Plain Language Summary
Gender identity is an important issue in society, yet its causative mechanism is poorly understood. The main anatomical differences between males and females are the genitalia and the brain. This paper reviewed the literature to explore the link between genetic influences and brain development, and their impact on gender identity. Investigating these developmental mechanisms could lead to advances in the understanding of gender dysphoria, a condition whereby an individual’s gender and biological sex are mismatched. Exploring the biochemical development of the genitalia highlights the differences between males and females, notably how testosterone elicits the pathways of male development in an embryo. When research has been conducted in people with Androgen Insensitivity Syndrome, a condition where the testosterone receptor is mutated and faulty, and thus cannot function, gender dysphoria is observed as the body is genetically male but anatomically female.It is known that the structure of male and female brains differs; it is found that people with gender dysphoria have a brain structure more comparable to the gender to which they identify. The review of the literature suggests that there is a disparity between the brains of those who identify differently to their assigned gender at birth, highlighting a multifactorial underpinning of the gender identity. Further research is required to shed light on the molecular mechanism of this, allowing for greater education and understanding of this scientific and social phenomenon.
The Endocrine Society. Transgender Health An Endocrine Society Position Statement 2020-12 https://www.endocrine.org/advocacy/position-statements/transgender-health \cite{endocsoc}
Abstract : There is a durable biological underpinning to gender identity that should be considered in policy determinations . Medical intervention for transgender youth and adults (including puberty suppression, hormone therapy and medically indicated surgery) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care. Federal and private insurers should cover such interventions as prescribed by a physician as well as the appropriate medical screenings that are recommended for all body tissues that a person may have. Increased funding for national pediatric and adult transgender health research programs is needed* to close the gaps in knowledge regarding transgender medical care and should be made a priority.
*NOTE: Remember what I said about how studies always or almost always will say further study is needed. This one is pretty upfront about why. We need money.
Amir, Hadar / Perl, Liat / Barda, Shimi / Lantsberg, Daniel / Becker, Anat Segev / Israeli, Galit / Azem, Foad / Oren, Adolescent Transgender Females Present Impaired Semen Quality That Is Suitable for Intracytoplasmic Sperm Injection Even Before Initiating Gender-Affirming Hormone Treatment 2022 Reproductive Sciences , Vol. 29 p. 260-269 https://doi.org/10.1007/s43032-021-00561-y \cite{Amir2022}
Abstract: The present study aimed to determine the semen quality and cryopreservation outcomes among adolescent transgender females at the time of fertility preservation (FP) before initiating gender-affirming hormone (GAH) treatment. This retrospective cohort study included 26 adolescent transgender females who underwent FP in our Fertility Institute between 06/2013 and 10/2020. Pre-freezing semen parameters were compared to WHO 2010 reference values. Post-thaw semen parameters were used to determine the adequate assisted reproductive technology (ART). A multivariate linear regression analysis was performed to assess the impact of medical and lifestyle factors on semen quality. The mean age at which adolescent transgender females underwent FP was 16.2 ± 1.38 years. The median values of all semen parameters in our study group were significantly lower compared to the WHO data, including volume (1.46 mL vs 3.2 mL, respectively, P = 0.001 ), sperm concentration (28 × 106/mL vs 64 × 106/mL, P < 0.001), total sperm number (28.2 × 106 vs 196 × 106, P < 0.001), total motility (51.6% vs 62%, P < 0.001), and normal morphology (2% vs 14%, P < 0.001). The frequency of semen abnormalities was teratozoospermia 72%, hypospermia 52%, oligozoospermia 28%, and azoospermia 4%. The median post-thaw total motile count was 0.17 × 106/vial, and the quality was adequate only for ICSI in 87.7% of the thawed semen samples. No correlation was found between selected medical and lifestyle factors and poor semen parameters. Semen quality is strongly reduced among adolescent transgender females before hormone therapy and their stored sperm samples are suitable for intracytoplasmic sperm injection (ICSI) rather than conventional IVF/intrauterine insemination (IUI).
Findings in sports medicine.
Hilton, Emma N. / Lundberg, Tommy R. Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage2020 Sports Medicine https://doi.org/10.1007/s40279-020-01389-3 \cite{Hiltona}
Abstract: Males enjoy physical performance advantages over females within competitive sport. The sex-based segregation into male and female sporting categories does not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee (IOC) determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been scrutinized. Here, we review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage and thus delivers fair and safe competition. We report that the performance gap between males and females becomes significant at puberty and often amounts to 10–50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and explosive strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 12 months of treatment . Thus, the muscular advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations should consider this evidence when reassessing current policies regarding participation of transgender women in the female category of sport.
The British medical journal conducted a large study of people who began hormone therapy as adults, female to male and male to female. While two years of cross sex hormone therapy did reduce muscle strength and mass a speed advantage was retained. Hilton EN and Lundberg T R published a paper which was well cited that stated a much larger advantage, but this was latter corrected by the journal due to undeclared conflict of interest.
Note in the following subsection, as the science is softer all findings pro and against trans inclusion bear a degree of opinion and point of view. The above chemical (DNA) and MRI and other laboratory findings do not have that issue.
Roberts, Timothy A. / Smalley, Joshua / Ahrendt, Dale, Effect of gender affirming hormones on athletic performance in transwomen and transmen: implications for sporting organisations and legislators, 2021 British Journal of Sports Medicine , Vol. 55, No. 11 British Association of Sport and Excercise Medicine p. 577-583 https://doi.org/10.1136/bjsports-2020-102329 \cite{Roberts577}
Abstract: Objective To examine the effect of gender affirming hormones on athletic performance among transwomen and transmen.Methods We reviewed fitness test results and medical records of 29 transmen and 46 transwomen who started gender affirming hormones while in the United States Air Force. We compared pre- and post-hormone fitness test results of the transwomen and transmen with the average performance of all women and men under the age of 30 in the Air Force between 2004 and 2014. We also measured the rate of hormone associated changes in body composition and athletic performance.Results Participants were 26.2 years old (SD 5.5) . Prior to gender affirming hormones, transwomen performed 31% more push-ups and 15% more sit-ups in 1 min and ran 1.5 miles 21% faster than their female counterparts. After 2 years of taking feminising hormones, the push-up and sit-up differences disappeared but transwomen were still 12% faster. Prior to gender affirming hormones, transmen performed 43% fewer push-ups and ran 1.5 miles 15% slower than their male counterparts. After 1 year of taking masculinising hormones, there was no longer a difference in push-ups or run times, and the number of sit-ups performed in 1 min by transmen exceeded the average performance of their male counterparts.Summary The 15–31% athletic advantage that transwomen displayed over their female counterparts prior to starting gender affirming hormones declined with feminising therapy. However, transwomen still had a 9% faster mean run speed after the 1 year period of testosterone suppression that is recommended by World Athletics for inclusion in women’s events . A de-identified copy of the data is available from the corresponding author upon reasonable request.
Hilton, Emma N. / Lundberg, Tommy R. CORRECTION To: Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage 2021 Sports Medicinehttps://doi.org/10.1007/s40279-020-01389-3 \cite{Hilton}
Abstract: After publication of this article, concerns were raised regarding potential undeclared conflicts of interest . In light of this the authors have provided the following statement: EH and TL have given talks and engaged in the mainstream media and academic press regarding the biology of sex and how they have concluded that this should impact sporting categories. All dissemination or engagement, irrespective of the medium, has been guided by their education, disciplinary training, and research findings. The authors assert that this does not constitute a conflict of interest. Rather, it is an essential part of their academic freedom and their obligation to engage, publicly, in such discussions.
(See for example: Harder, better, faster, stronger: why we must protect female sports by Hilton. “Male puberty and testosterone. Testosterone, the androgen driving male physical development, is a wonderful hormone. It is responsible for advantageous skeletal features that develop during male puberty, such as increased height, increased bone size and density, longer limbs,” In short in a field of science where one can select data in such a way as to create a certain result she selected top tier athletes and only transgender people who transitioned as adults, post puberty not during puberty age. The second point is a weakness of all of the studies in this section and seems to be a standard practice. Which is why I searched out the British Association of Sports Medicines unconflicted study that partially agrees with hers. This leaves open the question what of transgender people who started hormones very young and who have little or no advantage or disadvantage?)  This researchers mind was totally made up before she started, and she also did not disclose this fact to the reviewers. 
British Journal of Sports Medicine, Plain language findings and  expert opinion.
Testosterone and Transgender Athletic Performance : Finding a path for inclusion for transgender athletes by BJSM https://blogs.bmj.com/bjsm/2021/01/22/testosterone-and-transgender-athletic-performance-finding-a-path-for-inclusion-for-transgender-athletes/ \cite{BJSM}
Transgender individuals have been able to serve openly and have access to gender affirming hormone therapy in the United States military since 2016. In the Air Force, requests to begin or continue hormonal therapy are reviewed by a centralized clinic. Of the 222 transgender service members who requested permission to start or continue treatment, we had complete fitness and medical data on 46 transwomen and 29 transmen. The average age was 26.2 with a standard deviation of 5.5 years.
For transmen, there was no significant change in body composition (as measured by height, weight, and waist circumference) over time. They were able to perform the same number of sit-ups as cismen prior to hormone therapy and improved with therapy. Push-ups and run times reached that of cismen by the 1-year point.
For transwomen undergoing hormone therapy, there was an increase in weight over time but no change in waist circumference. Push-ups and sit-ups equalized with ciswomen by the 2-year mark. However, transwomen still retained an advantage in run times on the mile and a half run compared to the average time for ciswomen 2 ½ years after starting medical transition
What does this mean?
In elite level or collegiate athletic competition, where a 1-2% advantage in speed or strength is often the difference between victory and defeat, governing bodies need to re-examine guidelines for inclusion of transgender and other women with elevated testosterone levels and determine what evidence-based changes are required to ensure a level playing field. They will need to stand up to legal scrutiny. In youth and recreational sports there is such a broad range of ability, training, and development that differences from prior testosterone after 12 months of suppression may not have a meaningful competitive impact and the benefits of inclusion of all athletes should take priority. When establishing guidelines for youth and recreational sports, the question has to be: “What is the best thing for all our athletes?”