BACKGROUND: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. METHODS: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. FINDINGS: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. INTERPRETATION: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.
BACKGROUND: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. METHODS: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. FINDINGS: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. INTERPRETATION: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.
Authors: Nancy D Berkman; Kathleen N Lohr; Mohammed T Ansari; Ethan M Balk; Robert Kane; Marian McDonagh; Sally C Morton; Meera Viswanathan; Eric B Bass; Mary Butler; Gerald Gartlehner; Lisa Hartling; Melissa McPheeters; Laura C Morgan; James Reston; Priyanka Sista; Evelyn Whitlock; Stephanie Chang Journal: J Clin Epidemiol Date: 2014-12-20 Impact factor: 6.437
Authors: Nienke M Nota; Chantal M Wiepjes; Christel J M de Blok; Louis J G Gooren; Saskia M Peerdeman; Baudewijntje P C Kreukels; Martin den Heijer Journal: Brain Date: 2018-07-01 Impact factor: 13.501
Authors: N M Nota; M J H J Dekker; M Klaver; C M Wiepjes; M A van Trotsenburg; A C Heijboer; M den Heijer Journal: Andrologia Date: 2016-08-25 Impact factor: 2.775
Authors: Katrien Wierckx; Eva Van Caenegem; Thomas Schreiner; Ira Haraldsen; Alessandra D Fisher; Alessandra Fisher; Kaatje Toye; Jean Marc Kaufman; Guy T'Sjoen Journal: J Sex Med Date: 2014-05-14 Impact factor: 3.802
Authors: E Coleman; A E Radix; W P Bouman; G R Brown; A L C de Vries; M B Deutsch; R Ettner; L Fraser; M Goodman; J Green; A B Hancock; T W Johnson; D H Karasic; G A Knudson; S F Leibowitz; H F L Meyer-Bahlburg; S J Monstrey; J Motmans; L Nahata; T O Nieder; S L Reisner; C Richards; L S Schechter; V Tangpricha; A C Tishelman; M A A Van Trotsenburg; S Winter; K Ducheny; N J Adams; T M Adrián; L R Allen; D Azul; H Bagga; K Başar; D S Bathory; J J Belinky; D R Berg; J U Berli; R O Bluebond-Langner; M-B Bouman; M L Bowers; P J Brassard; J Byrne; L Capitán; C J Cargill; J M Carswell; S C Chang; G Chelvakumar; T Corneil; K B Dalke; G De Cuypere; E de Vries; M Den Heijer; A H Devor; C Dhejne; A D'Marco; E K Edmiston; L Edwards-Leeper; R Ehrbar; D Ehrensaft; J Eisfeld; E Elaut; L Erickson-Schroth; J L Feldman; A D Fisher; M M Garcia; L Gijs; S E Green; B P Hall; T L D Hardy; M S Irwig; L A Jacobs; A C Janssen; K Johnson; D T Klink; B P C Kreukels; L E Kuper; E J Kvach; M A Malouf; R Massey; T Mazur; C McLachlan; S D Morrison; S W Mosser; P M Neira; U Nygren; J M Oates; J Obedin-Maliver; G Pagkalos; J Patton; N Phanuphak; K Rachlin; T Reed; G N Rider; J Ristori; S Robbins-Cherry; S A Roberts; K A Rodriguez-Wallberg; S M Rosenthal; K Sabir; J D Safer; A I Scheim; L J Seal; T J Sehoole; K Spencer; C St Amand; T D Steensma; J F Strang; G B Taylor; K Tilleman; G G T'Sjoen; L N Vala; N M Van Mello; J F Veale; J A Vencill; B Vincent; L M Wesp; M A West; J Arcelus Journal: Int J Transgend Health Date: 2022-09-06