Usefulness of routine assessment of free testosterone for the diagnosis of functional male hypogonadism

Figures & data

Table 1. Comparison of clinical and biochemical data of patients presenting for symptoms of hypogonadism or infertility. 

	Patients with sexual symptoms (n = 188)	Patients with infertility (n = 184)	p
Age (years)	53.0 (40.0–61.0)	37.0 (33.0–41.0)	<.001
Weight (kg)	81.0 (75.0–92.0)	82.0 (74.0–91.5)	.926
BMI (kg/m²)	27.7 (24.2–30.0)	25.5 (23.4–28.5)	.017
Active smokers (%)	27 (23.9)	33 (28.2)	.059
Former smokers (%)	32 (28.3)	18 (15.4)
Erectile dysfunction (%)	160 (85.1)	8 (4.4)	<.001
Reduced morning erection (%)	91 (48.4)	3 (1.6)	<.001
Reduced libido (%)	65 (34.6)	2 (1.1)	<.001
Gynecomastia (%)	18 (9.6)	1 (0.5)	<.001
Diabetes mellitus type 2 (%)	36 (26.7)	3 (3.6)	<.001
Number of co-morbidities^a	2 (1–3)	1 (0–1)	<.001
TT (ng/ml)	4.3 (2.9–5.9)	4.5 (3.4–5.7)	.194
SHBG (nmol/L)	38.0 (27.8–49.0)	35.0 (25.4–45.0)	.047
cFT (pg/ml)	88.0 (66.0–106.8)	88.0 (71.0–110.0)	.580
Estradiol (pg/ml)	25.0 (25.0–31.0)	25.0 (25.0–31.0)	.416
LH (IU/L)	5.0 (3.2–7.6)	4.9 (3.4–6.5)	.573
FSH (IU/L)	4.8 (3.2–9.3)	5.7 (3.9–9.1)	.172
Haematocrit (%)	43.5 (40.2–46.1)	46.5 (45.2–48.8)	.051
PSA (ng/ml)	0.9 (0.6–1.5)	0.6 (0.4–0.9)	<.001
25-OH vitamin D (ng/ml)	20.0 (14.0–26.0)	20.0 (14.0–28.0)	.547

Data are expressed as median (interquartile range) for continuous variables and as absolute number (%) for categorical variables. Comparison for continuous variables was performed with Mann–Whitney’s test and for categorical variables with Pearson’s Chi-square Test.

Significant data are in bold.

BMI: body mass index; TT: total testosterone; SHBG: sex hormone binding globulin; cFT: calculated free testosterone; LH: luteinizing hormone; FSH: follicle stimulating hormone; PSA: prostate specific antigen.

^aCo-morbidities: osteoporosis, obesity, cardiovascular disease, diabetes mellitus type 2, liver diseases, kidney diseases.

Figure 1. Distribution of cases according to levels of TT and cFT. TT = total testosterone; cFT = calculated free testosterone. The patients are classified in six classes based on low, borderline, normal total testosterone concentrations and low or normal free testosterone concentrations.

Table 2. Type of hypogonadism based on LH and cFT.

	Patients with sexual symptoms (n = 174)	Patients with infertility (n = 184)	Total (n = 358)
Primary hypogonadism	12 (6.9%)	3 (1.6%)	15 (4.2%)
Normogonadotropic/ secondary hypogonadism	32 (18.4%)	18 (9.8%)	50 (14.0%)
Subclinical hypogonadism	17 (9.8%)	18 (9.8%)	35 (9.8%)
Eugonadism	113 (64.9%)	145 (78.8%)	258 (72.0%)

Primary hypogonadism: LH > 9.4 IU/L, cFT < 63 pg/mL; normogonadotropic/secondary hypogonadism: LH ≤ 9.4, cFT < 63 pg/mL; subclinical/compensated hypogonadism: LH > 9.4 IU/L and cFT ≥ 63 pg/L; eugonadism: LH ≤ 9.4, cFT ≥ 63 pg/L.

Table 3. Pearson’s correlations of TT/cFT with different variables.

	TT	p	cFT	p
Weight	−0.35	<.01	−0.17	<.01
BMI	−0.37	<.01	−0.24	<.01
Age	−0.08	.105	−0.29	<.01
HCT	0.13	.193	0.40	<.01
LH	0.01	.802	−0.16	<.01
FSH	−0.08	.129	−0.26	<.01
PSA	−0.03	.665	−0.06	.442
Decreased libido	−0.13	.090	−0.15	.070
Erectile dysfunction	−0.20	.688	−0.06	.288
Reduced morning erections	−0.20	.760	−0.04	.492
Gynecomastia	−0.06	.293	−0.12	.025
Number of co-morbidities	−0.19	<.01	−0.19	<.01

BMI: body mass index; TT: total testosterone; cFT: calculated free testosterone; LH: luteinizing hormone; FSH: follicle stimulating hormone; PSA: prostate specific antigen; HCT: haematocrit.

Significant data are in bold.

Table 4. Comparison between patients with low/normal cFT and with low/borderline/normal TT levels.

	TT (ng/ml)				cFT (pg/ml)
	<2.31 (n = 40)	2.31 < 3.50 (n = 77)	≥3.50 (n = 255)	p	<63 (n = 68)	≥63 (n = 304)	p
Age (years)	44.5 (31.5–57.5)	44.5 (36.0–57.0)	40.0 (34.0–52.0)	.328	51.5 (39.3–61.8)	40.0 (34.0–51.0)	<.01
Weight (kg)	88.0 (81.0–102.0)^a	88.0 (79.0–98.0)^a	80.0 (74.0–90.0)	<.01	87.0 (78.0–99.3)	81.0 (74.0–90.0)	<.01
BMI (kg/m²)	29.3 (26.9–31.5)^a	27.3 (24.3–30.1)	25.2 (23.5–27.8)	<.01	29.2 (26.0–30.0)	25.4 (23.5–28.2)	<.01
Number of co-morbidities^b	1 (0–2)	1 (0–3)^a	1 (0–2)	<.01	1 (1–3)	1 (0–2)	<.01
HCT (%)	43.5 (40.0–47.0)	43.6 (40.0–47.7)	44.0 (40.8–46.2)	.931	41.9 (40.0–44.5)	44.8 (40.9–47.2)	.032
PSA (ng/ml)	0.7 (0.4–1.0)	0.7 (0.4–1.4)	0.8 (0.6–1.3)	.255	0.7 (0.5–1.1)	0.8 (0.5–1.3)	.258
25-OH vitamin D (ng/ml)	21.5 (13.3–28.8)	18.5 (14.0–26.3)	20.0 (14.0–27.0)	.641	20.0 (14.0–29.0)	20.0 (14.0–26.0)	.609
Reduced morning erections	13/40 (32.5%)	20/77 (26.0%)	61/255 (23.9%)	.488	18/68 (26.5%)	76/304 (25.0%)	.801
Erectile dysfunction	23/40 (57.5%)	38/77 (49.4%)	107/255 (42.0%)	.114	39/68 (57.4%)	129/304 (42.4%)	.025
Decreased libido	11/40 (27.5%)^a	22/77 (28.6%)^a	34/255 (13.3%)	<.01	18/68 (26.5%)	49/304 (16.1%)	.045
Gynecomastia	3/40 (7.5%)	5/77 (6.5%)	11/255 (4.3%)	.56	6/68 (8.8%)	13/304 (4.3%)	.124

Data are expressed as median (interquartile range) for continuous variables and as absolute number (%) for categorical variables. Comparison for continuous variables was performed with Mann–Whitney’s/Kruskal–Wallis’s test as appropriated and for categorical variables with Pearson’s Chi-square Test.

Significant data are in bold.

BMI: body mass index; TT: total testosterone; cFT: calculated free testosterone; PSA: prostate specific antigen; HCT: haematocrit.

^aSignificantly different from men with TT ≥3.50 ng/ml.

^bCo-morbidities: osteoporosis, obesity, cardiovascular disease, diabetes mellitus type 2, liver diseases, kidney diseases.

Table 5. Binary linear logistic regression on the factors associated with low testosterone. Singificant data are in bold.

	TT < 2.31 ng/ml			TT < 3.50 ng/ml			cFT < 63 pg/ml
	OR	CI	p	OR	CI	p	OR	CI	p
Age	1.04	0.97–1.12	.228	1.03	0.98–1.07	.271	1.08	1.02–1.15	.016
Erectile dysfunction	0.39	0.04–3.86	.418	1.40	0.31–6.29	.658	0.49	0.07–3.40	.472
Reduced morning erections	2.20	0.21–22.80	.510	0.52	0.10–2.62	.427	0.12	0.01–1.43	.093
Decreased libido	4.32	0.49–37.80	.186	1.79	0.31–10.38	.518	10.27	0.90–116.94	.061
Gynecomastia	1.87	0.24–14.39	.548	1.83	0.39–8.54	.442	2.68	0.36–18.79	.349
BMI	1.35	1.13–1.61	.001	1.32	1.15–1.52	<.01	1.21	1.04–1.41	.014
Number of co-morbidities	0.44	0.18–1.08	.073	0.48	0.26–0.86	.015	0.90	0.50–1.60	.714

OR: Odds ratio; CI: confidence intervals; BMI: body mass index; TT: total testosterone; cFT: calculated free testosterone.

Significant data are in bold.

Figure 2. ROC curve of cFT and TT values predictive of sexual symptoms. Analysis of the accuracy of free testosterone and total testosterone in the diagnosis of sexual symptoms.