Abstract
Objective: In transsexual people, cross-sex hormone therapy is an important component of medical
treatment and results in a complete change in the sex hormone environment. Steroid
hormones plays an important role in developing and maintaining bone mass and body
composition in both sexes. The aim of this study was to evaluate changes in body composition
and bone mineral density (BMD) during cross-sex hormone therapy in transsexuals using
gonadotrophin-releasing hormone agonists and intramuscular oestrogens.
Methods: 84 male-to-female transsexuals (MtFs) were treated with 10 mg oestradiol-17β valerate
every 10 days. The study population was treated with subcutaneous injections of 3.8 mg
goserelin acetate every 4 weeks to suppress endogenous sex hormone secretion completely.
Endocrine parameters, body composition and BMD after 12 months and after 24 months
were compared with baseline values.
Results: There was a significant decline in gonadotrophins and testosterone, while oestradiol,
sex hormone-binding globulin, and high-density lipoprotein levels increased significantly
after 12 and 24 months. There was a significant increase in body mass index (BMI),
fat mass, and lumbar spine bone mineral density in MtFs during the study period, while
lean mass decreased significantly and no effect was observed on femoral bone mineral
density.
Conclusion: There was an increase in BMI associated with a shift from lean mass to fat mass.
There appears to be no risk of osteoporosis developing in MtFs when there is adequate
oestrogen substitution, even in the absence of testosterone. Furthermore in comparison
with hormone regimes using oral medications, the complication rates appear to be lower
in patients receiving gonadotrophin-releasing hormone agonists and intramuscular oestrogens.
Key words
transsexuals - cross-sex hormone treatment - body composition - bone mineral density
References
1
Aedo AR, Landgren BM, Diczfalusy E.
Pharmacokinetics and biotransformation of orally administered oestrone sulphate and
oestradiol valerate in postmenopausal women.
Maturitas.
1990;
12
333-343
2
Asscheman H, Gooren L, Assies J. et al .
Prolactin levels and pituitary enlargement in hormone-treated male to female transsexual
people.
Clin Endocrinol (Oxf).
1988;
28
583-588
3
Asscheman H, Gooren L, Eklund P.
Mortality and morbidity in transsexual patients with cross-gender hormone treatment.
Metabolism.
1989;
38
869-873
4
Brown MA, Haughton MA, Grant SF. et al .
Genetic control of bone density and turnover: role of the collagen 1alpha1, estrogen
receptor, and vitamin D receptor genes.
J Bone Miner Res.
2001;
16
758-764
5
Center JR, Nguyen TV, Sambrook PN. et al .
Hormonal and biochemical parameters in the determination of osteoporosis in elderly
men.
J Clin Endocrinol Metab.
1999;
84
3626-3635
6
Cupisti S, Dittrich R, Binder H. et al .
Influence of body mass index on calculated androgen parameters in adult women with
hirsutism and PCOS.
Exp Clin Endocrinol Diabetes.
2007;
115
380-386
7
Cupisti S, Kajaia N, Dittrich R. et al .
Body mass index and ovarian function are associated with endocrine and metabolic abnormalities
in women with hyperandrogenic syndrome.
Eur J Endocrinol.
2008;
158
711-719
8
Dittrich R, Binder H, Cupisti S. et al .
Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone
agonist.
Exp Clin Endocrinol Diabetes.
2005;
113
586-592
9
Elbers JM, Asscheman H, Seidell JC. et al .
Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance
imaging in transsexuals.
Am J Physiol.
1999;
276
E317-E325
10
Falch JA.
The effect of physical activity on the skeleton.
Scand J Soc Med Suppl.
1982;
29
55-58
11
Futterweit W.
Endocrine management of transsexual. Hormonal profiles of serum prolactin, testosterone,
and estradiol.
N Y State J Med.
1980;
80
1260-1264
12
Gooren L.
Hormone treatment of the adult transsexual patient.
Horm Res.
2005;
64
(S 02)
31-36
13
Gooren LJ.
Olympic sports and transsexuals.
Asian J Androl.
2008;
10
427-432
14
Gooren L, Assies J, Asscheman H. et al .
Estrogen-induced prolactinoma in a man.
J Clin Endocrinol Metab.
1988;
66
444-446
15
Gooren LJ, Giltay EJ, Bunck MC.
Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience.
J Clin Endocrinol Metab.
2008;
93
19-25
16
Greendale GA, Edelstein S, Barrett-Connor E.
Endogenous sex steroids and bone mineral density in older women and men: the Rancho
Bernardo Study.
J Bone Miner Res.
1997;
12
1833-1843
17
Guéguen R, Jouanny P, Guillemin F. et al .
Segregation analysis and variance components analysis of bone mineral density in healthy
families.
J Bone Miner Res.
1995;
10
2017-2022
18 Hamburger C. Endocrine treatment of male and female transsexualism. In: Green R,
Money J, (eds) Transsexualism and Sex Reassignment. Baltimore: Johns Hopkins Press;
1969: 291-307
19
Haraldsen IR, Haug E, Falch J. et al .
Cross-sex pattern of bone mineral density in early onset gender identity disorder.
Horm Behav.
2007;
52
334-433
20
Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA. et al .
Endocrine Society. Endocrine treatment of transsexual persons: an Endocrine Society
clinical practice guideline.
J Clin Endocrinol Metab.
2009;
94
3132-3154
21
Kajaia N, Binder H, Dittrich R. et al .
Low sex hormone-binding globulin as a predictive marker for insulin resistance in
women with hyperandrogenic syndrome.
Eur J Endocrinol.
2007;
157
499-507
22
Khosla S, Melton 3rd LJ, Atkinson EJ. et al .
Relationship of serum sex steroid levels and bone turnover markers with bone mineral
density in men and women: a key role for bioavailable estrogen.
J Clin Endocrinol Metab.
1998;
83
2266-2274
23
Kronawitter D, Gooren LJ, Zollver H. et al .
Effects of transdermal testosterone or oral dydrogesterone on hypoactive sexual desire
disorder in transsexual women: results of a pilot study.
Eur J Endocrinol.
2009;
161
363-368
24
Kuhl H.
Pharmacology of estradiol and estriol.
Menopause Rev.
2000;
5
23-44
25
Lapauw B, Taes Y, Simoens S. et al .
Body composition, volumetric and areal bone parameters in male-to-female transsexual
persons.
Bone.
2008;
43
1016-1021
26
Lewiecki EM.
Premenopausal bone health assessment.
Curr Rheumatol Rep.
2005;
7
46-52
27
Michel A, Mormont C, Legros J.
A psycho-endocrinological overview of transsexualism.
Eur J Endocrinol.
2001;
145
365-376
28
Moore E, Wisniewski A, Dobs A.
Endocrine treatment of transsexual people: a review of treatment regimens, outcomes,
and adverse effects.
J Clin Endocrinol Metab.
2003;
88
3467-3473
29
Mueller A, Dittrich R, Binder H. et al .
High dose estrogen treatment increases bone mineral density in male-to-female transsexuals
receiving gonadotropin-releasing hormone agonist in the absence of testosterone.
Eur J Endocrinol.
2005;
153
107-113
30
Mueller A, Binder H, Cupisti S. et al .
Effects on the male endocrine system of long-term treatment with gonadotropin-releasing
hormone agonists and estrogens in male-to-female transsexuals.
Horm Metab Res.
2006;
38
183-187
31
Mueller A, Kiesewetter F, Binder H. et al .
Long-term administration of testosterone undecanoate every 3 months for testosterone
supplementation in female-to-male transsexuals.
J Clin Endocrinol Metab.
2007;
92
3470-3475
32
Mueller A, Gooren LJ, Naton-Schötz S. et al .
Prevalence of polycystic ovary syndrome (PCOS) and hyperandrogenemia in female-to-male
transsexuals.
J Clin Endocrinol Metab.
2008;
93
1408-1411
33
Orwoll ES, Klein RF.
Osteoporosis in men.
Endocrine Rev.
1995;
16
87-117
34
Reutrakul S, Ongphiphadhanakul B, Piaseu N. et al .
The effects of oestrogen exposure on bone mass in male to female transsexuals.
Clin Endocrinol (Oxf).
1998;
49
811-814
35
Ruetsche AG, Kneubuehl R, Birkhaeuser MH. et al .
Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex
hormonal treatment: a cross-sectional study.
Osteoporos Int.
2005;
16
791-798
36
Schlatterer K, Auer DP, Yassouridis A. et al .
Transsexualism and osteoporosis.
Exp Clin Endocrinol Diabetes.
1998;
106
365-368
37
Slemenda CW, Longcope C, Zhou L. et al .
Sex steroids and bone mass in older men. Positive associations with serum estrogens
and negative associations with androgens.
J Clin Invest.
1997;
100
1755-1759
38
Stoch SA, Parker RA, Chen L. et al .
Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone
agonists.
J Clin Endocrinol Metab.
2001;
86
2787-2791
39
The World Professional Association for Transgender Health
.
http://www.wpath.org/publications_standards.cfm
40
T'sjoen G, Weyers S, Taes Y. et al .
Prevalence of low bone mass in relation to estrogen treatment and body composition
in male-to-female transsexual persons.
J Clin Densitom.
2009;
12
306-313
41
Vanderschueren D, Venken, Ophoff J.
et al
Sex steroids and the periosteum – reconsidering the roles of androgens and estrogens
in periosteal expansions.
J Clin Endocrinol Metab.
2006;
91
378-382
42
Van Kesteren P, Lips P, Deville W. et al .
The effect of 1-year cross-sex hormonal treatment on bone metabolism and serum insulin-like
growth factor-1 in transsexuals.
J Clin Endocrinol Metab.
1996;
81
2227-2232
43
Van Kesteren P, Asscheman H, Megens J. et al .
Mortality and morbidity in transsexual subjects treated with cross-sex hormones.
Clin Endocrinol (Oxf).
1997;
47
337-342
44
Van Kesteren P, Lips P, Gooren LJ. et al .
Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated
with cross-sex hormones.
Clin Endocrinol (Oxf).
1998;
48
347-354
Correspondence
Dr. A. Mueller
Department of Obstetrics and
Gynaecology
Erlangen University Hospital
Universitätsstraße 21–23
91054 Erlangen
Germany
Telefon: +49/9131/8533 553
Fax: +49/9131/8533 552
eMail: andreas.mueller@uk-erlangen.de