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Effects of smoking, alcohol and drug abuse on spermatogenesis (left) and hormonal parameters (right) in males
Source publication
In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on th...
Citations
... Infertility is defined as the inability to achieve a natural conception after 12 months of regular unprotected sexual intercourse. It's estimated that a male factor contributes to infertility in approximately half of the cases [3]. Thus smoking cessation is most certainly advised for men in order to improve their reproductive outcomes due to chemicals in cigarette smoke [4]. ...
Objective
It has been established that male cigarette smoking has a negative effect on the semen quality and that it can induce DNA damage leading to worsening of reproductive outcomes. The aim of our large retrospective study is to determine the influence of male cigarette smoking on assisted reproduction, more specifically in IVF and ICSI outcomes.
Materials and methods
Our study included all consecutive infertile couples (with a nonsmoking female partner) having their first IVF/ICSI cycle. All patients had smoking assessment. Smokers were further classified into mild (1–10 cigarettes/day), moderate (11–20 cigarettes/day) or heavy smokers (>20 cigarettes/day). The primary outcome was live birth rates (LBR).
Results
The overall number of patients analyzed was 4004 and among them 433 (10.8%) were smokers. Baseline characteristics, such as female age and BMI differed significantly between nonsmokers and smokers. The crude analysis showed higher positive hCG and LBR in smokers (positive hCG 28.34% in nonsmokers vs 33.95% in smokers, p = 0.015; LBR 23.55% in nonsmokers vs 28.64% in smokers, p = 0.019) However after adjustment for relevant confounders (female age, BMI, cause of infertility, number of oocytes retrieved, insemination procedure, number of embryos transferred and day of embryo transfer) the smoking status was not significantly associated with fresh LBR (OR = 1.16, CI = 0.92–1.48; p = 0.2). The results were replicated after classification of smoking into mild/moderate/heavy [OR for nonsmokers (reference category) vs. mild vs. moderate vs. heavy= 1, 1.17, 1, 2.99; p = 0.18)].
Conclusion
Male smoking does not seem to impair live birth rates in patients undergoing IVF/ICSI treatment.
... The impact of drugs of abuse on reproductive systems varies depending on the substance and duration of use, affecting both males and females. Common effects include hormonal imbalances, reduced fertility, and complications during pregnancy [39,64]. ...
Drug abuse presents a significant global health challenge as the illicit drug market progresses from classic drugs to a growing prevalence of New Psychoactive Substances (NPS), particularly synthetic cathinones, which, although illegal, are often falsely marketed as safe and legal alternatives. The rapid increase in the use of these drugs complicates the assessment of their safety and effects on human health. However, they pose unique toxicological concerns that remain largely uncharacterized. This study investigated the toxic effects of three synthetic cathinones, namely, methylone, pentedrone, and 4-methylethcathinone (4-MEC), using the model organism C. elegans. We assessed the impact of these substances on animal survival, development, reproductive behavior, and longevity. Our results showed that short-term exposure (24 h) to concentrations of 5.0 mM or higher significantly reduced animal survival rates, while prolonged exposure (72 h) led to more pronounced toxicity, significantly reducing survival rates at concentrations as low as 1.0 mM. Moreover, sublethal concentrations resulted in developmental arrest. Additionally, pentedrone impaired reproductive capacity, while 4-MEC significantly shortened C. elegans lifespan. These findings highlight the urgent need for further investigation into the implications of synthetic cathinone use on human health through in vivo models as their prevalence in the illicit drug market continues to rise.
... Several adverse effects have been linked to drug abuse in males, including impotence (Onyije 2012), diminished sexual interest (Ajayi and Akhigbe 2020), gynecomastia (Rahnema et al. 2014) and testicular atrophy (Fronczak et al. 2012). Drug abuse has also been reported to have detrimental impact on the maturation of the male reproductive system which also impacts fertility (Sansone et al. 2018;Schifano et al. 2022). Furthermore, research has shown that over-the-counter antihistamines may negatively impact normal testicular function (Hamed et al. 2023). ...
Promethazine is a pharmacological compound classified as a first-generation antihistamine. It is often used in the treatment of a range of medical ailments, including allergies, insomnia and the common cold. The primary objective of this study was to evaluate the impact of promethazine on the structural integrity of the testes, levels of testosterone in the circulatory system, the process of spermatogenesis and the quality of sperm. This study aim to investigate the potential involvement of oxidative stress-dependent pathway, cytokines, caspase-3 and xanthine oxidase activities and uric acid levels. A total of twenty adult male Wistar rats were randomly assigned to two groups, each consisting of ten rats. The control group was given 0.5 ml of distilled water orally as a vehicle for a duration of 56 days. The promethazine-treated group, on the other hand, received a dosage of 50 mg/kg of promethazine hydrochloride over the same 56-day period. The administration of promethazine resulted in compromised steroidogenesis and spermatogenesis, ultimately leading to diminished sperm quality. Concomitant with this phenomenon, there was an increase in the indicators of testicular damage, oxidative stress, xanthine oxidase/uric acid levels, inflammation and apoptosis. Furthermore, there was a notable decrease in the functioning of enzymatic antioxidants in the testicles. A change in testicular cytoarchitecture, as well as a decrease in both absolute and relative testicular weight, accompanied these modifications. Therefore, it may be deduced that promethazine elicits testicular harm via the overexpression of xanthine oxidase and uric acid, as well as the activation of caspase-3 through an oxidative-sensitive signaling route.
... The mixture or concoction is also known as "syrup," "sizzurp," "barre" and "lean" (nicknamed for the posture that its users assume when intoxicated), (Agnich et al., 2013). Couple infertility, which is defined by the failure to achieve pregnancy after at least 12 months of regular, unprotected intercourse, (Sansone et al., 2018) is a reoccurring societal problem facing the nations having approximately half of its cases caused by factors related to the male partner (Miyamoto et al.,2011). However, exposure to certain drugs and the recreational use of illicit drugs has been reported to be a major contributor to male factor infertility with marijuana, opioid narcotics, methamphetamines, cocaine, and anabolic-androgenic steroids (AAS) topping the list (Amini et al, 2014;Fronczak et al., 2012). ...
BACKGROUND AND AIM: Studies have shown that given its sedating and euphoric effects and the development of tolerance within a relatively short time-frame on repeated use, codeine and codeine-containing products carry identified abuse potential both in pill and syrup forms. Its use, misuse and dependence have become an emerging global public health concern. Accordingly, this study investigated the effect of codeine containing cough syrup on the testes of adult Wistar rats. METHODOLOGY: Twenty rats (110-200g) were divided into four groups A-D of five rats each. Group A (control) received only feed and water. Group B (low dose group) received 10.95mg/kg body weight, group C (medium dose group) received 21.90mg/kg body weight while group D (high dose group) received 43.80mg/kg body weight of the syrup daily via an oral cannula for eight weeks. At the end of the experiment, the testes were harvested, weighed and processed for seminal and histological assessments. RESULTS: Only the low dose group had significantly (P<0.05) lower values of seminal analysis when compared to the control. No deleterious effects were observed in the histological profiles of all the testes. CONCLUSION: Taken together, these results provide preliminary evidence from seminal analysis and histology that codeine-containing cough syrup had no adverse effect on the testes.
... The mixture or concoction is also known as "syrup," "sizzurp," "barre" and "lean" (nicknamed for the posture that its users assume when intoxicated), (Agnich et al., 2013). Couple infertility, which is defined by the failure to achieve pregnancy after at least 12 months of regular, unprotected intercourse, (Sansone et al., 2018) is a reoccurring societal problem facing the nations having approximately half of its cases caused by factors related to the male partner (Miyamoto et al.,2011). However, exposure to certain drugs and the recreational use of illicit drugs has been reported to be a major contributor to male factor infertility with marijuana, opioid narcotics, methamphetamines, cocaine, and anabolic-androgenic steroids (AAS) topping the list (Amini et al, 2014;Fronczak et al., 2012). ...
BACKGROUND AND AIM: Studies have shown that given its sedating and euphoric effects and the development of tolerance within a relatively short time-frame on repeated use, codeine and codeine-containing products carry identified abuse potential both in pill and syrup forms. Its use, misuse and dependence have become an emerging global public health concern. Accordingly, this study investigated the effect of codeine containing cough syrup on the testes of adult Wistar rats. METHODOLOGY: Twenty rats (110-200g) were divided into four groups AD of five rats each. Group A (control) received only feed and water. Group B (low dose group) received 10.95mg/kg body weight, group C (medium dose group) received 21.90mg/kg body weight while group D (high dose group) received 43.80mg/kg body weight of the syrup daily via an oral cannula for eight weeks. At the end of the experiment, the testes were harvested, weighed and processed for seminal and histological assessments. RESULTS: Only the low dose group had significantly (P<0.05) lower values of seminal analysis when compared to the control. No deleterious effects were observed in the histological profiles of all the testes. CONCLUSION: Taken together, these results provide preliminary evidence from seminal analysis and histology that codeine-containing cough syrup had no adverse effect on the testes.
... Azari and colleagues [30] found a significant link between chronic tramadol administration and impaired quality of sperm parameters, including a decrease in sperm count, motility and vitality in mice. It is important to note that the effect of tramadol and vitamin D3 co-administration on semen parameters seen in this present study is concomitant with the observed effect on the serum testosterone levels, which also showed no significant effect across all groups, even though previous research has shown that tramadol or its opioid equivalents can significantly reduce testosterone levels [31][32][33][34][35][36][37]. Previous studies and this current study may differ in their effects due to the relatively short study duration or the administered tramadol dose. ...
Background:
Tramadol, an opioid analgesic, is known to induce testicular damage and impair reproductive parameters. Vitamin D3, recognized for its antioxidant and protective properties, might offer a potential protective effect against tramadol-induced testicular damage. This study observed the effects of co-administration of vitamin D3 and tramadol on serum kisspeptin levels, testicular histology, semen parameters, testosterone levels, and oxidative stress markers in male rats.
Methods:
Fifteen male rats weighing between 150 and 250 g were randomly divided into three groups (n = 5 per group). Group A was the control, receiving only distilled water. Group B was administered 20 mg/kg body weight of tramadol daily, while group C received both 20 mg/kg body weight of tramadol and 25 μg/kg body weight of vitamin D3 daily. The treatments were administered orally for 14 days. Post-administration body weight, relative testicular weight, serum kisspeptin levels, semen parameters, testosterone levels and oxidative stress markers (catalase, glutathione and malonaldehyde) were measured. Testicular histology was also examined using photomicrography.
Results:
No significant differences were observed in body weights, relative testicular weights, serum kisspeptin levels, semen parameters, testosterone levels, or oxidative stress markers among the experimental groups (p > 0.05). Histological analysis in the tramadoltreated group exhibited significant degradation of spermatozoa, which was not mitigated by vitamin D3 co-administration compared to the control group.
Conclusions:
The study demonstrates that vitamin D3 supplementation does not significantly ameliorate tramadol-induced testicular damage. There is a need for further research with varied doses and longer durations to further explore the potential protective mechanisms of vitamin D3.
... Adequate evaluation of health promoting lifestyles should be offered to everybody by midwifes and other healthcare specialists, at the latest when attending fertility clinics. And as one review found out, discontinuing smoking and alcohol use should be suggested to all who are undergoing investigation for infertility in order to provide the best outcomes [9]. ...
... A review article on smoking and alcohol addiction concluded that these habits influence men´s fertility in a negative way [9]. Another review by Balawernder and Orkisz also indicated that the most significant factors that cause male infertility are lifestyle-related; being obese, nicotine addiction and alcohol consumption among others [17]. ...
... Earlier studies have shown an association between alcohol consumption and fertility; for example, the time to pregnancy is longer and testosterone levels lower [9,10,17]. In the previous Finnish study hangovers were associated with infertility among women [19]. ...
Background
The aim of this population-based study is to examine lifestyle factors (smoking and alcohol consumption) and body mass index (BMI) among fertile and infertile Finnish women and men.
Methods
Infertility was defined based on reporting having ever tried to become pregnant or to get a child unsuccessfully over a year. Logistic regression analysis was used to investigate the association of smoking, alcohol consumption and BMI with infertility when adjusted first for age and then additionally for marital status, education and employment status. Men (n = 201) and women (n = 267) who had ever experienced infertility were compared to those with no experience of infertility (n = 1677 men and n = 1257 women) and further separately for those who had despite the infertility experience received a child or not.
Results
No significant differences between smoking or BMI were found in men by the infertility experience, compared to childless infertile and infertile men with a child. However, men with infertility experience had higher total alcohol consumption (g/year) than fertile men (p = 0.005). The odds ratio for total consumption of alcohol at an average or high level was 2.49 (95% CI 1.39–4.45) in the age adjusted model and 2.01 (CI 1.11–3.67) in the fully adjusted model for males who had experienced infertility by using the fertile men as a reference group. No differences in smoking, alcohol consumption or BMI were found between women with or without infertility experience.
Conclusions
The results indicate that in fertility counselling and care given by midwifes and health care professionals, attention should be paid to men’s lifestyle, especially to alcohol consumption. The small numbers of those having experienced infertility limited analyses in this study.
... Primary infertility: Is de ned as the inability to conceive at all (i.e., no previous history of pregnancy) (2,41,42). ...
... Secondary infertility: Is de ned as the inability to conceive after a previous pregnancy, with or without a live birth (2,42). Psychological stress of infertility: any psychological problems related to social, depression, and stress to fertility-related treatment (41,43). ...
Background: Infertility and infertility induced psychological stress are the major reproductive health problem that women across the globe are facing. The problem is more pronounced in developing countries. In Ethiopia, this is coupled with the scarcity of specialized fertility treatment centers which provide treatment and care for infertility. There is limited knowledge regarding the psychological stress experienced by infertile women in Ethiopia, particularly among infertile women seeking treatment from specialized infertility treatment centers.
... Male infertility occurs concurrently with diabetes mellitus, cardiovascular disorder, high blood pressure, chronic liver disease and vitamins deficiency [5][6][7][8] . Drug misuse, excessive stress, environmental hazards are also reported in many cases of male infertility [9][10] . ...
Human sex hormone binding globulin (SHBG) is a glycoprotein produced and secreted by the liver and is capable of binding androgens and estrogens in males. Both androgens and estrogens are important hormones that help in the development of sexual and reproductive tissues. The present work investigates the active chemical components of Aframomum melegueta (Alligator pepper) as well as study their involvement as potential drug lead to inhibiting Sex hormone binding globulin (SHBG) receptor protein that is involved in the various cases of male infertility. Phytochemical identification of the constituents was achieved by Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrophotometry GC-MS experiments, while the ligand-target interaction to discover the drug lead candidates was achieved by molecular docking. Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) screening was performed to ascertain the suitability of the compounds as drug lead candidates. The GC-MS result revealed a total of 30 compounds, the molecular docking results showed that 5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one which was found to be present in 43.2511%, gave a binding energy of-7.0 Kcal mol-which is an indication that it might form a good drug lead candidate for the inhibition of the Sex hormone binding globulin. The ADMET study showed that all the compounds above 1% from the GC-MS study proved leading drug candidates with great efficacy, no toxicity, no cardiotoxicity and no carcinogenicity was observed.
... The affected proteins were associated with energy metabolism, reproduction and the development of structural molecules (Chen et al., 2015). Elevated levels of ROS following smoking can disturb male fertility via damage to sperm DNA, lipid peroxidation and impaired spermatogenesis (Calogero et al., 2023;Kumar et al., 2015;Sansone et al., 2018;Wright et al., 2014). ...
Substance use refers to the consumption of drugs that have varying degrees of impact on a persons’ physical, mental and emotional well-being. While the adverse health effects of drugs have been extensively documented, further research is needed to understand their impact on fertility. Studies have indicated that substance use affects both the male and female reproductive systems. As substance use is more prevalent among young adults compared with the elderly, it appears that individuals of reproductive age are particularly vulnerable to the reproductive impairments associated with substance use. Although numerous studies have reported detrimental effects of substance use on pregnant women and their foetus during the post-implantation stages, there are limited studies on critical pre-implantation period and gamete stages. In this narrative review, we aimed to focus on the most significant evidence regarding the impact of substances on gametes and pre-implantation embryos.
