Pharmacological Reports 69 (2017) 432–437

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Pharmacological Reports
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Original article

The effect of L-thyroxine treatment on sexual function and depressive

symptoms in men with autoimmune hypothyroidism

Robert Krysiak* , Witold Szkróbka, Bogusław Okopien
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland

A R T I C L E I N F O A B S T R A C T

Article history: Background: Thyroid autoimmunity and mild hypothyroidism in women seem to be associated with
Received 19 November 2016 sexual dysfunction and depressive symptoms. Data concerning similar associations in men are limited.
Received in revised form 31 December 2016 The aim of this study was to investigate sexual functioning and depressive symptoms in men with
Accepted 11 January 2017
autoimmune hypothyroidism.
Available online 17 January 2017
Methods: The study population consisted of three groups: men with autoimmune overt hypothyroidism
(group A), men with autoimmune subclinical hypothyroidism (group B) and healthy euthyroid males
Keywords:
without thyroid autoimmunity (group C). Apart from measuring serum levels of thyrotropin and free
Depressive symptoms
Hypothyroidism
thyroid hormones and thyroid antibody titers, all included patients completed a questionnaires
Sexual functioning evaluating male sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the
Thyroid autoimmunity presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition BDI-II)
before and after 6 months of levothyroxine treatment.
Results: Men with overt hypothyroidism obtained lower scores in all five domains of IIEF-15, while men
with subclinical hypothyroidism only in erectile function. The total BDI-II score was higher in groups A
than in groups B and C, as well as higher in group B than in group C. L-thyroxine improved erectile
function and normalized intercourse satisfaction, orgasmic function, sexual desire and overall
satisfaction in group A, as well as normalized erectile function in group B. In group A, L-thyroxine
reduced, while in group B tended to reduce total BDI-II.
Conclusions: The obtained results suggest that autoimmune hypothyroidism in men is characterized by
sexual and mood disturbances and that hypothyroid patients with sexual dysfunction and depressive
symptoms benefit from L-thyroxine treatment.
© 2017 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.

Introduction
The prevalence and incidence of thyroid disorders is strongly
influenced by sex, being much higher in women than in men [1].
Despite female predominance, increasingly more and more men
are being diagnosed, particularly with hypothyroidism, which is by
far the most common thyroid disorder in the adult population and
in most men is autoimmune in origin [1,2].
Despite some discrepancies, results of few studies conducted to
date suggest that thyroid disorders may have an adverse effect on
male sexual functioning. Erectile dysfunction was more common in
men with thyroid disorders than in healthy controls, although its
Abbreviations: BDI-II, Beck Depression Inventory-Second Edition; IIEF-15,
International Index of Erectile Function-15; SD, standard deviation; TgAb,
thyroglobulin antibodies; TPOAb, thyroid peroxidase antibodies.
* Corresponding author.
E-mail address: r.krysiak@interia.pl (R. Krysiak).
frequency in this group of patients was lower than in men with
type 2 diabetes [3]. Both hyperthyroidism and hypothyroidism, if
untreated, were associated with impaired erectile function, which
improved after the restoration of normal hypothalamic-pituitary-
thyroid axis activity [4,5]. However, although the presence of overt
hyperthyroidism was associated with erectile dysfunction in the
study by Corona et al. [6], after adjusting for potential confounders
there as no association between erectile function and primary
hypothyroidism. In other studies [4,7], hypothyroidism and to a
lesser extent also hyperthyroidism reduced libido. Hypothyroidism
adversely affected sperm parameters, including sperm count,
morphology and motility [8]. Hyperthyroidism was found to be
associated with low total sperm count, lineal motility defects and
progressive motility abnormalities [9]. Moreover, hyperthyroidism
was found to be a common cause of acquired premature
ejaculation, while hypothyroidism was associated with delayed
ejaculation [4,10,11]. On the basis of these studies, we may
conclude that both thyroid hypofunction and hyperfunction affect
various aspects of male sexual functioning. However, conclusions

http://dx.doi.org/10.1016/j.pharep.2017.01.005
1734-1140/© 2017 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.
 R. Krysiak et al. / Pharmacological Reports 69 (2017) 432–437
from these studies are seriously limited by methodological
problems, particularly by a small number of men participating
in these studies, a retrospective nature of some studies, and
assessment of only selected aspects of men’s sexual response.
In our recent study, we have found that both thyroid
autoimmunity and hypothyroidism deteriorated female sexual
function and induced depressive symptoms and that their
deteriorating effects on sexuality in women were additive [12].
These results may suggest that sexual dysfunction and depressive
symptoms are more pronounced in women with thyroid hypo-
function induced by autoimmune thyroiditis than in women with
nonautoimmune hypothyroidism. Because similar data are not
available for males, the aim of the present study was to evaluate
sexual functioning and depressive symptoms in men with
autoimmune hypothyroidism of various severity before and after
L-thyroxine treatment.
Materials and methods
Patients
The participants of the study were recruited among adult men
(aged 18–50 years) with symptoms or signs suggestive of thyroid
dysfunction. Hashimoto’s thyroiditis was diagnosed if the patient
had positive thyroid peroxidase antibodies (TPOAb) (>100 U/mL)
and reduced echogenicity of the thyroid parenchyma on thyroid
ultrasonography. All sonographic examinations were performed by
the same person. Only patients unaware of their thyroid function
and not taking any drugs were included in the study. Based on
thyroid function test, the patients were enrolled into one of two
groups, each consisting of 12 individuals: patients with overt
hypothyroidism (plasma thyrotropin levels above 20 mU/L and free
thyroid hormone levels below the lower limit of the normal
laboratory range) (group A) and men with subclinical hypothy-
roidism (serum thyrotropin levels more than 4.5 mU/L but below
20 mU/L and normal free thyroid hormone levels) (group B). The
control group included 12 age- and weight-matched healthy men
without thyroid disease (Group C). These patients were character-
ized by serum thyrotropin levels between 0.45 and 4.5 mU/L, free
thyroid hormone levels and thyroid antibody titers within the
reference range and no abnormalities on thyroid ultrasound.
The exclusion criteria were as follows: hypogonadism, prolac-
tin-secreting tumors, diabetes, multiple sclerosis, prostatitis,
psychiatric problems, cardiovascular disease, impaired renal or
hepatic function, vasculogenic or neurogenic disorders known to
impair male sexual function, developmental or acquired anomalies
of the male reproductive system, as well as previous operations
that might have affected sexual function. The study protocol was
approved by our institutional review board and subjects gave
written, informed consent to participate in the study.
Study design
Patients with both overt and subclinical hypothyroidism were
then treated with L-thyroxine, which was administered at a
starting dose of 50 mg once-daily and gradually (over 4–8 weeks)
titrated to obtain thyrotropin levels in the range between 0.45 and
4.5 mU/L. The target daily dose of this agent was administered for
the following 6 months, and no changes in dosage were allowed
during this time.
Laboratory assays
Venous blood samples were drawn from the antecubital vein
between 8.00 and 9.00 a.m., at least 12 h after the last meal and
assessed in duplicate. Serum levels of thyrotropin, free thyroxine
433
and free triiodothyronine were measured with electrochemilumi-
nescence immunoassay reagents from Roche Diagnostics (Lewes,
United Kingdom). Serum levels of prolactin, as well as titers of
TPOAb and thyroglobulin antibodies (TgAb), were determined by
enzyme-linked immunosorbent assays using reagents purchased
from DRG Instruments GmbH (Marburg, Germany) and IBL
International (Hamburg, Germany). Intra- and interassay coef-
ficients of variation were less than 6.0 and 8.6%, respectively.
Thyroid ultrasound was performed with a 5- to 12-MHz linear
array transducer.
Questionnaires
The men were asked to complete a questionnaire assessing
their demographic characteristics, smoking, physical activity,
education, occupation, stress exposure, the number of sexual
partners, the number and duration of marriages, as well as systolic
and diastolic blood pressure. Sexual function and depressive
symptoms were assessed in all men considered for enrollment
immediately after blood collection and the ultrasound. However,
only data of the participants of the study were included in the final
analyses. Sexuality was evaluated using the International Index of
Sexual Function-15 (IIEF-15) for heterosexual men, consisting of
five collective sexual domains: erectile function, intercourse
satisfaction, orgasmic function, sexual desire and overall satisfac-
tion from sexual activity over the preceding 4 weeks. This self-
administered questionnaire, composed of 15 items, is regarded as a
reliable, cross-culturally valid, and psychometrically sound mea-
sure of male sexual function [13]. Each answer was rated on a scale
ranging from 0 to 5 or 1 to 5, with a higher score corresponding to
better sexual function. Total scores for each of the domains were
calculated separately by summing up individual question scores.
Erectile function was evaluated based on 6 questions (questions 1
to 5 and 15), yielding a maximum score of 30 points. An overall
erectile function below 26 indicated erectile dysfunction. Erectile
dysfunction was scored as follows: severe erectile dysfunction for
score no more than 10, moderate erectile dysfunction for score 11–
16, mild to moderate erectile dysfunction for score 17–21, and mild
erectile dysfunction for score 22–25. Intercourse satisfaction was
evaluated based on 3 questions (questions 6–8), yielding a
maximum score of 15 points. Orgasmic function (questions 9
and 10), sexual desire (questions 11 and 12) and overall satisfaction
(questions 13 and 14) were evaluated using two questions, yielding
a maximum score of 10 points. Minimum scores were: 0 for
intercourse satisfaction and orgasmic function, 1 for erectile
function, and 2 for sexual desire and overall satisfaction [14].
The presence of depression symptoms and depression severity
were evaluated using the Beck Depression Inventory-Second
Edition (BDI-II), which is a valid and reliable measure of depressive
state [15], corresponding well to a clinical diagnosis of depressive
disorders outlined in the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition [16]. Each item was rated on a 4-point
scale from 0 (not present) to 3 (severe) and the scores were added
to yield the total score, which can range from 0 to 63, with higher
values indicating more severe depressive symptoms. According to
manual guidelines [15], the total score of 0–13 was regarded as
minimal range, 14–19 as mild, 20–28 as moderate, and 29–63 as
severe depression.
Statistical analysis
Because of the skewed distributions, values for hormones and
thyroid antibodies were natural-log transformed to achieve
normality and homogeneity of variance. Comparisons between
the groups were performed using analysis of covariance followed
by Bonferroni post hoc tests after consideration of age, smoking,
434 R. Krysiak et al. / Pharmacological Reports 69 (2017) 432–437

Table 1
Sociodemographic characteristics of the study population.

Group A1 Group B2 Group C3

Number of patients 12 12 12
Age [years; mean (SD)] 38 (5) 35 (6) 34 (7)
Body mass index [kg/m2; mean (SD)] 30.2 (4.2) 28.5 (3.8) 28.2 (3.2)
Smokers [%]/Number of cigarettes a day [n; mean (SD)]/Duration of smoking [months, mean (SD)] 25/12 (6)/204 (84) 25/11 (5)/185 (86) 17/10 (4)/178 (65)
Physical activity: total/once a week/several times a week/once a month [%] 42/25/0/17a,b 75/25/25/25 84/42/25/17
Primary or vocational/secondary/university education [%] 16/42/42 8/50/42 8/42/50
Occupational activity/blue-collar/white-collar/pink-collar workers [%] 100/50/50/0 100/58/42/0 100/50/50/0
Number of sexual partners [n; mean (SD)] 3.0 (1.0) 2.8 (0.8) 2.6 (1.0)
Number of marriages [n; mean (SD)]/duration of marriages [months; mean (SD)] 1.3 (0.6)/128 (40) 1.2 (0.6)/118 (38) 1.2 (0.5)/110 (52)
Stress exposure [%, mean (SD)] 75 75 67
Systolic blood pressure [mm Hg; mean (SD)] 135 (12) 130 (10) 128 (8)
Diastolic blood pressure [mm Hg; mean (SD)] 84 (4) 82 (5) 81 (6)

SD – standard deviation. 1Men with overt hypothyroidism; 2men with subclinical hypothyroidism; 3healthy men with normal thyroid function. ap < 0.05 vs. group B; bp < 0.01
vs. group C.

body mass index, blood pressure, marital status, education, dysfunction were found in five (42%), two (17%) and three patients
occupational activity, type of work, profession, physical activity, (25%), respectively. In group B, three men (25%) had mild to
as well as stress exposure as potential confounders. Categorical moderate erectile dysfunction and two (16%) had mild erectile
variables were analyzed by x2 test. Pearson's r-tests were used to dysfunction. In group C, only one subject (8%) had mild erectile
test correlations and the degree of association among variables. dysfunction (data not shown).
Statistical significance was assumed less than 0.05. L-thyroxine administered to men belonging to group A
improved erectile function, reduced the percentage of men with
Results erectile dysfunction, as well as normalized intercourse satisfaction,
orgasmic function, sexual desire and overall satisfaction. In group
General characteristics of the study groups B, L-thyroxine normalized erectile function and reduced the
percentage of men with erectile dysfunction (Table 3). After
At study entry, all groups were comparable with respect to age, treatment with L-thyroxine, two patients (16%) belonging to group
smoking, education, occupational activity, a type of work, the A had mild while one (8%) had mild-to moderate erectile
number of sexual partners, the number and duration of marriages, dysfunction. Mild erectile dysfunction was found in two patients
stress exposure and blood pressure. There were differences (16%) from group B, as well as in one patient (8%) with normal
between the study groups in physical activity. Body mass index thyroid function. At the end of the study, patients from group A and
was insignificantly higher in men with overt hypothyroidism than C differed in erectile function.
in control subjects (p = 0.075) (Table 1). Expectedly, at the
beginning of the study, patients with overt hypothyroidism
exhibited higher serum levels of thyrotropin and prolactin, lower
serum levels of free thyroid hormones and higher titers of TPOAb
and TgAb than men with subclinical hypothyroidism and healthy Table 2
Serum hormone levels and antibody titers in the study population before and after
controls. Moreover, circulating levels of thyrotropin and prolactin,
L-thyroxine treatment.
as well as thyroid antibody titers were higher, while circulating
levels of free thyroid hormones lower in patients with subclinical Group A1 Group B2 Group C3
hypothyroidism than in control subjects (Table 2). Thyrotropin [mIU/L; mean (SD)]
No serious adverse effects were reported during the entire Baseline 42.8 (10.6)b,e 12.3 (4.0)e 1.6 (0.8)
At the end of the study 2.3 (0.8)h 2.1 (0.6)h 1.7 (0.8)
study period and all patients completed the study. The mean daily
dose of L-thyroxine was 130 mg in group A and 70 mg in group B. Free thyroxine [pmol/L; mean (SD)]
L-thyroxine administered to hypothyroid patients decreased serum Baseline 8.3 (1.2)b,e 13.2 (1.9)d 16.9 (2.9)
levels of thyrotropin and prolactin, increased serum levels of free At the end of the study 15.9 (2.3)h 16.2 (2.4)g 16.5 (2.5)
thyroxine and free triiodothyronine, as well as reduced TPOAb and
Free triiodothyronine [pmol/L; mean (SD)]
TgAb titers (Table 2). L-thyroxine did not affect body mass index
Baseline 2.8 (0.4)b,e 4.0 (0.4)d 5.0 (0.7)
and blood pressure (data not shown). No changes in the At the end of the study 5.1 (0.8)h 4.8 (0.5)g 4.9 (0.8)
investigated hormones and antibodies were observed in group
C, not receiving L-thyroxine treatment. Thyroid peroxidase antibodies [U/mL; mean (SD)]
Baseline 1680 (630)b,e 720 (280)e 25 (10)
At the end of the study 985 (352)b,e,g 435 (192)e,f 23 (11)
Sexual function
Thyroglobulin antibodies [U/mL; mean (SD)]
Men with overt hypothyroidism obtained lower scores in all five Baseline 1465 (532)b,e 685 (257)e 42 (15)
domains (erectile function, intercourse satisfaction, orgasmic At the end of the study 929 (381)b,e,f 426 (148)e,f 46 (18)
function, sexual desire and overall satisfaction), while men with
Prolactin [ng/mL; mean (SD)]
subclinical hypothyroidism only in one domain (erectile function). Baseline 25 (8)a,e 16 (5)c 10 (4)
Erectile function, intercourse satisfaction, orgasmic function, At the end of the study 10 (4)h 10 (5)f 8 (5)
sexual desire and overall satisfaction were more disturbed in SD – standard deviation. 1Men with overt hypothyroidism; 2men with subclinical
group A than in group B (Table 3). Moreover, the study groups hypothyroidism; 3healthy men with normal thyroid function. ap < 0.05, bp < 0.001
differed in the number of patients with erectile dysfunction and its vs. group B; cp < 0.05, dp < 0.01, ep < 0.001 vs. group C; fp < 0.05, gp < 0.01, hp < 0.001
severity. In group A, moderate, mild to moderate and mild erectile vs. baseline value.
 R. Krysiak et al. / Pharmacological Reports 69 (2017) 432–437 435

Table 3 Table 4
Sexual functions in men with autoimmune hypothyroidism. Depressive symptoms in men with autoimmune hypothyroidism.

Variable Group A1 Group B2 Group C3 Variable Group A1 Group B2 Group C3

Erectile function [mean (SD)] BDI-II score [mean (SD)]
Baseline 19.2 (5.1)a,e 24.4 (3.6)d 28.0 (1.5) Baseline 16.4 (3.6)b,e 12.6 (2.3)d 7.5 (3.2)
At the end of the study 25.9 (2.2)d,g 27.8 (1.7)f 28.2 (1.6) At the end of the study 12.0 (3.5)d,g 10.9 (3.0) 7.7 (3.6)

Erectile dysfunction [%] depressive symptoms [n (%)]

Baseline 83c,e 42d 8 Baseline 9 (75)a,e 5 (42)d 1 (8)
At the end of the study 25h 16f 8 At the end of the study 3 (25)g 3 (25) 1 (8)

Intercourse satisfaction [mean (SD)] mild symptoms [n (%)]

Baseline 8.8 (2.3)c,e 13.2 (1.5) 14.0 (1.3) Baseline 6 (50)d 5 (42)d 1 (8)
At the end of the study 13.5 (0.9)h 13.4 (1.2) 13.1 (0.6) At the end of the study 3 (25)f 3 (25) 1 (8)

Orgasmic function [mean (SD)] moderate symptoms [n (%)]

Baseline 6.8 (1.3)b,e 8.9 (1.1) 9.3 (0.8) Baseline 3 (25)a,c 0 (0) 0 (0)
At the end of the study 9.1 (0.7)h 9.3 (0.8) 9.2 (0.8) At the end of the study 0 (0)f 0 (0) 0 (0)

Sexual desire [mean (SD)] severe symptoms [n (%)]

Baseline 6.2 (1.5)b,e 8.1 (1.4) 9.0 (1.0) Baseline 0 (0) 0 (0) 0 (0)
At the end of the study 9.1 (0.8)h 8.6 (1.0) 9.0 (0.6) At the end of the study 0 (0) 0 (0) 0 (0)

SD – standard deviation. 1Men with overt hypothyroidism; 2men with subclinical

Sexual satisfaction [mean (SD)]
Baseline 6.0 (1.8)b,e 8.5 (1.1) 9.1 (1.3)
At the end of the study 9.3 (0.9)h 8.9 (0.8) 9.4 (0.6)
Overall satisfaction [mean (SD)]
Baseline 6.5 (2.0)a,e 8.6 (1.2) 9.3 (0.8)
At the end of the study 9.2 (0.7)h 8.8 (1.0) 9.2 (0.9)
SD – standard deviation. 1Men with overt hypothyroidism; 2men with subclinical
hypothyroidism; 3healthy men with normal thyroid function. ap < 0.05, bp < 0.01,
c
p < 0.001 vs. group B, dp < 0.05, ep < 0.001 vs. group C; fp < 0.05, gp < 0.01,
h
p < 0.001 vs. baseline value.
Depressive symptoms
The total BDI-II score was higher in patients with overt and
subclinical hypothyroidism than in men without thyroid disorders,
as well as higher in patients with overt than in patients with
subclinical hypothyroidism. Total, mild and moderate depressive
symptoms were reported most frequently in Group A, while the
presence of total and mild depressive symptoms in group B was
higher than in group C. In patients with overt hypothyroidism, L-
thyroxine treatment reduced the overall BDI-II score, as well as
decreased the percentage of patients with total, mild and moderate
depressive symptoms (Table 4). In men with subclinical hypothy-
roidism, L-thyroxine tended to reduce BDI-II score (p = 0.075), as
well as the number of patients with total (p = 0.065) and mild
(p = 0.065) depressive symptoms. The overall BDI-II score, as well
as the percentage of patients with total, mild, moderate and severe
depressive symptoms did not change throughout the study in
group C. At the end of the study, BDI-II score was higher in patients
with overt hypothyroidism and insignificantly higher (p = 0.057) in
men with subclinical hypothyroidism than in control subjects.
Correlations
At baseline, erectile function, intercourse satisfaction, orgasmic
function, sexual desire and overall satisfaction inversely correlated
with the total BDI-II score in all study groups, and with thyrotropin
levels in groups A and B (Table 5). In both groups of hypothyroid
men, erectile function inversely correlated with prolactin levels.
Moreover, in men with overt hypothyroidism, erectile function,
intercourse satisfaction, orgasmic function, sexual desire and
overall satisfaction, while in men with subclinical hypothyroidism
only erectile function positively correlated with free thyroid
hormone levels, and negatively with thyroid antibody titers. In
group A, the effect of the treatment on erectile function,
hypothyroidism; 3healthy men with normal thyroid function. ap < 0.05, bp < 0.01 vs.
group B; cp < 0.05, dp < 0.01, ep < 0.001 vs. group C; fp < 0.05, gp < 0.01 vs. baseline
value.
intercourse satisfaction, orgasmic function, sexual desire and
overall satisfaction correlated with treatment-induced changes in
thyrotropin, free thyroid hormones, antibody titers and the total
BDI-II score. In group B, there were correlations between the
improvement in erectile function and the effect of L-thyroxine on
thyrotropin, free thyroid hormone, antibody titers, and the total
BDI-II (Table 5). In groups A and B, treatment-induced changes in
erectile function correlated with a reduction in serum prolactin. No
other correlations were found.
Discussion
This study shows for the first time that autoimmune
hypothyroidism is associated with sexual dysfunction in men
and that the degree of this dysfunction depends both on the
severity of thyroid hypofunction and on the degree of thyroid
autoimmunity.
Impaired erection was the only sexual dysfunction observed in
men with subclinical hypothyroidism, as well as a domain the most
seriously affected in patients with overt hypothyroidism. Further-
more, correlations between hormone levels and thyroid antibody
titers were stronger for erection than for the remaining domains of
sexual functioning investigated in this study. All these findings
taken together suggest that erection may be disturbed at earlier
stages of thyroid hypofunction and/or inflammation, and may be
disturbed to a greater extent than other domains assessed in IIEF-
15. In light of these results, it seems reasonable to assume that men
with impotence of unknown origin should be assessed for the
presence of thyroid disease.
Vascular disease is the most common cause of impotence and
erectile dysfunction is an independent marker of cardiovascular
disease risk. Moreover, atherosclerosis and its complications may
partially contribute to disturbances in other aspects of male sexual
functioning [17,18]. Hypothyroidism, irrespective of the underlying
disorder is associated with hypercholesterolemia, arterial stiffness,
endothelial dysfunction and increased cardiovascular risk [19–22].
The presence of Hashimoto’s thyroiditis, even in euthyroid
subjects, was associated with a prothrombotic state, low-grade
systemic inflammation, enhanced lymphocyte and monocyte
release of proinflammatory cytokines, increased arterial stiffness
and increased thickness of the intima-media of the carotid arteries
436 R. Krysiak et al. / Pharmacological Reports 69 (2017) 432–437

Table 5
Correlation coefficients between the investigated parameters.

Correlated variables Group A1 Group B2 Group C3

c c c b
Erectile function Serum thyrotropin 0.49 (0.39) 0.43 (0.46) 0.12
Intercourse satisfaction Serum thyrotropin 0.40c (0.46)c 0.25a (0.22) 0.20
Orgasmic function Serum thyrotropin 0.34b (0.40)c 0.23a (0.14) 0.18
Sexual desire Serum thyrotropin 0.42c (0.50)c 0.26a (0.21) 0.22
Overall satisfaction Serum thyrotropin 0.43c (0.40)c 0.23a (0.20) 0.15
Erectile function Serum free thyroxine 0.38b (0.34)a 0.35b (0.26)a 0.23
Intercourse satisfaction Serum free thyroxine 0.30a (0.31)a 0.11 (0.12) 0.08
Orgasmic function Serum free thyroxine 0.28a (0.32)a 0.01 (0.13) 0.04
Sexual desire Serum free thyroxine 0.32a (0.28)a 0.15 (0.08) 0.19
Overall satisfaction Serum free thyroxine 0.35b (0.37)b 0.10 (0.18) 0.11
Erectile function Serum free triiodothyronine 0.39c (0.42)c 0.35b (0.29)a 0.11
Intercourse satisfaction Serum free triiodothyronine 0.29a (0.36)b 0.10 (0.13) 0.02
Orgasmic function Serum free triiodothyronine 0.23a (0.31)a 0.16 (0.05) 0.12
Sexual desire Serum free triiodothyronine 0.24a (0.35)b 0.12 (0.17) 0.04
Overall satisfaction Serum free triiodothyronine 0.30a (0.32)a 0.14 (0.13) 0.15
Erectile function TPOAb titers 0.42c (0.35)b 0.31a (0.37)b 0.12
Intercourse satisfaction TPOAb titers 0.32a (0.37)b 0.12 (0.14) 0.04
Orgasmic function TPOAb titers 0.28a (0.29)a 0.16 (0.19) 0.08
Sexual desire TPOAb titers 0.29a (0.31)a 0.10 (0.18) 0.01
Overall satisfaction TPOAb titers 0.30a (0.32)a 0.08 (0.10) 0.11
Erectile function TgAb titers 0.40c (0.29)a 0.35b (0.26)a 0.12
Intercourse satisfaction TgAb titers 0.34b (0.38)c 0.17 (0.12) 0.15
Orgasmic function TgAb titers 0.24a (0.30)a 0.18 (0.07) 0.11
Sexual desire TgAb titers 0.36b (0.35)b 0.14 (0.18) 0.17
Overall satisfaction TgAb titers 0.35b (0.34)b 0.15 (0.05) 0.16
Erectile function Serum prolactin 0.38b (0.30)a 0.28 (0.29)a 0.08
Intercourse satisfaction Serum prolactin 0.15 (0.10) 0.21 (0.08) 0.11
Orgasmic function Serum prolactin 0.18 (0.17) 0.15 (0.06) 0.12
Sexual desire Serum prolactin 0.10 (0.16) 0.15 (0.18) 0.15
Overall satisfaction Serum prolactin 0.13 (0.12) 0.15 (0.14) 0.04
Erectile function Total BDI-II score 0.43c (0.35)b 0.40c (0.37)b 0.46c
Intercourse satisfaction Total BDI-II score 0.49c (0.31)a 0.40c (0.18) 0.42c
Orgasmic function Total BDI-II score 0.50c (0.31)a 0.46c (0.18) 0.53c
Sexual desire Total BDI-II score 0.57c (0.48)c 0.50c (0.23) 0.48c
Overall satisfaction Total BDI-II score 0.38c (0.30)a 0.44c (0.14) 0.48c

Data represent the correlation coefficients (r values) at baseline and in parentheses between treatment-induced changes in the investigated parameters. 1Men with overt
hypothyroidism; 2men with subclinical hypothyroidism; 3healthy men with normal thyroid function. ap < 0.05, bp < 0.01, cp < 0.001. p values were adjusted for multiple
comparisons using the Bonferroni correction.

[23–26]. The autoimmune nature of hypothyroidism may partially
explain why all domains of sexual functioning were impaired in
men with overt hypothyroidism and why sexual dysfunction was
more pronounced in men with overt than in men with subclinical
hypothyroidism. In line with this explanation, a degree of sexual
dysfunction correlated both with hypothalamic-pituitary-thyroid
axis activity and thyroid antibody titers. Certainly, we cannot
exclude that the negative impact of autoimmune hypothyroidism
on male sexual functioning is mediated, at least in part, by its effect
on nerve function. This explanation is supported by previous
observations suggesting that thyroid hypofunction is associated
with both peripheral [27] and autonomic [28] polyneuropathy.
Another important finding resulting from our study was that
L-thyroxine normalized these domains of male sexual functioning,
the activity of which was impaired. Moreover, the strength of this
effect was proportional to a degree of treatment-induced changes
in thyroid antibody titers and in hypothalamic-pituitary axis
hypofunction. More prominent effect of L-thyroxine in group A may
be explained either by baseline differences in sexual activity
between both groups of hypothyroid patients and/or by using
higher doses of L-thyroxine in patients with overt hypothyroidism.
At the end of the study period, there were no statistical differences
between patients with subclinical hypothyroidism and control
subjects in erection function, as well as between groups A and B
and group C in other aspects of male sexual functioning, which
contrasted with clearly elevated antibody titers. This may mean
that some threshold degree of thyroid lymphocyte infiltration is
required to negatively affect male sexual functioning. Alternatively,
hypothalamic-pituitary-thyroid axis activity may be a more
important factor playing a role in proper sexual functioning that
thyroid autoimmunity.
Mean prolactin levels were higher in men with hypothyroidism
than in healthy controls, and were proportional to its severity. This
finding is in line with the presence of hyperprolactinemia in 40% of
patients with overt and 22% of patients with subclinical
hypothyroidism [29]. Interestingly, in both baseline conditions
and during treatment prolactin levels correlated exclusively with
erection. This finding seems interesting in the light of previous
studies, in which males with markedly elevated prolactin levels
secondary to pituitary adenoma were characterized by a greater
risk of hypoactive sexual desire [30]. A short-term increase in
prolactin levels is observed in healthy men following orgasm,
correlating with orgasm quality, and post-orgasmic prolactin
surges may serve as an neurohormonal index of sexual satiety
[31,32]. It cannot be excluded that persistently elevated levels of
this hormone may produce an inhibitory effect on subsequent
erection.
To the best of our knowledge, this study is the first to have
shown that the presence of Hashimoto’s thyroiditis is associated
with depression in males, as well as that the prevalence and
severity of depressive symptoms correlate with both antibody
titers and hypothalamic-pituitary-thyroid axis activity. Interest-
ingly, domain scores of IIEF-15 inversely correlated with the total
BDI-II score, as it was previously found in women [12]. The study
 R. Krysiak et al. / Pharmacological Reports 69 (2017) 432–437
protocol does not allow us to conclude whether depressive
symptoms in hypothyroid men with autoimmune thyroiditis
negatively affect sexual functioning or whether sexual dysfunction
plays a role in the development of depressive symptoms. Possible
mechanisms linking sexual dysfunction and depressive symptoms
include proinflammatory cytokines, a decrease in brain serotonin
content, as well as overactivity in the hypothalamic-pituitary-
adrenal axis. Although L-thyroxine produced a beneficial effect on
the BDI-II score, this effect was statistically significant only in men
with overt hypothyroidism. Moreover, at the end of the study the
overall BDI-II score, particularly in individuals with overt disease,
was still higher than in control subjects. These findings indicate
that the etiology of mood disturbances in men with autoimmune
hypothyroidism is multifactorial and that sexual dysfunction is
important, but not the only one, factor implicated in their
development and/or progression.
There are several limitations of the study that must be
acknowledged. Firstly, the study included a relatively small
number of men and was not randomized. Therefore, large
randomized clinical trials are needed to confirm our findings.
Secondly, although well-validated, the utility of FSFI and BDI-II
questionnaires, as other self-report inventories, is limited by their
subjectivity. Furthermore, the Upper Silesia, where the study was
performed, is a selenium-deficient area [33], with adequate iodine
intake (obligatory salt iodization) [34]. It is not certain whether
similar results were obtained in men living in selenium-sufficient
and/or iodine-deficient regions. Finally, L-thyroxine dose was
higher in patients with overt than subclinical thyroid dysfunction
and this fact may make it difficult to compare the effects of
treatment of both types of thyroid hypofunction.
In conclusion, overt hypothyroidism is associated with multi-
dimensional impairment of male sexual functioning, while sexual
dysfunction in men with subclinical hypothyroidism is limited to
impaired erection, which is accompanied by the presence of
depressive symptoms of various degree. L-Thyroxine treatment
reversed male sexual dysfunction and moderately reduced
depressive symptoms. The obtained results suggest that even
mild forms of autoimmune hypothyroidism in men are character-
ized by sexual and mood disturbances and that patients with their
presence benefit from L-thyroxine treatment.
Disclosure statement
The authors declare no conflicts of interest.
Institutional approval
The study was approved by the Bioethical Committee of the
Medical University of Silesia.
Funding
This work did not receive any funding.
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