PMID: 21477024 DOI: 10.1111/j.1743-6109.2011.02256.x

Selective serotonin reuptake inhibitor is one of the most widely used antidepressant and commonly associated with female sexual dysfunction (FSD).

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced*
Association of brain-derived neurotrophic factor valine to methionine polymorphism with sexual dysfunction following selective serotonin reuptake inhibitor treatment in female patients with major depressive disorder

Nazree NE, Mohamed Z, Reynolds GP, Mohd Zain S, Masiran R, Sidi H, et al.

Asia Pac Psychiatry, 2016 Dec;8(4):260-268.
PMID: 27787964 DOI: 10.1111/appy.12210

INTRODUCTION: The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population.
METHODS: This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction.
RESULTS: The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013).
DISCUSSION: This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced*
Fulltext Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Bupropion as Treatment for Methadone-Emergent Sexual Dysfunction in Men

Yee A, Loh HS, Ong TA, Ng CG, Sulaiman AH

Am J Mens Health, 2018 Sep;12(5):1705-1718.
PMID: 29973132 DOI: 10.1177/1557988318784152

Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of "much/very much improved" (CGI-SF score = 2) was reported by 58.3% ( n = 21/36) of bupropion SR-assigned versus 27.7% ( n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced*
Effect of quercetin on cadmium chloride-induced impairments in sexual behaviour and steroidogenesis in male Wistar rats

Ujah GA, Nna VU, Agah MI, Omue LO, Leku CB, Osim EE

Andrologia, 2018 Mar;50(2).
PMID: 28703286 DOI: 10.1111/and.12866

Cadmium chloride (CdCl2 ) has been reported to cause reproductive toxicity in male rats, mainly through oxidative stress. This study examined its effect on sexual behaviour, as one of the mechanisms of reproductive dysfunction, as well as the possible ameliorative effect of quercetin (QE) on same. Thirty male Wistar rats (10 weeks old), weighing 270-300 g, were used for this study. They were either orally administered 2% DMSO, CdCl2 (5 mg/kg b.w.), QE (20 mg/kg b.w.) or CdCl2 +QE, once daily for 4 weeks, before sexual behavioural studies. The 5th group received CdCl2 for 4 weeks and allowed 4-week recovery period, before sexual behavioural test. Rats were sacrificed after sexual behavioural studies. The blood, testis and penis were collected for biochemical assays. Cadmium increased mount, intromission and ejaculatory latencies, but reduced their frequencies, compared to control. Serum nitric oxide increased, while penile cyclic guanosine monophosphate reduced in the CdCl2 -exposed rats, compared to control. CdCl2 increased testicular cholesterol, but reduced 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD activities, and testosterone concentration. QE better attenuated these negative changes compared to withdrawal of CdCl2 treatment. In conclusion, CdCl2 suppressed steroidogenesis, penile erection and sexual behaviour, with poor reversal following withdrawal, while QE attenuated these effects.

Matched MeSH terms: Sexual Dysfunction, Physiological/chemically induced