Free plasma testosterone levels during the normal menstrual cycle (original) (raw)
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Steroids, 2013
Background: Testosterone concentrations in normally cycling women are assumed to be elevated around the time of ovulation. The clinical relevance of changing testosterone concentrations during the menstrual cycle, however, is unclear. Poor performance of current direct immunoassays for testosterone at low concentrations confounds this issue. Therefore, our objective was to assess daily testosterone fluctuation during the menstrual cycle by a thoroughly validated isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method and to evaluate whether an ARCHITECT Ò 2nd Generation Testosterone fully automated immunoassay is equally suited for this purpose. Methods: Testosterone was measured in serum obtained daily during the menstrual cycle of 25 healthy women, characterized by biochemical and physical examination. Results: Performance of the ID-LC-MS/MS method was concordant with a published reference method (y = 1.007x À 0.056 nmol/L; r = 0.9998). Comparison of the immunoassay to ID-LC-MS/MS yielded y = 1.095x + 0.104 nmol/L (r = 0.9031). Overall, testosterone concentrations were higher mid-cycle, but a peak was not discernible in each individual. Apart from a persistent positive bias, the immunoassay measured the same testosterone profiles as the ID-LC-MS/MS method. The reference interval in women was 0.30-1.69 nmol/L (8.7-48.7 ng/dL) for ID-LC-MS/MS and 0.50-2.00 nmol/L (14.4-57.7 ng/dL) for the immunoassay. Conclusion: The elevation of mid-cycle testosterone concentrations is statistically significant, although not clinically relevant since day-to-day variation is higher and independent of the menstrual cycle. In this light, a single testosterone measurement might not be reflective of the overall testosterone status in an individual. Measurements obtained using the 2nd generation immunoassay gave comparable results across the menstrual cycle.
2019
The role of testosterone in females has not been fully elucidated. Studies usually involved postmenopausal women. Literature data on age-related changes of testosterone levels are contradictory. The application of sex hormones and their combination in medical practice increases the importance of study of the menstrual cycle fluctuations in testosterone, populational variability of testosterone and estradiol levels and their ratio in healthy females to prevent the excessive doses of sex steroids and provide the using of optimal their doses in different phases of menstrual cycle during treatment. The objective of our research was to evaluate testosterone and estradiol levels, their interrelation and their ratio in different stages of menstrual cycle in young healthy women. Twenty-two young Ukrainian females aged 18 to 22 years were enrolled in this study. Testosterone and estradiol levels in blood serum were determined by Estradiol ELISA and Testosterone ELISA kits (Italy). Both estra...
Analysis of testosterone pulsatility in women with ovulatory menstrual cycles
Arquivos Brasileiros de Endocrinologia & Metabologia, 2009
To evaluate the pattern of the pulsatile secretion of testosterone in normal menstrual cycle. Methods: Eight healthy women with ovulatory menstrual cycles were enrolled. Blood samples were collected at ten-minute intervals for six hours, starting between 7 and 8 am, after a ten-hour fasting, in three phases: mid-follicular (Day 7), late follicular (Day 12) and mid-luteal phase (Day 21). Samples were assayed for testosterone, LH and the baseline also for SHBG. Results: Testosterone pulse frequency, mean amplitude pulse, percentage of increment in pulse amplitude, mean duration of pulses and pulse interval were similar in the three phases. LH pulsatility was statistically different among the three phases (p < 0.001) representing normal ovulatory cycles. Conclusions: These data increase the knowledge about the testosterone secretion profile in the human menstrual cycle and can be used as a contribution to clinical investigation in both hyperandrogenism and androgen insufficiency syndrome. Arq Bras Endocrinol Metab. 2009;53(8):1040-6 Keywords Testosterone; pulse; menstrual cycle RESUMO Objetivo: Avaliar o padrão pulsátil da secreção da testosterona em mulheres normais. Métodos: Oito mulheres saudáveis com ciclos ovulatórios foram selecionadas. Amostras sanguíneas foram coletadas a cada dez minutos durante seis horas, começando entre 7 e 8 h da manhã, após dez horas de jejum, nas três fases do ciclo menstrual: folicular média (Dia 7), folicular tardia (Dia 12) e lútea (Dia 21). Foram mensurados: testosterona, LH e, no basal, também SHBG. Resultados: A frequência dos pulsos de testosterona, média da amplitude do pulso, porcentagem do incremento da amplitude, duração e intervalos dos pulsos foram similares nas três fases (p > 0,05). A pulsatilidade do LH foi estatisticamente diferente entre as três fases (p < 0,001), caracterizando padrão característico do ciclo ovulatório normal. Conclusões: Esses dados aumentam o conhecimento sobre o padrão de secreção da testosterona no ciclo menstrual humano e representam uma contribuição para a investigação clínica, tanto no hiperandrogenismo como na síndrome de insuficiência androgênica. Arq Bras Endocrinol Metab. 2009;53(8):1040-6
Not Only Estradiol but Also Testosterone Levels Depend on Menstrual Cycle Phases
Inter Collegas
The role of testosterone in females has not been fully elucidated. Studies usually involved postmenopausal women. Literature data on age-related changes of testosterone levels are contradictory. The application of sex hormones and their combination in medical practice increases the importance of study of the menstrual cycle fluctuations in testosterone, populational variability of testosterone and estradiol levels and their ratio in healthy females to prevent the excessive doses of sex steroids and provide the using of optimal their doses in different phases of menstrual cycle during treatment. The objective of our research was to evaluate testosterone and estradiol levels, their interrelation and their ratio in different stages of menstrual cycle in young healthy women. Twenty-two young Ukrainian females aged 18 to 22 years were enrolled in this study. Testosterone and estradiol levels in blood serum were determined by Estradiol ELISA and Testosterone ELISA kits (Italy). Both estradiol and testosterone levels depended on menstrual cycle phases. The highest testosterone level was revealed in ovulation. No correlation between blood serum testosterone and estradiol levels was found in all menstrual cycle phases. Differences in testosterone and estradiol levels between Ukrainian women and some other populations of women were noted, indicating that such differences must be taken into account when treating women of different populations. Testosterone/estradiol ratio was not changed during menstrual cycle. Because of the constancy of the ratio of testosterone to estradiol during menstrual cycle and the age-related change in that ratio, this must be taken into account in the treatment of elderly women in order to create a testosterone-estradiol ratio that is characteristic of young women.
Journal of Steroid Biochemistry, 1982
A mathematical model for the calculation of free and protein bound concentrations of testosterone and estradiol in plasma is presented. The method is based on the knowledge of the total concentrations of all steroids competing for the same binding site on testosterone-estradiol-binding globulin (TeBG). the concentration of albumin. the binding capacity of TeBG. and the association constants of the steroids to the two binding proteins. For the calculations we have determined the totai concentrations of testosterone and estradiol. TeBG binding capacity. albumin concentration and the association constants for the binding of testosterone. estradio) and %dihydrotestosterone (DHT) to TeBG and albumin at 37% Physiological concentrations of some androgen metabolites reported in the literature were also included in the calculations_ namely: DHT, S-androstene-3~.t 7j?-dioi (Ae) and So-androstane-3~,17~-dioi (Aa). The binding constants for Ae and Aa to TeBG and albumin were also from the literature. Mean values of testosterone were calculated for 11 normal men and expressed as percentages of total: 2.0:; was unbound. 53-W;, bound to albumin and 43-457; bound to TeBG. For I6 normal women of a fertile age the corresponding values were 1.5'5,. 36-374, and 62");. For estradiol they were 2.4", 68-709, and 28-300, in the men and 2.c,.,. SZJ?, and 45-46", in the women. Variations in the concentrations of DHT. Ae and Aa did not influence the free concentrations of testosterone and estradiol to any significant extent. It was furthermore concluded that the androgen metabolites could be omitted from the calculations without affecting the calculated concentrations.
The Journal of Sexual Medicine, 2008
There is currently neither a clinically useful, reliable and inexpensive assay to measure circulating levels of free testosterone (T) in the range observed in women, nor is there agreement on the serum free T threshold defining hypoandrogenism that is associated with female-impaired sexual function. Aim. Following the Clinical and Laboratory Standards Institute guidelines, we generated clinically applicable ranges for circulating androgens during specific phases of the menstrual cycle in a convenience sample of 120 reproductive-aged, regularly cycling healthy European Caucasian women with self-reported normal sexual function. Methods. All participants were asked to complete a semistructured interview and fill out a set of validated questionnaires, including the Female Sexual Function Index, the Female Sexual Distress Scale, and the 21-item Beck's Inventory for Depression. Between 8 am and 10 am, a venous blood sample was drawn from each participant during the midfollicular (day 5 to 8), the ovulatory (day 13 to 15), and the midluteal phase (day 19 to 22) of the same menstrual cycle. Main Outcome Measures. Serum levels of total and free testosterone, D4-androstenedione, dehydroepiandrosterone sulphate and sex hormone-binding globulin during the midfollicular, ovulatory and midluteal phase of the same menstrual cycle. Results. Total and free T levels showed significant fluctuations, peaking during the ovulatory phase. No significant variation during the menstrual cycle were observed for D4-androstenedione and dehydroepiandrosterone sulphate. Despite the careful selection of participants that yielded an homogeneous group of women without sexual disorders, we observed a wide range of distribution for each of the circulating androgens measured in this study. Conclusions. This report provides clinically applicable ranges for androgens throughout the menstrual cycle in reproductive-aged, regularly cycling, young healthy Caucasian European women with self-reported normal sexual function. Salonia A, Pontillo M, Nappi RE, Zanni G, Fabbri F, Scavini M, Daverio R, Gallina A, Rigatti P, Bosi E, Bonini PA, and Montorsi F. Menstrual cycle-related changes in circulating androgens in healthy women with self-reported normal sexual function. J Sex Med 2008;5:854-863.
Testosterone Reference Ranges in Normally Cycling Healthy Premenopausal Women
The Journal of Sexual Medicine, 2011
At present, there are no well-accepted reference ranges for serum testosterone concentrations in women. The aim of this study was to determine the reference ranges for serum testosterone and sex hormone-binding globulin (SHBG) in premenopausal women with normal menstrual cycles. We measured serum total, free, and bioavailable testosterone and SHBG concentrations in 161 healthy, normally cycling women (18-49 years). Morning blood samples were collected during follicular, mid-cycle, and luteal phases of the menstrual cycle and analyzed using validated methods. Mean, median, and weighted average hormone levels across menstrual cycle phases as well as percentiles for a typical 30-year-old woman were determined. Age-related serum levels of total, free, and bioavailable testosterone and SHBG levels in normally cycling premenopausal women. Serum testosterone concentrations exhibited an age-related decline, whereas SHBG remained relatively stable across studied age ranges. Reference ranges for total, free, and bioavailable testosterone and SHBG were established using 5th and 95th percentiles. The estimated 5th and 95th percentiles for a 30-year-old woman were: testosterone, 15-46 ng/dL (520-1595 pmol/L); free testosterone, 1.2-6.4 pg/mL (4.16-22.2 pmol/L); calculated free testosterone, 1.3-5.6 pg/mL (4.5-19.4 pmol/L); bioavailable testosterone, 1.12-7.62 ng/dL (38.8-264.21 pmol/L); and SHBG 18-86 nmol/L. The variations of hormones and SHBG across menstrual cycle were consistent with previous literature. Reference ranges for free, total, and bioavailable testosterone and SHBG were established in premenopausal women using validated immunoassays and an adequate number of subjects consistent with recommendations by the National Committee for Clinical Laboratory Standards. The increase in testosterone in the mid-cycle period is relatively small compared with the overall variability, so these reference ranges can be applied irrespective of the day in the menstrual cycle the sample has been taken.
Steroids, 2011
Measuring serum androgen levels in women has been challenging due to limitations in method accuracy, precision sensitivity and specificity at low hormone levels. The clinical significance of changes in sex steroids across the menstrual cycle and lifespan has remained controversial, in part due to these limitations. We used validated liquid chromatography tandem mass spectrometry(LC-MS/MS) assays to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy premenopausal females and in 19 postmenopausal females. Samples were obtained in ovulatory women in the early follicular phase (EFP), midcycle and mid luteal phase (MLP). Overall, the levels of T, DHT, E2 and E1 in premenopausal women measured by LCMS/MS were lower overall than previously reported with immunoassays. In premenopausal women, serum T, Free T, E2, E1 and SHBG levels peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In postmenopausal women, T, free T, SHBG and DHT were significantly lower than in premenopausal women, concomitant with declines in E2 and E1. These data support the hypothesis that the changes in T and DHT that occur across the cycle may reflect changes in SHBG and estrogen, whereas in menopause, androgen levels decrease. LC-MS/MS may provide more accurate and precise measurement of sex steroid hormones than prior immunoassay methods and can be useful to assess the clinical significance of changes in T, DHT, E2 and E1 levels in females.
Journal of Clinical Endocrinology and Metabolism, 2000
The aims of this study were to describe, in relation to date of final menses, the average androgen levels of women in the years before and after this date, and to determine the extent to which these average levels were dependent on age and body mass index (BMI) and the degree of tracking in residual androgen levels, or the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses. Serial levels of serum sex hormone-binding globulin (SHBG), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured annually in 172 women from the Melbourne Women’s Midlife Health Project who experienced a natural menopause during 7 yr of follow-up. Fasting blood samples were drawn between days 4–8 if women were still menstruating or after 3 months of amenorrhea. The free androgen index (FAI) was calculated as the ratio of T to SHBG 3 100. Means of the log-transformed androgen levels were analyzed as a double logistic function of time relative to FMP as well as age and BMI, and correlations between repeated androgen levels were measured. Mean SHBG levels decreased by 43% from 4 yr before to 2 yr after the FMP. The time of most change was 2 yr before FMP [95% confidence interval (CI), 0.8 –3.2]. Journal of Clinical Endocrinology and Metabolism 2000; 85(8):2832-2838.