madman
Super Moderator
Abstract
The aim of this review is to provide relevant information regarding the impact of thyroid disease, starting from birth and mainly concerning hyperthyroidism and hypothyroidism, on reproduction. Hyperthyroidism occurs much less commonly in children than hypothyroidism, with Graves’ disease (GD) being the most common cause of thyrotoxicosis in children. Children born with neonatal GD have no defects in the reproductive system that could be related to hyperthyroidism. Current treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine (RAI). In males, normal thyroid function seems important, at least in some parameters, for maintenance of semen quality via genomic or non-genomic mechanisms, either by locally acting on Sertoli cells, Leydig cells, or germ cells, or by affecting crosstalk between the HPT axis and the HPG axis. Sexual behavior may also be affected in thyroxic men, although many of these patients may have normal free testosterone levels. In women, menstrual irregularities are the most common reproduction-related symptoms in thyrotoxicosis, while this disorder is also associated with reduced fertility, although most women remain ovulatory. An increase in sex hormone-binding globulin (SHBG) and androgens, thyroid autoimmunity, and an impact on uterine oxidative stress are the main pathophysiological mechanisms which may influence female fertility. Thyroid hormones are responsible for normal growth and development during pre- and postnatal life, congenital hypothyroidism (CH) being the most common cause of neonatal thyroid disorders, affecting about one newborn infant in 3500. The reproductive tract appears to develop normally in cretins. Today, CH-screening programs allow for early identification and treatment, and, as a result, affected children now achieve normal or near-normal development. Hypothyroidism in males is associated with decreased libido or impotence. Although little is currently known about the effects of hypothyroidism on spermatogenesis and fertility, it has been established that sperm morphology and motility are mainly affected. In women of reproductive age, hypothyroidism results in changes in cycle length and amount of bleeding. Moreover, a negative effect on fertility and higher miscarriage rates has also been described.
Thyrotoxicosis in males and reproduction
Hormonal changes
Thyroid hormone regulates the synthesis of two sex hormone binding (SHB) proteins [8], namely, sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, and androgen-binding protein(ABP), synthesized by the Sertoli cell [9]. ABP maintains the necessary levels of intratesticular androgen for germ cell maturation and differentiation. In rats and in humans, SHBG and ABP have the same amino acid sequence, as they are encoded by the same SHBG gene, though they differ in carbohydrate content and structure (glycosylation) [9–11].
An increase in SHBG has been a feature consistently associated with thyrotoxicosis, which state leads to increased circulating levels of total testosterone (T) and a reduction in the metabolic clearance rate of T [12, 13]. By contrast, free T concentrations usually remain normal, although bioavailable T was found to be subnormal in hyperthyroid males in one study [14]. Total and free estradiol (E2) concentrations may be elevated and, consequently, the free T/free E2 ratio can be lower in hyperthyroid males compared to normal individuals [14–18]. Relative free E2 elevation may contribute to the higher incidence of gynecomastia and decreased libido observed in hyperthyroid males [19, 20]. Another consistent finding has been that luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin releasing hormone (GnRH) administration are exaggerated in hyperthyroid males, contrasting with a blunted response of Leydig cells to human chorionic gonadotropin (hCG) administration, as assessed by serum T responses [16–18]. Such abnormalities of the hypothalamic-pituitary-gonadal (HPG) axis are significantly correlated with increased serum thyroxine (T4) levels. They are reversible with restoration of the euthyroid status, so that no treatment of these TH-induced abnormalities is required (Table 1). The role of THs in testicular development and spermatogenesis and the possible interaction between HPG and the hypothalamic-pituitary-thyroid (HPT) axis are depicted in Fig. 1
Conclusions
Hyperthyroidism occurs much less commonly in children than hypothyroidism, with GD being the most common cause. Current treatment options include ATD, surgery, and RAI. Sexual behavior and semen quality may be affected in thyrotoxic men, although many of these patients may have normal androgen levels. Meanwhile, menstrual irregularities and reduced fertility are the most common reproduction related symptoms in thyrotoxic women. Though hypothyroidism in males is associated with decreased libido or impotence, little is at present known about the effects of hypothyroidism on spermatogenesis and fertility. Nonetheless, it has been suggested that in hypothyroid men, sperm morphology and motility are mainly affected, while changes in cycle length and amount of bleeding are common in hypothyroid women, who also suffer from reduced fertility and higher miscarriage rates.
The aim of this review is to provide relevant information regarding the impact of thyroid disease, starting from birth and mainly concerning hyperthyroidism and hypothyroidism, on reproduction. Hyperthyroidism occurs much less commonly in children than hypothyroidism, with Graves’ disease (GD) being the most common cause of thyrotoxicosis in children. Children born with neonatal GD have no defects in the reproductive system that could be related to hyperthyroidism. Current treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine (RAI). In males, normal thyroid function seems important, at least in some parameters, for maintenance of semen quality via genomic or non-genomic mechanisms, either by locally acting on Sertoli cells, Leydig cells, or germ cells, or by affecting crosstalk between the HPT axis and the HPG axis. Sexual behavior may also be affected in thyroxic men, although many of these patients may have normal free testosterone levels. In women, menstrual irregularities are the most common reproduction-related symptoms in thyrotoxicosis, while this disorder is also associated with reduced fertility, although most women remain ovulatory. An increase in sex hormone-binding globulin (SHBG) and androgens, thyroid autoimmunity, and an impact on uterine oxidative stress are the main pathophysiological mechanisms which may influence female fertility. Thyroid hormones are responsible for normal growth and development during pre- and postnatal life, congenital hypothyroidism (CH) being the most common cause of neonatal thyroid disorders, affecting about one newborn infant in 3500. The reproductive tract appears to develop normally in cretins. Today, CH-screening programs allow for early identification and treatment, and, as a result, affected children now achieve normal or near-normal development. Hypothyroidism in males is associated with decreased libido or impotence. Although little is currently known about the effects of hypothyroidism on spermatogenesis and fertility, it has been established that sperm morphology and motility are mainly affected. In women of reproductive age, hypothyroidism results in changes in cycle length and amount of bleeding. Moreover, a negative effect on fertility and higher miscarriage rates has also been described.
Thyrotoxicosis in males and reproduction
Hormonal changes
Thyroid hormone regulates the synthesis of two sex hormone binding (SHB) proteins [8], namely, sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, and androgen-binding protein(ABP), synthesized by the Sertoli cell [9]. ABP maintains the necessary levels of intratesticular androgen for germ cell maturation and differentiation. In rats and in humans, SHBG and ABP have the same amino acid sequence, as they are encoded by the same SHBG gene, though they differ in carbohydrate content and structure (glycosylation) [9–11].
An increase in SHBG has been a feature consistently associated with thyrotoxicosis, which state leads to increased circulating levels of total testosterone (T) and a reduction in the metabolic clearance rate of T [12, 13]. By contrast, free T concentrations usually remain normal, although bioavailable T was found to be subnormal in hyperthyroid males in one study [14]. Total and free estradiol (E2) concentrations may be elevated and, consequently, the free T/free E2 ratio can be lower in hyperthyroid males compared to normal individuals [14–18]. Relative free E2 elevation may contribute to the higher incidence of gynecomastia and decreased libido observed in hyperthyroid males [19, 20]. Another consistent finding has been that luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin releasing hormone (GnRH) administration are exaggerated in hyperthyroid males, contrasting with a blunted response of Leydig cells to human chorionic gonadotropin (hCG) administration, as assessed by serum T responses [16–18]. Such abnormalities of the hypothalamic-pituitary-gonadal (HPG) axis are significantly correlated with increased serum thyroxine (T4) levels. They are reversible with restoration of the euthyroid status, so that no treatment of these TH-induced abnormalities is required (Table 1). The role of THs in testicular development and spermatogenesis and the possible interaction between HPG and the hypothalamic-pituitary-thyroid (HPT) axis are depicted in Fig. 1
Conclusions
Hyperthyroidism occurs much less commonly in children than hypothyroidism, with GD being the most common cause. Current treatment options include ATD, surgery, and RAI. Sexual behavior and semen quality may be affected in thyrotoxic men, although many of these patients may have normal androgen levels. Meanwhile, menstrual irregularities and reduced fertility are the most common reproduction related symptoms in thyrotoxic women. Though hypothyroidism in males is associated with decreased libido or impotence, little is at present known about the effects of hypothyroidism on spermatogenesis and fertility. Nonetheless, it has been suggested that in hypothyroid men, sperm morphology and motility are mainly affected, while changes in cycle length and amount of bleeding are common in hypothyroid women, who also suffer from reduced fertility and higher miscarriage rates.
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