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.