Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism

Çelik, Mehmet; Özçelik, Serhat; Baş, Süleyman; Sariaydin, Mehmet; Özçelik, Melike; Gozu, Hulya

doi:10.20945/2359-3997000000399

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Original Article • Arch. Endocrinol. Metab. 65 (5) • 2021 • https://doi.org/10.20945/2359-3997000000399 copy

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism.

Materials and methods:

Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed.

Results:

The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05).

Conclusion:

In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

Keywords
Hypogonadism; testosterone to estradiol ratio; morning erection

Variable		Value (n: 36)
Age (year) ^* * Data are presented as mean ± standard deviation (SD).		28.5 ± 8.7
BMI (kg/m²) ^* * Data are presented as mean ± standard deviation (SD).		25.5 ± 2.7
Hematocrit (%) ^* * Data are presented as mean ± standard deviation (SD).		44.0 ± 3.4
FSH (mIU/mL) ^† † Data are presented as median (interquartile range [IQR]).		1.6 [2.9]
LH (mIU/mL) ^† † Data are presented as median (interquartile range [IQR]).		0.9 [1.7]
ACTH (pg/mL) ^* * Data are presented as mean ± standard deviation (SD).		23.9 ± 7.2
Cortisol (μg/dL) ^† † Data are presented as median (interquartile range [IQR]).		11.6 [6.2]
TSH (μIU/mL) ^† † Data are presented as median (interquartile range [IQR]).		1.8 [1.3]
Prolactin (ng/mL) ^* * Data are presented as mean ± standard deviation (SD).		9.8 ± 5.5
Mean testicular volume (mL) (hCG treatment) (n: 17) ^† † Data are presented as median (interquartile range [IQR]).	Left	1.6 [1.9]
	Right	1.6 [2.5]
Mean testicular volume (mL) (T treatment) (n: 19) ^† † Data are presented as median (interquartile range [IQR]).	Left	1.1 [6.3]
	Right	1.0 [5.8]
Total testosterone (ng/mL) ^† † Data are presented as median (interquartile range [IQR]).		50.5 [51]
Estradiol (pg/mL) ^* * Data are presented as mean ± standard deviation (SD).		32.0 ±12

Age (Years) ^* * Data are presented as mean ± Standard deviation (SD).	26.88 ± 6.75	29.95 ± 10.03	0.296 ^a a Independent sample t-test.
BMI (kg/m²) ^* * Data are presented as mean ± Standard deviation (SD).	25.53 ± 2.62	25.58 ±2.83	0.953 ^a a Independent sample t-test.
Hematocrit (%) ^* * Data are presented as mean ± Standard deviation (SD).	45.40 ± 3.14	42.91 ± 3.35	0.029 ^a a Independent sample t-test.
Total cholesterol (mg/dL)	167.9 ± 27.6	152.1 ± 26.8	0.103 ^a a Independent sample t-test.
HDL-cholesterol (mg/dL)	49.8 ± 10.3	42.8 ± 13.4	0.254 ^a a Independent sample t-test.
LDL-cholesterol (mg/dL)	93.3 ± 21.3	88.7 ± 22.3	0.328 ^a a Independent sample t-test.
Triglyceride (mg/dL)	121.6 ± 67.8	100.2 ± 54.3	0.356 ^a a Independent sample t-test.
FSH (mIU/mL) ^† † Data are presented as median (interquartile range [IQR]).	1.3 [2.0]	2.4 [8.8]	0.030 ^b b Mann-Whitney test.
LH (mIU/mL) ^† † Data are presented as median (interquartile range [IQR]).	0.6 [1.6]	1.8 [6.8]	0.129 ^b b Mann-Whitney test.
ACTH (pg/mL) ^* * Data are presented as mean ± Standard deviation (SD).	28.90 ± 17.81	23.22 ± 10.49	0.246 ^a a Independent sample t-test.
Cortisol (μg/dL) ^† † Data are presented as median (interquartile range [IQR]).	13.8 [7.7]	10.6 [9.0]	0.076 ^b b Mann-Whitney test.
TSH (μIU/mL) ^† † Data are presented as median (interquartile range [IQR]).	1.8 [1.1]	1.6 [1.4]	0.186 ^b b Mann-Whitney test.
Prolactin (ng/mL) ^* * Data are presented as mean ± Standard deviation (SD).	9.10 ± 4.18	10.34 ± 6.51	0.508 ^a a Independent sample t-test.
Mean left testicular volume (mL) ^† † Data are presented as median (interquartile range [IQR]).	1.1 [6.3]	1.6 [1.9]	0.510 ^b b Mann-Whitney test.
Mean right testicular volume (mL) ^† † Data are presented as median (interquartile range [IQR]).	1.0 [5.8]	1.6 [2.5]	0.415 ^b b Mann-Whitney test.
Total testosterone (ng/mL) ^† † Data are presented as median (interquartile range [IQR]).	36 [31]	60 [86]	0.112 ^b b Mann-Whitney test.
Estradiol (pg/mL) ^* * Data are presented as mean ± Standard deviation (SD).	20.6 ± 2.5	29.9 ± 2.2	0.251 ^a a Independent sample t-test.

	Before Treatment	1^st Month	3^rd Month	6^th Month
T level in those receiving hCG therapy (ng/dL)	36	220	319	384
Average dose of hCG therapy (IU/week)	-	4,558	6,500	7,264

	Before testosterone treatment (n: 19)	After testosterone treatment (n: 19)	p	Before hCG treatment (n: 17)	After hCG treatment (n: 17)	p
Total testosterone (ng/dL) ^† † Data are presented as median (interquartile range [IQR]).	60 [86]	400 [234]	<0.001 ^a a Wilcoxon signed ranks test.	36 [31]	384 [220]	<0.001 ^a a Wilcoxon signed ranks test.
Estradiol (pg/mL) ^* * Data are presented as mean ± standard deviation (SD).	29.9 ± 2.2	29.5 ± 2.4	0.149 ^b b Paired samples t-test.	20.6 ± 2.5	40.8 ± 1.9	<0.001 ^b b Paired samples t-test.
Total testosterone to estradiol ratio ([ng/dL]/[pg/mL]) ^† † Data are presented as median (interquartile range [IQR]).	1.8 [2.9]	13.3 [9]	<0.00 ^a a Wilcoxon signed ranks test.	1.6 [1.5]	9.1 [6]	<0.00 ^a a Wilcoxon signed ranks test.
Morning erections (≥3/week), (n, %)	0 (0%)	10 (58.8%)	0.002 ^a a Wilcoxon signed ranks test.	0 (0%)	6 (35.3%)	0.014 ^a a Wilcoxon signed ranks test.
Right Mean testicular volume (mL) ^† † Data are presented as median (interquartile range [IQR]).	1.6 [2.5]	1.8 [2.2]	0.110 ^a a Wilcoxon signed ranks test.	1.0 [5.8]	2.5 [6.5]	<0.001 ^a a Wilcoxon signed ranks test.
Left Mean testicular volume (mL) ^† † Data are presented as median (interquartile range [IQR]).	1.6 [1.9]	1.8 [3.4]	0.008 ^a a Wilcoxon signed ranks test.	1.1 [6.3]	2.8 [7.5]	<0.001 ^a a Wilcoxon signed ranks test.
Lumbar Z score ^† † Data are presented as median (interquartile range [IQR]).	-2.9 [1.2]	-2.2 [0.9]	<0.001 ^a a Wilcoxon signed ranks test.	-2.7 [1.5]	-2.1 [0.7]	<0.001 ^a a Wilcoxon signed ranks test.

	Testosterone treatment (n: 19)	hCG treatment (n: 17)	P
Δ Total testosterone (ng/dL) ^† † Data are presented as mean ± Standard deviation (SD).	345.7 ± 136.0	400.5 ± 151.7	0.264 ^b b Independent t-test.
Δ Estradiol (pg/mL) ^* * Data are presented as median (interquartile range [IQR]).	-1 [2]	20 [2]	<0.001 ^a a Mann-Whitney U test.
Morning erections (≥3/week), (n, %) ^* * Data are presented as median (interquartile range [IQR]).	10 [52.6%]	6 [35.3%]	0.478 ^c c Yates (Continuity Correction) χ 2 test.
Δ Total testosterone to estradiol ratio ^† † Data are presented as mean ± Standard deviation (SD).	9.4 ± 5.8	8.9 ± 4.4	0.063 ^b b Independent t-test.
Δ Left Mean testicular volume (mL) ^* * Data are presented as median (interquartile range [IQR]).	0 [0.3]	1.2 [1.5]	<0.001 ^a a Mann-Whitney U test.
Δ Right Mean testicular volume (mL) ^* * Data are presented as median (interquartile range [IQR]).	0 [0.4]	1.3 [1.5]	<0.001 ^a a Mann-Whitney U test.

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[1] Correspondence to: Serhat Özçelik, Department of Endocrinology and Metabolism, Adiyaman Training and Research Hospital Adiyaman, Turkey. ozserhat1981@gmail.com