Metabolic safety of gender-affirming hormonal treatment in transgender females
Charalampos Milionis
A * , Konstantina Barouti A , Vassiliki Papadopoulou A , Foteini Pouliasi A , Efthymia Karlafti A , Sofia Makrydima A , Stavroula Karampa A , Evaggelia Venaki A and Eftychia Koukkou A
A
Abstract
Gender incongruence results from the mismatch between gender identity and thesex assigned at birth. The process of gender affirmation includes a series of procedures during which the transgender individual acquires phenotypic features of the desired sex. Hormonal therapy for transgender women aims to suppress endogenous androgens and replace them with estrogens. The present study sought to investigate the safety of feminizing therapy in transgender women in relation to somatometric and metabolic parameters.
The medical records of transgender women who received oral estradiol valerate and a gonadotropin-releasing hormone (GnRH) agonist for at least 18 months were reviewed. The study population had estradiol levels within the normal limits of the follicular phase of cisgender women of reproductive age and suppressed blood testosterone levels after 18 months of treatment. Changes in body mass index, glycemic and lipid profiles, hemoglobin and hematocrit, and liver function tests were examined. The paired t-test was used for statistical analysis.
The mean blood estradiol and testosterone levels after approximately 18 months of treatment were 85.65 pg/mL and 24 ng/dL, respectively. There was a statistically significant increase in blood triglycerides as well as a statistically significant decrease in hemoglobin and hematocrit. However, none of the participants developed severe hypertriglyceridemia or anemia. No significant changes were found in blood cholesterol (total, high-density lipoprotein, and low-density lipoprotein cholesterol), glucose, and liver enzymes.
Treatment with oral estradiol valerate and an intramuscular GnRH agonist is used in daily clinical practice to promote feminizing physical changes in transgender women. However, the possibility of side effects is not well documented. The present study demonstrated that achieving estradiol and testosterone levels within therapeutic targets is important for the safety of gender-affirming therapy.
Keywords: adverse effects, estradiol, estrogen replacement therapy, gender-affirming care, gender dysphoria, health services for transgender persons, metabolic diseases, transgender persons, triptorelin pamote.
References
1 T’Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of transgender medicine. Endocr Rev 2019; 40(1): 97-117.
| Crossref | Google Scholar | PubMed |
2 Boucher FJO, Chinnah TI. Gender dysphoria: a review investigating the relationship between genetic influences and brain development. Adolesc Health Med Ther 2020; 11: 89-99.
| Crossref | Google Scholar | PubMed |
3 Joseph A, Cliffe C, Hillyard M, Majeed A. Gender identity and the management of the transgender patient: a guide for non-specialists. J R Soc Med 2017; 110(4): 144-152.
| Crossref | Google Scholar | PubMed |
4 Goodman M, Adams N, Corneil T, Kreukels B, Motmans J, Coleman E. Size and distribution of transgender and gender nonconforming populations: a narrative review. Endocrinol Metab Clin North Am 2019; 48(2): 303-321.
| Crossref | Google Scholar | PubMed |
5 T’Sjoen G, Arcelus J, De Vries ALC, Fisher AD, Nieder TO, Özer M, Motmans J. European Society for Sexual Medicine position statement “Assessment and hormonal management in adolescent and adult trans people, with attention for sexual function and satisfaction”. J Sex Med 2020; 17(4): 570-584.
| Crossref | Google Scholar | PubMed |
6 Unger CA. Hormone therapy for transgender patients. Transl Androl Urol 2016; 5(6): 877-884.
| Crossref | Google Scholar | PubMed |
7 Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T’Sjoen GG. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2017; 102(11): 3869-3903.
| Crossref | Google Scholar | PubMed |
8 Madsen TE, Sobel T, Negash S, Shrout Allen T, Stefanick ML, Manson JE, Allison M. A review of hormone and non-hormonal therapy options for the treatment of menopause. Int J Womens Health 2023; 15: 825-836.
| Crossref | Google Scholar | PubMed |
9 Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab 2021; 35(6): 101551.
| Crossref | Google Scholar | PubMed |
10 Bouck EG, Grinsztejn E, Mcnamara M, Stavrou EX, Wolberg AS. Thromboembolic risk with gender-affirming hormone therapy: potential role of global coagulation and fibrinolysis assays. Res Pract Thromb Haemost 2023; 7(6): 102197.
| Crossref | Google Scholar | PubMed |
11 Masumori N, Nakatsuka M. Cardiovascular risk in transgender people with gender-affirming hormone treatment. Circ Rep 2023; 5(4): 105-113.
| Crossref | Google Scholar | PubMed |
12 Milionis C, Ilias I, Venaki E, Koukkou E. Glucose homeostasis, diabetes mellitus, and gender-affirming treatment. Biomedicines 2023; 11(3): 670.
| Crossref | Google Scholar | PubMed |
13 Xu M, Fralick D, Zheng JZ, Wang B, Tu XM, Feng C. The differences and similarities between two-sample t-test and paired t-test. Shanghai Arch Psychiatry 2017; 29(3): 184-188.
| Crossref | Google Scholar | PubMed |
14 Irving A, Lehault WB. Clinical pearls of gender-affirming hormone therapy in transgender patients. Ment Health Clin 2017; 7(4): 164-167.
| Crossref | Google Scholar | PubMed |
15 Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen MR, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020; 41(24): 2313-2330.
| Crossref | Google Scholar | PubMed |
16 Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: the role of antioxidant activity. Curr Atheroscler Rep 2012; 14(2): 101-107.
| Crossref | Google Scholar | PubMed |
17 Talayero BG, Sacks FM. The role of triglycerides in atherosclerosis. Curr Cardiol Rep 2011; 13(6): 544-552.
| Crossref | Google Scholar | PubMed |
18 Maraka S, Singh Ospina N, Rodriguez-Gutierrez R, Davidge-Pitts CJ, Nippoldt TB, Prokop LJ, Murad MH. Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab 2017; 102(11): 3914-3923.
| Crossref | Google Scholar | PubMed |
19 Cocchetti C, Castellini G, Iacuaniello D, Romani A, Maggi M, Vignozzi L, Schreiner T, den Heijer M, T’Sjoen G, Fisher AD. Does gender-affirming hormonal treatment affect 30-year cardiovascular risk in transgender persons? A two-year prospective European study (ENIGI). J Sex Med 2021; 18(4): 821-829.
| Crossref | Google Scholar | PubMed |
20 van Velzen DM, Paldino A, Klaver M, Nota NM, Defreyne J, Hovingh GK, Thijs A, Simsek S, T’Sjoen G, den Heijer M. Cardiometabolic effects of testosterone in transmen and estrogen plus cyproterone acetate in transwomen. J Clin Endocrinol Metab 2019; 104(6): 1937-1947.
| Crossref | Google Scholar | PubMed |
21 Bittner V. Estrogens, lipids and cardiovascular disease: no easy answers. J Am Coll Cardiol 2001; 37(2): 431-433.
| Crossref | Google Scholar | PubMed |
22 Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis following testosterone therapy. Sex Med Rev 2018; 6(1): 77-85.
| Crossref | Google Scholar | PubMed |
23 Defreyne J, Vantomme B, Van Caenegem E, Wierckx K, De Blok CJM, Klaver M, Nota NM, Van Dijk D, Wiepjes CM, Den Heijer M, T’Sjoen G. Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence. Andrology 2018; 6(3): 446-454.
| Crossref | Google Scholar | PubMed |
24 Antun A, Zhang Q, Bhasin S, Bradlyn A, Flanders WD, Getahun D, Lash TL, Nash R, Roblin D, Silverberg MJ, Tangpricha V, Vupputuri S, Goodman M. Longitudinal changes in hematologic parameters among transgender people receiving hormone therapy. J Endocr Soc 2020; 4(11): bvaa119.
| Crossref | Google Scholar | PubMed |
25 Zu Y, Yang J, Zhang C, Liu D. The pathological mechanisms of estrogen-induced cholestasis: current perspectives. Front Pharmacol 2021; 12: 761255.
| Crossref | Google Scholar | PubMed |
26 Shi L, Feng Y, Lin H, Ma R, Cai X. Role of estrogen in hepatocellular carcinoma: is inflammation the key? J Transl Med 2014; 12: 93.
| Crossref | Google Scholar | PubMed |
27 Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, Larson JC. Effect of estrogen therapy on gallbladder disease. JAMA 2005; 293(3): 330-339.
| Crossref | Google Scholar | PubMed |
28 Hashemi L, Zhang Q, Getahun D, Jasuja GK, McCracken C, Pisegna J, Roblin D, Silverberg MJ, Tangpricha V, Vupputuri S, Goodman M.. Longitudinal changes in liver enzyme levels among transgender people receiving gender affirming hormone therapy. J Sex Med 2021; 18(9): 1662-1675.
| Crossref | Google Scholar | PubMed |
29 Spanos C, Bretherton I, Zajac JD, Cheung AS. Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: a systematic review. World J Diabetes 2020; 11(3): 66-77.
| Crossref | Google Scholar | PubMed |
30 Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol 2013; 4: 863.
| Crossref | Google Scholar | PubMed |
