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For example, rats that engaged in the hippocampus-dependent Morris water maze had more neurogenesis in the dentate gyrus than did rats engaging in a cued version of the water maze that is hippocampus independent 139,140,141. Similarly, decreased performance on spatial memory tasks correlates with decreased adult neurogenesis among aged rodents 8,134,135. It has long been known that the hippocampus plays a critical role in spatial memory formation 128,129,130, and so it is not surprising that most work testing the function of hippocampal neurogenesis has involved testing rodents in spatial memory tasks . Middle-aged male mice (10–12 months old) given estradiol implants showed an increase in cell proliferation and new neuron production (DCX-expressing cells) but no change in 21-day cell survival . However, blocking DHT production using finasteride caused a decrease in both cell proliferation and DCX-expressing cells within the hippocampus of male mice . DCX is expressed during the cellular migration of synaptic integration stages of development , suggesting that testosterone may influence this critical period.
Men who watch sexually explicit films also report increased motivation and competitiveness, and decreased exhaustion. Men who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. Every mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a novel female. Therefore, these mammals may provide a model for studying clinical populations among humans with sexual arousal deficits such as hypoactive sexual desire disorder. The plasma levels of various steroids significantly increase after masturbation in men and the testosterone levels correlate to those levels. Sexual arousal and masturbation in women produce small increases in testosterone concentrations. Testosterone levels follow a circadian rhythm that peaks early each day, regardless of sexual activity.
Emerging evidence from preclinical models, observational studies, and small-scale prospective studies have demonstrated the potential link between AR signaling in the pathogenesis of these conditions. However, there is a notable absence of comprehensive data regarding the benefit and safety outside of the cardiovascular system. Table 2 summarises the various TRT preparations and their side effects. It is advised to do an individualized risk assessment along with shared decision making with each patient 76, 77.
However, 30 days of a high physiological dose of testosterone (0.500 mg/rat) enhanced neurogenesis , which would suggest that different doses of testosterone influence the different stages of neurogenesis in different ways. Similarly, high doses of the testosterone analogue 19-nortestosterone caused a significant decrease in 5-day cell survival in the dentate gyrus . Given that no sex differences in neurogenesis were observed, it is reasonable to conclude that variables other than sex steroids (e.g., stress hormones, age, or diet) can have an over-riding influence on seasonal changes in neurogenesis in wild rodent populations . These seasonal differences in hippocampal volume may be a result of testosterone’s effect on new cell survival within the dentate gyrus. These transgenic animals showed a significant increase in neurogenesis within the accessory olfactory bulbs in response to exposure to male urine , a response not observed in wild type males but typical of wild type female mice. Considerable evidence indicates that newly generated neurons in the olfactory bulbs play a critical role in odor discrimination broadly and pheromonal signaling among adults in particular 6,83. It is unclear whether the difference between the two studies is due to the species used or the developmental stage tested (the mice were tested at 6-8 months old, whereas the rats were only one month old).
This result contradicts findings that an acute dose of estradiol has no effect on cell proliferation among mice or voles 97,104,108, and this discrepancy may be due to either an age effect (young vs. middle-aged) or duration of dosing. This leads to the exciting possibility that short-term testosterone exposure could enhance neural plasticity during a critical time window and, in turn, facilitate memory formation. Furthermore, environmental enrichment increased network connectivity for new hippocampal neurons among mice that were exposed to the enrichment during a critical period when new neurons were 2–6 weeks old . The testosterone metabolite 3α-androstanediol has been shown to be a positive allosteric modulator of GABAA receptors , and so perhaps 3α-androstanediol enhances GABAergic signaling onto newly generated neurons to, in turn, enhance their survival. As the dendritic arbor grows during the later stages of development, the newly developed neurons receive excitatory glutamatergic input from the entorhinal cortex and send glutamatergic signals to the CA3 region , and so testosterone may influence neurite extension in some way.

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