Rinaldi et al. showed that intake of alcohol increased serum levels of dehydroepiandrosterone sulphate, testosterone, androstenedione and oestrone compared with non-consumers women(Reference Rinaldi, Peeters and Bezemer36,Reference Shafrir, Zhang and Poole37) . Mona et al. showed that NAC administration before the chemotherapy could improve reproductive functions and the gonadal hormone disturbance in female rats through its protective effects against oxidative stress(Reference Helal30). Pooled analysis of eighteen randomised clinical trials with a total population of 3161 in the current study revealed that NAC supplementation had significant increasing and decreasing effects on FSH and TT levels, respectively. N-Acetyl Cysteine (NAC) is a supplement derived from the amino acid L-cysteine. The question of does NAC decrease testosterone? Moreover, NAC has a positive effect on sperm concentration and ejaculate volume, whereas no obvious effect in serum hormones. However, the studies included in this study are all RCTs, which increases the strength of the research results. There are deficiencies in the quality of the trials used for analysis, mainly including fewer trials included and inconsistent basic indicators of various studies. Jannatifar et al. (2019) reported that the concentration of seminal malondialdehyde (MDA) decreased significantly, and MDA was a specific marker of lipid peroxidation, while TAC increased significantly after NAC treatment. Khan et al. (2013) reported that the level of total antioxidant capacity (TAC) in seminal plasma of patients with asthenospermia was significantly lower than that of healthy men. Spermatogenesis is highly controlled by hormonal environment, in addition to affecting the speed and quality of spermatogenesis; any change of hormone distribution may profoundly affect the chromosome ploidy and the integrity of sperm chromatin (Safarinejad & Safarinejad, 2009). NAC, inulin, and the combined therapy reduced the mean fluorescence intensity of GFAP positive cells in ORX rats (Figure 4I). All treatments decreased cell size of GFAP positive cells in ORX rats (Figure 4G). An increase in cell volume of GFAP positive cells in ORX rats was observed in ORX rats, when compared with sham-operated rats. All treatments equally increased microglial ramifications (Figures 3K and L). All treatments equally decreased p-NFĸb/ total-NFĸB ratio in ORX rats (Figure 2E). These parameters were restored to within normal limits by testosterone replacement, NAC, inulin, and the combined therapy (Figure 2C and D). Therefore, the present meta-analysis aimed to evaluate the effects of NAC supplementation on infertility parameters such as ovulation biomarkers and serum levels of sex hormones in women with PCOS. It has been also revealed that levels of hormones and spermatogenesis were not different among adult male Wistar rats following NAC consumption(Reference Shahrzad, Shariati and Naimi15). The present study assessed the effects of NAC supplementation on semen parameters and antioxidant status in asthenoteratozoospermic men partners of infertile couples. NAC may be less toxic and more soluble than l-cysteine itself, which is why NAC is often used in supplements instead of l-cysteine by itself. So, increasing l-cysteine supply can increase this rate. Scientists believe that the supply of l-cysteine in the cell limits the rate of glutathione production in the body. The body then uses l-cysteine to make glutathione, which is a tripeptide or chain of amino acids composed of cysteine, glycine, and glutamic acid. In the body, NAC converts to l-cysteine, a nonessential amino acid. Recently, our previous study reported that both microglia and astrocytes also had an amoeboid-like shape in castrated male rats similar to this study . A previous study showed negative microglial morphological changes in high fat diet-fed rats, which were improved with prebiotic, probiotic and synbiotics treatment . Testosterone replacement, NAC, inulin, or the combined therapy in ORX rats equally ameliorated cognitive decline, possibly through anti-oxidative and anti-inflammatory effects of these therapies. These changes led to further brain oxidative stress 28,29, brain inflammation, and microglial activation 11,29,30, resulting in cognitive decline, as shown in the present study. Testosterone replacement, NAC, inulin, and the combined therapy attenuated hippocampal dysplasticity, leading to the improvement of cognition in testosterone-deprived condition. Testosterone replacement, NAC, inulin, and the combined therapy equally improved cognitive function as indicated by the decreased time taken to reach the platform in the acquisition test and the increased time spent in the target quadrant during the probe test in ORX rats (Figure 7C-E). No, NAC does not directly increase testosterone production. Does NAC directly increase testosterone production? Based on available evidence, the answer to the question, does NAC decrease testosterone? Its role is primarily supportive, helping the body recover and potentially aiding in the restoration of natural testosterone production. NAC is sometimes used during post-cycle therapy (PCT) due to its antioxidant and liver-protective properties. After a cycle of anabolic steroids, individuals often experience a suppression of their natural testosterone production. It’s best to start with a lower dose and gradually increase it as needed, monitoring for any side effects.