Normal Free Testosterone Levels Research Articles

The impact of thyroid diseases starting from birth on reproductive function.

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.

Association of Free Testosterone With Hypogonadal Symptoms in Men With Near-normal Total Testosterone Levels

To investigate the association between hypogonadal symptoms and free testosterone (FT) levels in men with near-normal total testosterone (T) levels (250-350ng/dL) and to determine whether a discriminatory threshold for FT exists below which hypogonadal symptoms become more prevalent. We reviewed the charts of 3167 men who presented to an outpatient men's health clinic. Two hundred thirty-one men had symptoms of "low testosterone" and serum testosterone levels between 250 and 350ng/dL. We evaluated hypogonadal symptoms using the Androgen Deficiency in the Adult Male (ADAM) and quantitative ADAM (qADAM) questionnaires. Serum levels of T and sex hormone-binding globulin were collected on the same day that men completed their questionnaires. We used linear regression to determine whether a threshold of FT exists for hypogonadal symptoms. We performed univariate and multivariable analyses to evaluate factors that predicted a low FT level. The median age was 43.5years, and the median testosterone and FT levels were 303ng/dL and 6.3ng/dL, respectively. Prevalence and severity of hypogonadal symptoms (ADAM and qADAM) were similar between men with low (<6.4ng/mL) and normal FT levels. There was an association between age and 3 of the 10 hypogonadal symptoms (decreased enjoyment in life, sadness, and deterioration of work performance) with a low FT on a univariate analysis. Only younger age was positively associated with FT on multivariable analysis. We did not observe a relationship between hypogonadal symptoms and FT in men with near-normal testosterone levels. Symptom-specific FT thresholds could not be defined, as age remains an important confounder.

Association Between Sex Steroid Hormones and Hematocrit in a Nationally Representative Sample of Men

Low or high hematocrit levels are associated with increased morbidity and mortality, mediated via anemia or thromboembolic events, respectively. It is therefore important to identify factors that influence hematocrit. Although androgens are known to stimulate hematopoietic cells, it is unknown whether circulating sex steroid hormones affect hematocrit. The association between serum sex steroid hormone concentrations and hematocrit in men aged ≥ 20 years was evaluated in a cross-sectional study of 1273 men in the Third National Health and Nutrition Examination Survey (1988-1991). Outcomes were low (<10th percentile), high (>90th percentile), and mean hematocrit. Men with low free testosterone levels had a lower hematocrit than men with normal free testosterone levels (P = .03), although no relationship was found between total testosterone level and hematocrit. The relationship between sex hormone-binding globulin (SHBG) and hematocrit was complex, with both low (P < .001) and high (P = .01) SHBG levels associated with lower hematocrit in men aged ≥ 20 years and only high (P = .01) SHBG levels in men aged ≥ 50 years. The odds ratio (OR) of high vs normal hematocrit increased as total estradiol (OR, 2.84; P trend = .04) and free estradiol (OR, 2.23; P trend = .09) levels increased. In this nationally representative study of men, sex steroid hormone levels, particularly low free testosterone and high SHBG levels, were associated with lower hematocrit, and high total and free estradiol levels were associated with high hematocrit. Thus, changes in sex hormone levels with aging may contribute to the increased prevalence of anemia and thromboembolic stroke in men as they age.

Free Testosterone Level Correlated with the Metabolic Abnormalities Dependent on Central Obesity in Women with Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have increased risks of developing metabolic abnormalities compared with the women without PCOS. Hyperandrogenemia is one of the most important characteristics of PCOS. However, the correlations between hyperandrogenemia and metabolic disorders are uncertain. To elucidate the relationship between androgen indices and metabolic abnormalities in Chinese women with PCOS. A retrospective analysis of the anthropometric and biochemical records of 408 women with PCOS. The prevalence of metabolic syndrome (MetS) was 15.7% in women with PCOS. No association existed between total testosterone (TT) and metabolic profile. Free testosterone (FT) correlated with most of the metabolic variables by unadjusted correlation analyses. The women with elevated FT levels exhibited more unfavorable metabolic profiles compared with the women with normal FT levels. After adjusting for the confounding factors by multivariate logistic regression analysis, the women with elevated FT levels had higher prevalence of central obesity than the women with normal FT levels (odds ratio [OR] 2.346, p=0.042). Women with reduced sex hormone-binding globulin levels were more likely to have central obesity, overweight, raised fasting glucose, insulin resistance, and raised diastolic blood pressure. Raised dehydroepiandrosterone sulfate (DHEAS) level was associated with a lower probability of having central obesity (OR 0.293, p=0.001) and overweight (OR 0.47, p=0.023). FT has closer association with metabolic parameters than TT. FT can involve in the development of metabolic disorders dependent on central obesity. Raised DHEAS level can reduce the risks of central obesity and overweight.

Free testosterone levels and implications on clinical outcomes in elderly men

Aging is accompanied by a progressive decline in serum testosterone. Evidence concerning the clinical manifestations of low serum testosterone levels is contradictory. We aimed to examine the age-related decline in testosterone and the possible clinical outcomes, including erectile dysfunction, prostatism, cognitive function, daily life activities, depression, and osteoporosis. One hundred and twenty men underwent comprehensive geriatric assessment. Testosterone and free testosterone levels were measured, geriatric assessment scales, International Index of Erectile Function (IIEF) and International Prostate Symptom Scale (IPSS) were performed, and bone mineral densities were determined. The mean age of the 120 men was 73.8+/-5.90. A significant decrease in testosterone and free testosterone levels with increasing age was determined (p=0.021). It was also found that erectile dysfunction, as determined by IIEF (r=0.66, p<0.001), and symptoms of prostatism determined by IPSS (r=-0.23, p=0.016), were significantly associated with low free testosterone levels. Laboratory parameters, obesity, osteoporosis, cognitive function, daily life activities, and cardiovascular diseases were not significantly different between groups with low and normal free testosterone levels. Age-related decrease in free testosterone may lead to erectile dysfunction and symptoms of prostatism in elderly men.

Sexual and Physical Health After Sex Reassignment Surgery

A long-term follow-up study of 55 transsexual patients (32 male-to-female and 23 female-to-male) post-sex reassignment surgery (SRS) was carried out to evaluate sexual and general health outcome. Relatively few and minor morbidities were observed in our group of patients, and they were mostly reversible with appropriate treatment. A trend toward more general health problems in male-to-females was seen, possibly explained by older age and smoking habits. Although all male-to-females, treated with estrogens continuously, had total testosterone levels within the normal female range because of estrogen effects on sex hormone binding globulin, only 32.1% reached normal free testosterone levels. After SRS, the transsexual person's expectations were met at an emotional and social level, but less so at the physical and sexual level even though a large number of transsexuals (80%) reported improvement of their sexuality. The female-to-males masturbated significantly more frequently than the male-to-females, and a trend to more sexual satisfaction, more sexual excitement, and more easily reaching orgasm was seen in the female-to-male group. The majority of participants reported a change in orgasmic feeling, toward more powerful and shorter for female-to-males and more intense, smoother, and longer in male-to-females. Over two-thirds of male-to-females reported the secretion of a vaginal fluid during sexual excitation, originating from the Cowper's glands, left in place during surgery. In female-to-males with erection prosthesis, sexual expectations were more realized (compared to those without), but pain during intercourse was more often reported.

Gonadal endocrine dysfunction in patients with lung cancer: Relation to responsiveness to chemotherapy, respiratory function and performance status

Male lung cancer patients with poor performance status [Eastern Cooperative Oncology Group (ECOG) index 3–4] have an endocrinological dysfunction as assessed by serum testosterone and sex hormone-binding globulin (SHBG) levels. Patients who respond to therapy regain normal free testosterone levels within 12 weeks post chemotherapy, whereas non-responders continue to exhibit subnormal levels. The perturbations of endocrinological variables in patients with lung cancer is not due to development of hypoxia, as patients with respiratory failure maintain a significantly lower testosterone level compared to cancer patients. The development of a deficiency in total testosterone concentrations in lung cancer patients is correlated to their performance status, and not to the presence of metastatic disease. The mechanisms responsible for the endocrinological dysfunction in patients with lung cancer remain unknown.

Studies of the relation of plasma androgen levels to androgen action in women

Testosterone-estradiol-binding-globulin (TEBG) is a major determinant of androgen disposition and action. TEBG levels, but not free testosterone levels, correlate with the metabolic clearance rate (MCR) of testosterone in normal women. This suggests that the testosterone MCR reflects androgen removal by the liver, an organ which removes a large fraction of steroid on a single passage, rather than the concentration of unbound androgen. Consequently, testosterone production seems more closely related to androgen catabolism than to androgen action. In support of this concept, we have studied a hirsute woman in whom testosterone clearance and production were elevated in the presence of a normal free testosterone level; her hirsutism seems related to androgens other than testosterone. Although testosterone is of major importance, androgen action seems to result from the net effect of several free plasma 17β-hydroxysteroids, including particularly androstenediol and dihydrotestosterone. About 25% of women with moderate male-pattern hirsutism have normal total and free plasma testosterone levels. In most such cases total 17β-hydroxysteroids are also normal. However, an abnormally low fraction of all these 17β-hydroxysteroids is bound to TEBG. As a result, an increase in the plasma “total androgenicity index” is present in this group of patients. Such women do not necessarily evidence increased testosterone production. Obesity appears to be another important determinant of androgen disposition and action. The testosterone MCR correlates well with adiposity independently of the TEBG levels in normal women. In addition, hyperandrogenism is frequently present with minimal or no hirsutism in obese women. This finding suggests that obesity increases the apparent “threshold” at which hirsutism appears in response to androgen or that obesity is a result of slight hyperandrogenism.