One of the most common treatments for gender reassignment, feminizing hormone therapy or androgen gender affirming therapy, which is often used in transgender women and non-binary people to promote the physical changes caused by female hormones during puberty,” reprograms” breast tissue in transgender men.
For the first time, a team of researchers coordinated from the University of California-San Francisco (USA) has examined the effects of this androgen therapy on breast tissue in transgender men and the results, which are published in Cell Genomics, contribute a unprecedented look to the changes that occur as a result of this therapy, a common and highly effective form of transgender care.
In addition, the information from this study may have implications for the breast cancer treatment in all populations as it shows that the therapy causes gene expression in mammary cells to be silenced and male genetic programs are activated.
Breast cancer rates are known to be lower in transgender men, and recent studies have shown that activation of androgen receptors may have antitumor activity in certain types of breast cancer.
In this study, the researchers found that androgen therapy suppressed the expression of genes involved in breast cancer with BRCA mutation. Overall, “this indicates that androgen receptor activation may be a valid preventive or therapeutic strategy for ER+ breast cancer and, in agreement, clinical trials testing androgen receptor activation in this subtype have been implemented.” the authors write.
Feminizing hormone therapy is used to change your hormone levels. Those hormonal changes cause physical changes that help match a person’s gender identity and body. The goal of this therapy is to help match a person’s gender identity and body..
“Many of the gene expression changes induced by androgen therapy were also consistent with male-specific sex biases discovered by comparing breast tissues and other organs from cisgender men and women,” the researchers write. [Un persona cisgénero es aquella cuya identidad y expresión de género coincide con su sexo biológico].
This includes increased expression of the CUX2 gene, which has the highest expression in the prostate, as well as elevated levels in the liver and breast tissues of cis men compared to tissues of cis women.
The researchers obtained breast tissue from mastectomies of transgender men who had undergone androgen therapy and compared it with breast tissue of cisgender women obtained by cosmetic breast surgery. For each tissue type, they characterized the associated changes in gene expression and cell-cell interactions taking into account the spatial profile of the cells.
In trans male tissues, found that cells expressing hormone receptors had been reprogrammed by androgensand these cells then relayed the effects to nearby cells via paracrine signaling relays.
Androgen receptor activation may be a valid preventive or therapeutic strategy for ER+ breast cancer
They found that trans-male cells were silenced compared to cis-female cells, showing fewer molecular markers and unique genes. While cis-female cells showed gene expression associated with growth factors and mammary gland development, trans-male cells showed expression associated with fatty acid metabolism and calcium signaling.
Within the samples of cis women, the researchers looked at those of cis women premenopausal and postmenopausal.
Compared to trans male tissue, the differences between these two tissue types were minuscule, indicating that the changes in the trans male breast likely occur not only due to the cessation of estrogen production by the ovaries, but also directly due to androgens.