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  5. Selective Estrogen Receptor Modifiers (SERMs) for Transmasculine Adolescents

Selective Estrogen Receptor Modifiers (SERMs) for Transmasculine Adolescents

Background

Puberty blockade is an important part of gender affirming medical care for many trans adolescents. Usually, gonadotropin releasing hormone analogues (GnRHas) would be used to inhibit pubertal changes. However, the provision of GnRHas for gender dysphoria has been severely restricted in some parts of the world, including the United Kingdom.

This article examines a potential alternative to GnRHas for transmasculine adolescents specifically. Selective estrogen receptor modifiers (SERMs) have some antioestrogenic effects that inhibit some of the pubertal changes in people with ovaries, and so could potentially have a role in the gender affirming medical treatment of transmasculine adolescents.

What are SERMs and how do they work?

SERMs are medications that were initially intended to treat conditions such as infertility, breast cancer, and osteoporosis in cis women. They include raloxifene, clomiphene, toremifene, and tamoxifen.

SERMs work by binding to oestrogen receptors at various sites in the body, including the breasts, the skin, and the reproductive organs. This alters the effects of oestrogen at these sites. Different SERMs have different bodily effects because they bind to different oestrogen receptors to different degrees.

How could SERMs be used in gender affirming medical treatment?

Raloxifene is the most commonly used SERM in gender affirming hormone treatment. It predominantly binds to oestrogen receptors in the breasts and reproductive organs. This inhibits breast growth and also inhibits menstruation, which makes it a potentially promising treatment for transmasculine adolescents.

As well as being a potential treatment for transmasculine adolescents, raloxifene may be an option for transfeminine and nonbinary people who are receiving feminising hormone treatment but do not want too much breast growth.

Tamoxifen is occasionally used to reduce breast development, but it tends to have more severe side effects than raloxifene. Toremifine and clomiphene are not generally used in gender affirming hormone treatment because they tend not to work on the oestrogen receptors that are of interest for medical transition.

What is the evidence base for SERMs in transmasculine adolescents?

As SERMs are relatively new additions to gender affirming hormone treatment, it is important to note that there are currently no studies on the use of SERMs in the trans population. Evidence for the use of SERMs in gender affirming hormone treatment comes predominantly from (1) our theoretical knowledge of the mechanisms of SERMs and (2) clinical studies on the uses of SERMs in the cis population.

Based on our theoretical knowledge of the mechanisms of SERMs, it is understood that SERMs bind to oestrogen receptors in different bodily tissues and alter the effects of oestrogen on these tissues. This mechanistic evidence suggests that SERMs may produce bodily effects that are beneficial for achieving the aims of gender affirming medical treatment (Hodax and DiVall, 2023; Xu et al., 2021).

In clinical practice, SERMs have been used to treat gynaecomastia, or unwanted breast growth, in cis male adolescents. A study found that raloxifene was effective at reducing breast growth, were tolerated well by the participants, and had no significant adverse effects (Lawrence et al., 2004). Other studies have found that tamoxifen is also safe and effective at reducing breast growth in cis male adolescents with gynaecomastia (Lapid et al., 2013; Zehetner, 2015).

SERMs have also been used to treat breast hypertrophy, or unwanted excessive breast growth, in cis female adolescents (Demir et al., 2010; O’Hare and Frieden, 2000). Again, treatment was effective and tolerated well with no significant adverse effects.

Although the above studies were in cis participants, they do provide evidence that SERMs are safe and tolerated well in adolescents. Furthermore, they provide evidence that SERMs can be effective at reducing pubertal breast growth. This makes them a promising treatment option for transmasculine adolescents who wish to inhibit some of the physiological changes of puberty, such as breast growth and development.

Are SERMs safe?

As with all medicines, SERMs do have side effects. Common side effects of raloxifene include hot flashes, muscle cramps and spasms, swelling of the hands and feet, joint pain, and tiredness.

Clinical research on the use of SERMs in cis adolescents has suggested that SERMs are generally safe and well tolerated (Demir et al., 2010; Lapid et al., 2013; Lawrence et al., 2004; O’Hare and Frieden, 2000; Zehetner, 2015).

However, there is also evidence that SERMs are associated with an increased risk of thromboembolic disease, or a blood clot in the veins (Adomaityte et al., 2008). This is estimated to occur in 1–2 out of 100 people who take it, although this figure comes from research on postmenopausal cis women who potentially have more susceptibility factors than pubertal adolescents. Hence, the risk may be lower in adolescents.

It is important to note that thromboembolic disease does not have a singular cause, but is a complex outcome of multiple interacting causal factors. These can include smoking, high cholesterol, high blood pressure, inactivity, obesity, and recent surgery. You can reduce your risk of thromboembolic disease by addressing any risk factors that are relevant to you. This may include smoking cessation, regular exercise, treating high blood pressure, treating high cholesterol, and maintaining a healthy weight. If you are undergoing surgery, it is recommended that you speak to your surgeon about whether anticoagulant medication is required after surgery.

Conclusion

SERMs are a promising treatment option for transmasculine adolescents, as they can potentially inhibit some of the changes associated with puberty in people with ovaries, such as breast growth and menstruation. Raloxifene is the most widely used in gender affirming medical treatment, although tamoxifen has also been used in to reduce pubertal breast growth in adolescents. While research on SERMs in trans people is lacking, research on raloxifene and tamoxifen in cis adolescents indicate that they are reasonably safe and tolerated well.

Nonetheless, given our theoretical knowledge of the mechanisms of how SERMs work, it is important to note that may be limitations to how effective they are for puberty blockade. SERMs do not block oestrogen altogether, but influence the ways in which oestrogen acts on different tissues in the body. Hence, while SERMs may inhibit some of the changes associated with puberty in people with ovaries, such as breast growth and menstruation, they may stop the pubertal changes entirely.

References

  • Demir, K., Unuvar, T., Eren, S., Abaci, A., and Bober, E. (2010). “Tamoxifen as first-line treatment in a premenarchal girl with juvenile breast hypertrophy”. Journal of Pediatric and Adolescent Gynecology, 23 (5): e133-e136.
  • Hodax, J. K., and DiVall, S. (2023). “Gender-Affirming Endocrine Care for Youth With a Nonbinary Gender Identity”. Therapeutic Advances in Endocrinology and Metabolism, 14.
  • Lapid, O., van Wingerden, J. J., and Perlemuter, L. (2013). “Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review”. Journal of Pediatric Endocrinology and Metabolism, 26 (9-10): 803-807.
  • Lawrence, S. E., Faught, K. A., Vethamuthu, J., and Lawson, M. L. (2004). “Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia”. Journal of Pediatrics, 145 (1): 71-76.
  • Mirkin, S., Pickar, J. H. (2015). “Selective Estrogen Receptor Modulators (SERMs): A Review of Clinical Data”. Maturitas, 80: 52–57.
  • O’Hare, P. M., and Frieden, I. J. (2000). “Virginal breast hypertrophy”. Pediatric Dermatology, 17(4): 277–281.
  • Xu, J. Y., O’Connell, M. A., Notini, L., Cheung, A. S., Zwickl, S., and Pang, K. C. (2021). “Selective Estrogen Receptor Modulators: A Potential Option for Non-Binary Gender-Affirming Hormonal Care?” Frontiers in Endocrinology, 12: 701364.
  • Zehetner, A. (2015). “Tamoxifen to Treat Male Pubertal Gynaecomastia”. International Journal of Pediatric and Adolescent Medicine, 2: 152–156.
Updated on May 31, 2024

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