Summary of evidence
Despite the limitations of the available studies, we clarified that
patients with hyperthyroidism have at least two-fold increased odds for
PE. Patients with hypothyroidism had more increased odds for DE compared
to hyperthyroidism subjects. Hyperthyroidism is much more common in
patients with PE; however, the latter association is not true for
lifelong PE sufferers who have normal erectile function. Current
evidence indicates that serum TSH levels in men are correlated with
their ejaculation latency control ability by means of time in both
hypothyroid and hyperthyroid subjects. From the treatment aspect,
relieving the thyroid disorder by itself improves both IELT control and
subjective PRO measures related to ejaculation at least 2 months after
the achievement of euthyroidism in men. Several aspects of erectile
function and the accompanying anxiety of the subjects also improved with
the treatment of thyroid disorders only.
With respect to the memory of Waldinger, who emphasized the necessity of
large cohorts (for example, to identify at least 55 lifelong PE
patients, you need at least 100,000 screened subjects) to demonstrate
the natural distribution of serum TSH among lifelong PE and non-PE
subjects, we are still far from clarifying the contribution of thyroid
hormone axis distortions to the ejaculatory reflex machinery with
currently available clinical studies (Waldinger et al., 2005). For
instance, if a case-control study aimed to reveal the proportions of
thyroid disorders among EjD sufferers, at least 833 subjects for each
group are needed to achieve 80% power with 95% CIs according to power
analysis for sample size with a known prevalence. Therefore, the lack of
large population-based comparative studies, excessive heterogeneity
across available studies, absence of standardization in the evaluation
of both objective (IELT) and subjective measures related to ejaculation,
erectile function, anxiety, etc., has led to a deficiency in the overall
completeness of our study evidence. The absence of placebo effect
elaboration and results of long-term follow-up studies with the presence
of selection bias also lowered the quantity of evidence for
interventional studies available in the current review.
The association of hyperthyroidism and PE with increased odds for each
other has been confirmed in our study, which is in agreement with
previous reports (Giovanni Corona, Jannini, Vignozzi, Rastrelli, &
Maggi, 2012a; Gabrielson et al., 2019). Considering that only one study
by Waldinger is available, the absence of this association among a
subgroup of patients who have lifelong PE has also been confirmed in our
study (Giovanni Corona, Jannini, Vignozzi, Rastrelli, & Maggi, 2012b;
Waldinger et al., 2005). On the other end of the ejaculatory axis, DE
has been shown to be strongly associated with hypothyroidism, which has
been reported in previous reviews, as evidenced by one available study
(Carani et al., 2005; Di Sante et al., 2016; Gabrielson et al., 2019).
Finally, the median age of the available studies that demonstrate the
aforementioned associations is in the forties, which agrees with the
previous argument that thyroid disorders may be a relevant risk factor
for sexual problems in young adults (Gabrielson et al., 2019).
The higher prevalence of anxiety among acquired PE patients and
hyperthyroid patients has been demonstrated with currently available
data (Cihan, Demir, et al., 2009; Culha, Tuken, Gonultas, Cakir, &
Serefoglu, 2020). However, the exact role of anxiety (direct or indirect
role) on the ejaculatory disturbance due to underlying thyroid
dysfunction is another issue that still remains to be clarified.
Treatment of thyroid dysfunction by itself has led to significant
improvements in the majority of patients with respect to ejaculatory
latency control, PRO measures related to ejaculation and accompanying
erectile function domains, and anxiety levels, which is demonstrated in
the available studies in our study and has already been reported in
previous reviews (Bates, Kohn, & Pastuszak, 2020; Sansone, Romanelli,
Jannini, & Lenzi, 2015). Surgically treated hyperthyroid patients
demonstrated much more improvement in their ejaculatory control outcomes
compared with other treatment groups, which should also be emphasized
again for planning future trials (Cihan, Demir, et al., 2009). However,
as shown by Bates et al., although there are statistically significant
and desired improvements in the IELT of subjects suffering from a
thyroid disorder, a small but perhaps clinically significant proportion
of patients still complain of EjD (Bates et al., 2020). Therefore, we
concluded that the relevance and different dimensions of treatment
effects with targeting euthyroidism alone on the EjD in patients with
thyroid disorder should be validated with large, longitudinal studies
with longer follow-up evaluations.