Testosterone In Women Research Articles

Testosterone Use in Women: How Safe is it?

Treatment of sex hormones deficiencies in men and women is a subject of considerable discussion due in no small measure to safety concerns. In order to appreciate the appropriate balance between potential risk and benefit, it is important to understand the issues at hand. This is particularly true in the case of the use of testosterone in women. To understand the effect of testosterone supplementation in deficient patients, it is useful to review the normal physiology of testosterone in women. An understanding of the impact of testosterone deficiency will further elucidate perspectives on the topic. This paper aims to present a rational consideration of the known and potential adverse effects of testosterone supplementation in women. Areas of concern regarding the use of androgens in women generally fall into three categories: masculinization, cardiovascular effects and cancer risks, but there are a variety of other issues to be borne in mind. Full understanding of these risks in the context of treating females experiencing testosterone deficiency is limited in some cases, and inferences have to be drawn from other areas.

Polycystic ovary syndrome and the differential diagnosis of hyperandrogenism

Key content The presence of clinical or biochemical evidence of hyperandrogenism is a defining feature of polycystic ovary syndrome (PCOS). As the criteria for diagnosing PCOS becomes more inclusive, there is an increased risk of misdiagnosing women with other causes of hyperandrogenism. Biochemical testing for serum testosterone concentrations in women has important limitations. Patients with concerning features should be investigated for other causes of hyperandrogenism. Learning objectives To review the different criteria for diagnosing PCOS and the repercussions for disease prevalence. To learn about the differential diagnosis of hyperandrogenism. To learn about the limitations of biochemical testing for testosterone in women. Ethical issues Hyperandrogenism causing hirsutism and virilisation can have significant effects on physical and psychological wellbeing. Misdiagnosis can delay appropriate treatment and may affect future fertility.

Tongkat Ali as a Potential Herbal Supplement for Physically Active Male and Female Seniors—A Pilot Study

Tongkat Ali (Eurycoma longifolia; TA) is known to increase testosterone levels and alleviate aging males' symptoms. This study aimed at investigating TA as an ergogenic supplement for elderly people. Thirteen physically active male and 12 physically active female seniors (57-72 years) were supplemented with 400-mg TA extract daily for 5 weeks. Standard hematological parameters were taken. In addition, the concentrations of total and free testosterone, dihydroepiandrosterone, cortisol, insulin-like growth factor-1, and sex hormone-binding globulin were analyzed. As additional biochemical parameters, blood urea nitrogen and creatine kinase as parameters of kidney function and muscle damage, respectively, as well as the muscle strength by a simple handgrip test were determined. After treatment, hemoglobin, testosterone, and dihydroepiandrosterone concentrations, and the ratio of total testosterone/cortisol and muscle force remained significantly lower in female seniors than in male seniors. Hematocrit and erythrocyte count in male seniors increased slightly but were significantly higher than in female seniors. Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The increase in free testosterone in women is thought to be due to the significant decline in sex hormone-binding globulin concentrations. The study affirms the ergogenic benefit of TA through enhanced muscle strength.

Acupuncture for ovulation induction in polycystic ovary syndrome: a randomized controlled trial

Acupuncture has been demonstrated to improve menstrual frequency and to decrease circulating testosterone in women with polycystic ovary syndrome (PCOS). Our aim was to investigate whether acupuncture affects ovulation frequency and to understand the underlying mechanisms of any such effect by analyzing LH and sex steroid secretion in women with PCOS. This prospective, randomized, controlled clinical trial was conducted between June 2009 and September 2010. Thirty-two women with PCOS were randomized to receive either acupuncture with manual and low-frequency electrical stimulation or to meetings with a physical therapist twice a week for 10-13 wk. Main outcome measures were changes in LH secretion patterns from baseline to after 10-13 wk of treatment and ovulation frequency during the treatment period. Secondary outcomes were changes in the secretion of sex steroids, anti-Müllerian hormone, inhibin B, and serum cortisol. Ovulation frequency during treatment was higher in the acupuncture group than in the control group. After 10-13 wk of intervention, circulating levels of estrone, estrone sulfate, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, free testosterone, dihydrotestosterone, androsterone glucuronide, androstane-3α,17β-diol-3-glucuronide, and androstane-3α,17β-diol-17-glucuronide decreased within the acupuncture group and were significantly lower than in the control group for all of these except androstenedione. We conclude that repeated acupuncture treatments resulted in higher ovulation frequency in lean/overweight women with PCOS and were more effective than just meeting with the therapist. Ovarian and adrenal sex steroid serum levels were reduced with no effect on LH secretion.

Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

There are technical limitations for the currently available methods of measuring serum total and free testosterone in females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), and calculated free testosterone (CFT) in the assessment of androgen status in women investigated for suspected hyperandrogenism. This is a case control study that was conducted during the period from 1(st) May 2011 to 31(st) October 2011 on 122 patients aged (18-45 years) whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18). The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19), hirsutism (group 3; n=18), menstrual disturbances (irregularities) or infertility (group 4; n=49), as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5; n=18). Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation. There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG <30 nmol/L, FAI >5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73.5% elevated FAI and CFT, respectively; compared with 53.1% for testosterone, while in group 5, patients had 83.3% and 88.9% elevated FAI and CFT, respectively, compared with 61.1% for testosterone. The diagnosis of hyperandrogenism was most obvious when using CFT or FAI than testosterone alone. It is thus recommended to include these calculated parameters (CFT and/or FAI) in the routine investigation and assessment of women with disorders related to clinical or biochemical hyperandrogenism.

Assessment of theca cell function: a prerequisite to androgen or luteinizing hormone supplementation in poor responders

Poor responders are a heterogeneous population, with some patients displaying a diminished ovarian reserve and others a poor ovarian reserve with preserved granulosa cell function. Androgen and LH/hCG supplementation has been advocated for poor responders, mainly those >40 years old. Although androgens synergistically act with FSH to support folliculogenesis, and ovarian androgen secretion declines with age, there is still no evidence that androgen therapy is actually effective to improve ovarian FSH sensitivity. The main reason seems to be that theca cell function has not been appropriately assessed in patients at risk of poor response. The definition of theca insufficiency is hampered by methodologic shortcomings in routine bioassays. Provocative tests for theca cells might help to identify those patients who could benefit from androgen supplementation. The lack of data regarding theca cells in these patients might contribute to explaining the absence of evidence for a positive effect of androgen therapy.

Association of circulating adiponectin with testosterone in women during the menopausal transition

ObjectiveWe examined (1) the change in circulating adiponectin in women during the menopausal transition and (2) the associations of adiponectin levels with estrogen, androgen and sex hormone-binding globulin (SHBG) in women during the menopausal transition. MethodsWe conducted a cross-sectional study in 235 healthy women and divided them into 7 stages by menstrual regularity and follicle-stimulating hormone (FSH) level. Serum levels of adiponectin, estradiol, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and SHBG were measured. Levels of free and bioavailable testosterone were calculated by using total testosterone, albumin and SHBG. ResultsSerum adiponectin levels showed a U-curve, levels being low in early and late menopausal transition and gradually becoming higher after menopause. Adiponectin levels were negatively correlated with levels of free testosterone, bioavailable testosterone and DHEA-S and were positively correlated with SHBG in postmenopausal women for whom more than 1 year had passed since menopause. Adiponectin level was not correlated with estradiol level. ConclusionCirculating adiponectin level shows a U-curve during the menopausal transition and adiponectin level is associated with levels of free and bioavailable testosterone and DHEA-S in postmenopause.

Out of Bounds? A Critique of the New Policies on Hyperandrogenism in Elite Female Athletes

In May 2011, more than a decade after the International Association of Athletics Federations (IAAF) and the International Olympic Committee (IOC) abandoned sex testing, they devised new policies in response to the IAAF's treatment of Caster Semenya, the South African runner whose sex was challenged because of her spectacular win and powerful physique that fueled an international frenzy questioning her sex and legitimacy to compete as female. These policies claim that atypically high levels of endogenous testosterone in women (caused by various medical conditions) create an unfair advantage and must be regulated. Against the backdrop of Semenya's case and the scientific and historical complexity of “gender verification” in elite sports, we question the new policies on three grounds: (1) the underlying scientific assumptions; (2) the policymaking process; and (3) the potential to achieve fairness for female athletes. We find the policies in each of these domains significantly flawed and therefore argue they should be withdrawn.

Testosterone Supplementation for Hypoactive Sexual Desire Disorder in Women

Over 50% of women are believed to be affected by female sexual dysfunction (FSD). When particularly distressful, FSD is known as hypoactive sexual desire disorder (HSDD). In contrast to male sexual dysfunction that has been extensively researched, there is less evidence addressing the treatment of HSDD in women, particularly with regard to the use of androgen therapy. A variety of testosterone products, including oral, injectable, and transdermal preparations, has been prescribed for the treatment of HSDD in premenopausal women, as well as in those with naturally occurring or surgically induced menopause. Although studies have shown some benefit with testosterone supplementation in women with HSDD, conflicting evidence and debate regarding the clinical efficacy of testosterone remain. Because of concern over potential adverse events, additional studies with longer follow-up periods are necessary before use of testosterone in women with HSDD becomes widespread. Initiation of testosterone therapy must be considered on an individual basis after a thorough discussion with the patient about risks and benefits.

Reference ranges for total and calculated free and bioavailable testosterone in a young healthy women population with normal menstrual cycles or using oral contraception

ObjectiveDetermine reference values for testosterone in women. Design and methods18–40Year-old women with regular menses or using oral contraception were assessed by questionnaire and blood sample. ResultsIn 155 women, reference values were different between women with and without hyperandrogenism for total testosterone (0.48–3.42 vs. 0.54–2.72nmol/L) and calculated free (3–65 vs. 3–39pmol/L) and bioavailable (0.06–1.35 vs. 0.06–0.81nmol/L) testosterone. ConclusionUpper reference values for testosterone in women must be established from a well-characterized population.

Assessment of androgen concentration in women: liquid chromatography–tandem mass spectrometry and extraction RIA show comparable results

The measurement of serum testosterone in women is challenging due to lack of trueness, precision, and sensitivity of various available testosterone assays. Accurate assessment of testosterone in women is crucial especially in conditions associated with alleged over- or under-production of testosterone, such as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI). The aim of this study was to measure and compare androgen concentrations in women with PCOS, POI, and female controls and to evaluate the performance of extraction RIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in these women. Cross-sectional study. Carefully phenotyped women with POI (n=208) or PCOS (n=200) and 45 healthy, regularly cyclic female controls were included. Method comparison analyses were performed for total testosterone, androstenedione (AD), and DHEA, as measured by LC-MS/MS and extraction RIA. All androgen levels were significantly elevated in women with PCOS compared with POI patients (P<0.05) and controls (P<0.05). Women with POI presented with similar androgen concentrations as controls, except for AD. Compared with measurements by extraction RIA, testosterone, DHEA, and AD concentrations measured by LC-MS/MS were systematically lower. However, using extraction RIA and LC-MS/MS, testosterone, DHEA, and AD measurements were shown to have good agreement as assessed by Bland-Altman analysis and intraclass correlation coefficient: 0.95 (95% confidence interval 0.94-0.91), 0.83 (0.79-0.86), and 0.96 (0.95-0.97) respectively. LC-MS/MS, compared with a labor-intensive extraction RIA, shows good precision, sensitivity, and high accuracy for measuring female testosterone, DHEA, and AD concentrations under various clinical conditions. LC-MS/MS, therefore, represents a convenient and reliable assay for both clinical and research purposes, where androgen measurement in women is required.

Schizophrenia and Stein–Leventhal syndrome: comorbidity features

To explore shared pathogenesis between schizophrenia and polycistic ovary syndrome (PCOS). Ninety-six studies of schizophrenia and PCOS from a mean sample of 139 women are recruited from PubMed and FASTSTATS for geometrical regression analysis. Parametric and observational properties of both diseases (gene polymorphism, monoamines, gonadal steroids, gonadotropins, thyroid hormones, insulin sensitivity index, hirsute index, oligomenorrhea, anhedonia, asociality, apathy, emotional withdrawal, alogia, poor rapport, stereotypical thinking, hyperkinetic reactions, treatment with valproate) are stochastically distributed in the elliptical area. Results of both analyses suggest that insulin resistance and elevated testosterone are predictive to comorbidity. These associations are stronger with calculation from elliptical model (r (2) = 0.92) than a traditional regression analysis (r (2) = 0.65). Insulin resistance and elevated testosterone in women contribute in shared pathogenesis of schizophrenia and PCOS. 3D regression analysis shows greater strength of association with the "criterion" value.

Cardiovascular and cancer safety of testosterone in women

To examine the recent data pertaining to the relationships between testosterone and cardiovascular disease (CVD) and cancer in women. Despite the entrenched belief that higher blood levels of testosterone increase the risk of CVD in women, data from recent observational studies mostly show an inverse relationship between testosterone and CVD risk. One pilot study suggests favorable effects of nonoral testosterone treatment of women with established congestive cardiac failure which merits further evaluation. The relationship between endogenous testosterone production and breast cancer risk remains contentious, with recent studies indicating either no relationship, or a possible increase in risk when estrone and estradiol are not taken into account. No randomized controlled trial of testosterone therapy has been sufficiently large or of sufficient duration to establish whether such treatment may influence breast cancer occurrence. There does not appear to be an association between testosterone and endometrial cancer, or other malignancies on review of published studies. Testosterone is inversely associated with increased CVD risk in women, whereas low sex hormone binding globulin increases CVD risk. The relationship between testosterone and breast cancer remains unclear, although a clear signal of risk has not emerged from studies of women treated with testosterone therapy over the past decade.

Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.

Total Testosterone Assays in Women with Polycystic Ovary Syndrome: Precision and Correlation with Hirsutism

There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement. The aim was to compare assay results from a direct RIA with two LC/MS. We conducted a blinded laboratory study including masked duplicate samples at three laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS). Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared. We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores. Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (≤50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17). A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels.

Changes in estradiol predict within-women shifts in attraction to facial cues of men's testosterone

Many studies have demonstrated that women express stronger attraction to androgen-related traits when tested near ovulation than when tested at other times in the cycle. Much less research, however, has directly addressed which hormonal or other physiological signals may regulate these temporal shifts in women's attractiveness judgments. In the present study, we measured women's preferences for facial cues of men's testosterone concentrations on two occasions spaced two weeks apart, while also measuring women's salivary estradiol and testosterone concentrations at each testing session. Changes in women's estradiol concentrations across sessions positively predicted changes in their preferences for facial cues of high testosterone; there was no such effect for changes in women's testosterone concentrations. For the subset of women who had a testing session fall within the estimated fertile window, preferences for high testosterone faces were stronger in the fertile window session, and change in estradiol from outside to inside the fertile window positively predicted the magnitude of the ovulatory preference shift. These patterns were not replicated when testing preferences for faces that were rated as high in masculinity, suggesting that facial cues of high testosterone can be distinguished from the cues used to subjectively judge facial masculinity. Our findings suggest that women's estradiol promotes attraction to androgen-dependent cues in men (similar to its effects in females of various nonhuman species), and support a role for this hormone as a physiological regulator of cycle phase shifts in mating psychology.

Perte d'information diagnostique par utilisation de méthodes non recommandées pour le dosage de la testostérone chez la femme

French and US endocrine societies recommend using GC-MS or RIA after purification (extraction + chromatography) to assess blood levels of testosterone in women. However, most of laboratories use automatized methods that have to be reserved to measure testosterone levels in men. The aim of this study was to show the consequences of analytical discrepancies of some immunological methods on the diagnostics values of testosterone levels assayed in women. Compared to GC-MS the correlations of the assayed levels varied (Spearman's rank correlation coefficients: 0.935; 0.793; 0.841; 0.852 respectively for RIA Immunotech™ with extraction and chromatographic purification; Testosterone Access-DxI800®; Testosterone Immulite 2000®; Testosterone II Cobas E601®). The testosterone levels allowed an accurate conclusion in 95.2 %; 75.8 %; 77.4 %; 89.8 % of patients, respectively. The agreement with GC-MS results was very good for RIA method (κ=0,840), moderate for DxI800® method (κ=0,414), moderate for Immulite® method (κ=0,467), good for Cobas® method (κ=0,667). Most of discordances are false hypertestosteronemia. The use of non recommended methods may leads to nosological errors (misclassification rates of 10to 25% with automatized methods) that causes loss of chance in part of female patients.

Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients

Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. Prospective cohort study with a 4.5-year follow-up period. From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. At baseline, the study population was aged 57.96±14.37 years with a mean body mass index of 26.71±5.17 kg/m(2). No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2-Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2-Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33-0.74; adjusted HR 0.62, 95% CI 0.42-0.939; CV events: Q2-Q5 versus Q1: crude HR 0.54, 95% CI 0.38-0.77; adjusted HR 0.68, 95% CI 0.48-0.97). Kaplan-Meier curves revealed similar data. Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

Prejudice and truth about the effect of testosterone on human bargaining behaviour

Both biosociological and psychological models, as well as animal research, suggest that testosterone has a key role in social interactions. Evidence from animal studies in rodents shows that testosterone causes aggressive behaviour towards conspecifics. Folk wisdom generalizes and adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic, or even aggressive human behaviours. However, many researchers have questioned this folk hypothesis, arguing that testosterone is primarily involved in status-related behaviours in challenging social interactions, but causal evidence that discriminates between these views is sparse. Here we show that the sublingual administration of a single dose of testosterone in women causes a substantial increase in fair bargaining behaviour, thereby reducing bargaining conflicts and increasing the efficiency of social interactions. However, subjects who believed that they received testosterone-regardless of whether they actually received it or not-behaved much more unfairly than those who believed that they were treated with placebo. Thus, the folk hypothesis seems to generate a strong negative association between subjects' beliefs and the fairness of their offers, even though testosterone administration actually causes a substantial increase in the frequency of fair bargaining offers in our experiment.

The effects of partner togetherness on salivary testosterone in women in long distance relationships

The present study examined whether women's testosterone levels are influenced by being with a sexual and romantic partner after a period of sexual abstinence. Women in long distance relationships ( n = 15) provided five saliva samples: at least 1 week before seeing their partner (and at least 2 weeks since their last visit), the day before seeing their partner, when they were with their partner but prior to engaging in sexual activity, the day after their first sexual activity, and 3 days after they were separated from their partners. Salivary testosterone was lowest when participants had been away from their partners for at least 2 weeks and highest the day before they were to see their partners and the day after sexual activity. Results from this study indicated that women's testosterone increased both the day before they were with their partners and they day after they first engaged in sexual activity. However, something about initially reuniting with their partners returned their testosterone to baseline levels, which may be an effect of being in the same location as a partner, or just a state fluctuation due to nervousness or other psychological state.