Table 2.

Studies on the influence of testosterone therapy on hypogonadal symptoms, BMD, and metabolic and anthropometric parameters. First table shows results for hypogonadal men, and second table shows results for transgender men.

Author, year, (ref), study design	Intervention/comparator	Study population	Follow-up	Hypogonadal symptoms	Bone mineral density (BMD)	Metabolic and anthropometric parameters
Studies on men with hypogonadism
Aydogan 2012 (41), Prospective non-randomized study	Testosterone esters (TE) (Sustanon 250 mg every 3 weeks)/none	39 men with congenital hypogonadotropic hypogonadism vs 40 age-matched eugonadal men	6 months	Improvement of sexual function		Significant increase in BMI
Benito 2005 (84), Prospective study	Gel/none	10 untreated men with hypogonadism vs 10 eugonadal men	2 years		Increase in BMD
Bolu 2012 (60), Prospective study	TE/gel	70 men with hypogonadism vs 70 controls	6 months			After treatment, lower total cholesterol and lower high-density lipoprotein (HDL) cholesterol observed. BMI increased.
Cherrier 2003 (54), Prospective study	Gel (2 dosages)/patch	12 men with hypogonadism		Improvement in verbal memory after testosterone therapy (TT)
Chiang 2007 (42), Double-blind, randomized, placebo-controlled study	Gel/placebo	40 men with hypogonadism	3 months	Improvement of sexual function
Cunningham 2017 (26), Phase 3 open-label non-comparator study	Gel/none	160 men with hypogonadism	4 months	Improvement of sexual function, less fatigue
De Rosa 2001 (85), Cross-sectional study	TE/none	12 men with hypogonadism			Still decreased BMD after testosterone therapy
Efros 2016 (43), P hase II, open-label, sequential dose escalation studies	Gel, three different concentrations	38 men with hypogonadism	1 week	Improvement of sexual function. Less fatigue and distress
Kaufman 2011 (65), Multicenter, randomized, double-blind, placebo-controlled study	Gel/placebo	Men with hypogonadism gel were 214 and placebo 37	6 months			Increased BMI with TT
Khera 2011 (55), Prospective multicenter registry study	Gel/none	271 men with hypogonadism	1 year	Improvement of sexual function
Lasaite 2016 (44), Prospective study	TU/none	19 men with hypogonadism		Improvement in cognitive tests (trail making test, digit span test)
Leifke 1998 (87), Prospective study	TE/none	32 men with hypogonadism	3.2 ± 1.7 years		Increase in BMD
Malkin 2004 (66), Randomized, single-blind, placebo-controlled, crossover trial	TE/placebo	29 men with hypogonadism	1 month			Testosterone treatment gave reduction of total cholesterol and serum triglycerides
McNicholas 2003 (45), Randomized, multidose, multicenter, active-controlled study	Gel/patch	208 men with hypogonadism (68 Testim 50, 72 Testim 100, 68 Andropatch)	3 months	Improvement of sexual function	No changes in BMD	Increase in BMI, total cholesterol, decrease in HDL
Medras 2001 (89), Prospective, controlled study	TE/none	26 men with hypogonadism			No improvement in BMD
Miner 2013 (46), Registry study	Gel/ none	849 men with hypogonadism	1 year	Improvement of mood and depression
Minneman 2008 (67), Open-label, randomized, prospective clinical trial	TE/TU	40 men with hypogonadism	2.1 years			No difference in BMI. TU HDL lower compared to low density lipoprotein (LDL).
Mulhall 2004 (47), Prospective, observational study	Gel→ patch→ TE adjusted for testosterone levels	32 men with hypogonadism	1 year	Improvement of sexual function
Nieschlag 1999 (32), Open-label, clinical, non-randomized study	TU/none	13 men with hypogonadism	24 weeks	Improvement of sexual function compared to previous treatment (TE/gel)		Decrease in HDL, Stable BMI other lipids, glucose and HbA1c
O’Connor 2001 (48), Single-blind placebo-controlled study	TE/placebo	30 eugonadal and 7 men with hypogonadism		No improvement of cognitive tests in hypogonadal group (compared to eugonadal)
Ramasamy 2015 (49), Prospective, observational study	Gel/injections	42 men with hypogonadism	Median 3.8 years	No difference between gel and injections in hypogonadal symptoms
Schubert 2003 (90), Prospective, open-label randomized, trial	Mesterolone 100 mg/day/oral testosterone undecanoate 160 mg/day/testosterone enanthate depot 250 mg i.m./21 days, or testosterone pellets	53 men with hypogonadism	6 months		Increase in BMD in all groups
Seftel 2004 (56), Randomized, multidose, multicenter, active, placebo-controlled study	Gel (two different dosages)/patch/placebo	406 men with hypogonadism	2 years	Improvement in sexual desire and function
Sonmez 2015 (72), Prospective, controlled study	TE/Gel	60 men with hypogonadism vs 70 age-matched controls	6 months			Increase in systolic blood pressure, BMI and decrease in HDL cholesterol
Tahani 2018 (91), Prospective study	Gel/TU	15 men with hypogonadism with Klinefelter syndrome, 26 controls	3 years		Increase in BMD after testosterone treatment
Van den Berg 2001 (93), Cross-sectional study	TU/TE/oral	52 men with hypogonadism (Klinefelter)	1 year		44–48% had osteopenia, 6–14% osteoporosis. No fractures reported.
Von Eckardstein 2002 (39), Phase 2 study	TU/none	7 men with hypogonadism	2.8 years	Improvement of sexual function		Increase in BMI (due to increase in LBM), decrease in HDL, and total cholesterol
Wang 1996 (50), Prospective study	TE/sublingual	Men with hypogonadism 18 testosterone esters, 35 sublingual	2 months	Improvement in mood, decreased anger, and irritability sadness and tiredness
Wang 2001 (51), Prospective, randomized, multi-center, parallel clinical trial	Gel 50 or 100 mg	227 men with hypogonadism	6 months		Increase in BMD
Wang 2004 (78), Long-term, open-label efficacy study	Gel 50, 75, 100 mg	169 men with hypogonadism	3 years	Improvement of sexual function	Increase in BMD	BMI rose mostly due to an increase in lean body mass
Wolf 2017 (76), Observational post-marketing study	TU/ none	867 men with hypogonadism 3 transgender males	1 year			Stable BMI. Men with low blood pressure had an increase in blood pressure, men with high blood pressure had a decrease in blood pressure.
Wu 2009 (75), Prospective controlled study	3 months TU oral, after this monthy injections TU 250 mg	26 men with hypogonadism vs 26 healthy controls	9 months			Total cholesterol, LDL-C, HDL-C, and triglyceride were all decreased. No changes in body fat
Yassin 2013 (79), Cumulative registry study	TU/none	261 men with hypogonadism	5 years			Decrease in waist circumference and BMI after TT
Zitzmann 2013 (53), International, multicenter, one-arm, prospective, observational study in 23 countries	TU/ none	1438 men with hypogonadism	5 injections (1 year)	Improvement of concentration and sleep quality. Stability in mood, less hot flushes, and sweating.		Lower blood pressure and better lipid profile
Studies on transgender males
Elbers 2003 (43), Prospective study	TE/none	17 transgender males	1 year			Decrease in HDL cholesterol, increase in cholesterol, increase in BMI 1 year after TT
Emi 2008 (80), Prospective study	TE/ no treatment	63 untreated and 48 treated transgender males	-			Treated individuals had higher blood pressure, increased cholesterol, and decreased HDL cholesterol.
Gava 2021 (61), Randomized, double-blind PL-controlled pilot trial	Testosterone undecanoate (TU) + placebo/ TU + 5 α-reductase inhibitor	14 ovariectomized transgender males	1 year		No difference in BMD	Stable BMI, HDL decreased, fat% lower
Goh 1995 (62), Prospective study	TE/none	85 transgender males	33 months			Higher levels of triglyceride, total cholesterol, LDL and Apo-B, lower HDL
Haraldsen 2007 (95), Prospective study	TE/none	12 transgender males	1 year		No difference in BMD
Jacobeit 2007 (64), Prospective study	TU/none	12 transgender males	1 year			Stable BMI and lipid profile
Jacobeit 2009 (63), Prospective study	TU/none	17 transgender males	1.5 year			Stable lipid profile and BMI
Lips 1996 (88), Prospective study	TE (12)/oral (3)	15 transgender males	39 months		Normal BMD
Mueller 2007 (58), Prospective, observational study	TU/none	35 transgender males	1 year		No changes in BMD	Increased BMI, decreased HDL, other lipid parameters stable. Increase in systolic and diastolic blood pressure
Mueller 2010 (71), Prospective, observational study	TU/none	45 transgender males	2 years		No changes in BMD	Stable BMI but lean body mass (LBM) increased, decreased HDL, other lipid parameters stable
Pelusi 2014 (59), Observational study	Gel/Testoviron/TU	45 transgender males	1 year		No difference in BMD	BMI increased after starting testosterone therapy, independent of formulation. HDL decreased, LDL increased in all groups.
Turner 2004 (31), Prospective case series	TE/None	15 transgender males	2 years		Increase in BMD
Van Caenegem 2015 (92), Prospective, controlled study	TU/none	26 transgender males, 23 age-matched cis women	1 year		Small increase BMD
Van Velzen 2019 (74), Prospective, controlled study	TE or TU or Gel	188 transgender males 47 gel, 63 TE 79 TU	1 year			No differences in lipids, BMI, systolic and diastolic blood pressure, cholesterol HDL, LDL, and triglycerides for different formulations. Although BMI was higher in the group using TE.
Van Velzen 2020 (73), Prospective, controlled study	TE or TU or Gel	323 transgender males	2 years			Stable BMI but increase in LBM
Vlot 2019 (94), Prospective, controlled study	TE or TU or Gel	132 transgender males	1 year		Increase in BMD in younger transgender males, decrease in older transgender males
Wierckx 2014 (77), Prospective study	TE/TU	53 transgender males				Total body weight increased due to an increase in LBM. Systolic blood pressure increased