Notes on the Journey

Letter to the Editor: “Endocrine Treatment of
Gender-Dysphoric/Gender-Incongruent Persons:
An Endocrine Society Clinical Practice Guideline”

Michael K. Laidlaw,1 Quentin L. Van Meter,2 Paul W. Hruz,3 Andre Van Mol,4
and William J. Malone5
Michael K. Laidlaw, MD, Inc., Rocklin, California 95677; 2
Van Meter Pediatric Endocrinology, P.C., Atlanta,
Georgia 30318; 3
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
63110; 4
Van Mol Family Practice, Redding, California 96003; and 5
William J. Malone, MD, Twin Falls, Idaho
ORCiD numbers: 0000-0001-6849-7285 (M. K. Laidlaw); 0000-0003-2831-6480 (Q. L. Van Meter);
0000-0002-1478-3355 (P. W. Hruz); 0000-0001-8678-0025 (A. Van Mol);
0000-0002-5150-292X (W. J. Malone).

transgenderChildhood gender dysphoria (GD) is not an endocrine
condition, but it becomes one through iatrogenic
puberty blockade (PB) and high-dose cross-sex (HDCS)
hormones. The consequences of this gender-affirmative
therapy (GAT) are not trivial and include potential sterility,
sexual dysfunction, thromboembolic and cardiovascular
disease, and malignancy (1, 2).
There are no laboratory, imaging, or other objective tests to
diagnose a “true transgender” child. Children with GD will
outgrow this condition in 61% to 98% of cases by adulthood
(3). There is currently no way to predict who will desist and
who will remain dysphoric. The degree to which GAT has
contributed to the rapidly increasing prevalence of GD in
children is unknown. The recent phenomenon of teenage girls
suddenly developing GD (rapid onset GD) without prior
history through social contagion is particularly concerning (4).
GnRH agonists are used in precocious puberty to delay
the abnormally early onset of puberty to a physiologically
normal age. The goal of PB in the healthy child, however,
is to induce hypogonadotropic hypogonadism to “buy
time” to confirm gender incongruence. In a study of PB in
adolescents aged 11 to 17 years, 100% desired to continue
GAT. They simply “bought” themselves lower bone density
and the need for lifelong medical therapy (5).
Studies show that ,5% of adolescents receiving GAT
even attempt fertility preservation (6). Those started on PB at
Tanner stage II, as recommended by current guidelines, will
be blocked prior to sperm maturation and ovum release.
They will have no prospect of biological offspring while
on HDCS hormones and continuing on to gonadectomy.
The Endocrine Society’s guidelines recommend elevating females’ testosterone levels from a normal of 10 to
50 ng/dL to 300 to 1000 ng/dL, values typically found
with androgen-secreting tumors. The ovaries of women
given testosterone correspond to those found in PCOS,
which itself is associated with increased ovarian cancer
risk and metabolic abnormalities (1). Venous thromboembolism risk is elevated fivefold in males taking estrogen (2).
The health consequences of GAT are highly detrimental, the stated quality of evidence in the guidelines
is low, and diagnostic certainty is poor. Furthermore,
limited long-term outcome data fail to demonstrate longterm success in suicide prevention (7). How can a child,
adolescent, or even parent provide genuine consent to
such a treatment? How can the physician ethically administer GAT knowing that a significant number of
patients will be irreversibly harmed?
Hypothesis-driven randomized controlled clinical
trials are needed to establish and validate the safety and
efficacy of alternate treatment approaches for this vulnerable patient population. Existing care models based on psychological therapy have been shown to alleviate GD in
children, thus avoiding the radical changes and health
risks of GAT (8). This is an obvious and preferred therapy,
as it does the least harm with the most benefit.
In our opinion, physicians need to start examining
GAT through the objective eye of the scientist-clinician
rather than the ideological lens of the social activist. Far
more children with gender dysphoria will ultimately be
helped by this approach.

ISSN Print 0021-972X ISSN Online 1945-7197
Printed in USA
Copyright © 2019 Endocrine Society
Received 5 September 2018. Accepted 20 November 2018.
First Published Online 23 November 2018
686 J Clin Endocrinol Metab, March 2019, 104(3):686–687 doi: 10.1210/jc.2018-01925
Downloaded from by Washington University, Law School Library user on 23 January 2019
Disclosure Summary: Q.L.V.M. is a speaker for Abbvie and is
involved in clinical research with Abbvie on Depot Lupron. The
remaining authors have nothing to disclose.
1. 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.
2. Irwig MS. Cardiovascular health in transgender people. Rev Endocr
Metab Disord. 2018;19(3):243–251.
3. Ristori J, Steensma TD. Gender dysphoria in childhood. Int
Rev Psychiatry. 2016;28(1):13–20.
4. Littman L. Rapid-onset gender dysphoria in adolescents and young
adults: a study of parental reports. PLoS One. 2018;13(8):
5. de Vries ALC, Steensma TD, Doreleijers TAH, Cohen-Kettenis PT.
Puberty suppression in adolescents with gender identity disorder: a
prospective follow-up study. J Sex Med. 2011;8(8):2276–2283.
6. Nahata L, Tishelman AC, Caltabellotta NM, Quinn GP. Low
fertility preservation utilization among transgender youth.
J Adolesc Health. 2017;61(1):40–44.
7. Dhejne C, Lichtenstein P, Boman M, Johansson AL, Langstr ¨ ˚ om
N, Land´en M. Long-term follow-up of transsexual persons
undergoing sex reassignment surgery: cohort study in Sweden.
PLoS One. 2011;6(2):e16885.
8. Zucker KJ, Wood H, Singh D, Bradley SJA. A developmental,
biopsychosocial model for the treatment of children with gender
identity disorder. J Homosex. 2012;59(3):369–397.

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