**2.6 Typical approach to understanding the normative effects of androgens – sex differences, seasonal and correlational effects**

In behavioral neuroendocrinology, to determine the role of a hormone for a behavioral process, an approach is to assess endogenous changes in hormones,

#### **Figure 4.**

*Plot of smoothed age-specific population centiles (97.5, 95, 75, 50, 25, 5, and 2.5%) for serum testosterone (nmol/l; upper left), DHT (nmol/l; lower left), androgen (nmol/l; right top), and E2 (pmol/l; right lower) in 10897 samples from men aged over 35 years from population-based studies in three Australian cities (Adelaide, Perth, and Sydney) using LC–MS steroid measurements from a single lab with data analyses using GAMLSS modeling. A full color version of this figure is available at http://dx.doi.org/10.1530/EJE-15-0380.*

*Androgens' Effects across the Lifespan in Men and Animal Models DOI: http://dx.doi.org/10.5772/intechopen.96707*



#### **Figure 5.**

*Summary of effects of loss of androgens among men https://www.guidelinesinpractice.co.uk/mens-health/ testosterone-deficiency-treat-men-who-have-bothersome-symptoms/454121.articleSigns and symptoms.*

extirpation of the hormone (i.e. surgical removal of the gonads), and replacement back of a hormone. Endogenous changes are used to assess the extent to which levels of the hormone in question vary with the behavioral endpoint of interest. This is usually assessed in males by investigating behaviors and androgens that vary from: 1) females (which typically have lower levels of androgens), 2) by season (e.g. seasonal breeders), and 3) across the lifespan (post-pubertal, with androgen decline in advanced aging). One example of this type of investigation would be assessments of reproductively relevant behavior, such as aggression, among a seasonal breeder, such as a deer. Male, but not female, deer begin to grow antlers (which have utility for aggressive responding in this species) during mating season post-puberty. Aggressive behavior among male deer coincides with peak levels of androgens and is reduced during non-breeding season associated with androgens levels at nadir.

### **2.7 Typical approach to understanding the normative effects of androgens**

To begin to assess the causative role of the hormone in this behavior, the second and third approaches of extirpation and replacement are utilized; extirpation should remove the hormone and result in abolishment of the behavior and then replacement back of this hormone should reinstate the behavior. A classic example of this approach is the Berthold experiment. Although this experiment predates basic knowledge that hormones existed, it had been known for centuries in agriculture that there are clear behavioral differences in male animals when their testes were removed. Dr. Berthold is credited with completing the first systematic study (1849) of extirpation and replacement of the testes (which we now know are a main source of circulating androgens) to investigate secondary sex characteristics and reproductive behaviors of roosters. Roosters were castrated and reductions in appetitive and consummatory aspects of mating, as well as secondary sex characteristics, were abolished. This was reversed when roosters were implanted with testes. Dr. Berthold hypothesized that these changes in behavior and phenotype were due to a substance in the testes (rather than actions via nerves in the body, which was the prevailing notion at the time).

In summary, although these methods to understand effects of hormonal variations, extirpation, and replacement have a long history and have clearly contributed to our understanding of the relationship between hormones and a hormone-mediated behavior, there is also individual differences in the responses of individuals that need to be better understood. The relationship between a behavior and hormone levels may not be linear, and this relationship may be mediated by individual experience (i.e. current/prior androgen exposure), a response first noted over 60 years ago [7].
