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BMC Women's Health May 2023Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various...
INTRODUCTION
Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various diseases related to reproductive hormones in postmenopause have received much attention. LH and FSH are also known to be associated with activities of enzymes related to reproductive hormones. We examined the associations of LH and FSH with androgens and estrogens in each stage of the menopausal transition according to a classification from menopausal transition to postmenopause.
METHODS
This study was a cross-sectional design. We basically used the Stage of Reproductive Aging Workshop (STRAW) + 10. We divided the 173 subjects into 6 groups according to menstrual regularity and follicle-stimulating hormone level: mid reproductive stage (Group A), late reproductive stage (Group B), early menopausal transition (Group C), late menopausal transition (Group D), very early postmenopause (Group E) and early postmenopause (Group F). Levels of LH, FSH, dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and androstenediol were measured.
RESULTS
In Group A, LH showed significant positive correlations with androstenedione and estrone. In Group D, LH was positively associated with T and free T and was negatively associated with estradiol. In Groups B, C, D and F, LH showed significant positive correlations with FSH, and there was a tendency for an association between LH and FSH in Group E. FSH was associated with estradiol but not with estrone in Groups C and D.
CONCLUSION
The associations of LH and FSH with reproductive hormones are different depending on the stage of the menopausal transition.
TRIAL REGISTRATION
Trial registration number 2356-1; Date of registration: 18/02/2018, retrospectively registered.
Topics: Female; Humans; Androstenedione; Estrone; Follicle Stimulating Hormone; Cross-Sectional Studies; Luteinizing Hormone; Menopause; Estradiol; Androgens; Testosterone
PubMed: 37231423
DOI: 10.1186/s12905-023-02438-5 -
Singapore Medical Journal Nov 2011Congenital adrenal hyperplasia (CAH) or adrenogenital syndrome is the most common cause of female ambiguous genitalia. Management of such patients involves medical...
INTRODUCTION
Congenital adrenal hyperplasia (CAH) or adrenogenital syndrome is the most common cause of female ambiguous genitalia. Management of such patients involves medical treatment using glucocorticoids such as hydrocortisone, prednisone or dexamethasone. Monitoring is done by measurement of 17-hydroxyprogesterone (17-OHP) or androstenedione in serum, plasma or saliva. The aim of this study was to develop a system of monitoring steroid treatment in CAH patients using only saliva.
METHODS
We studied the saliva of 24 CAH patients who received glucocorticoid replacement therapy. The patients were asked to collect saliva upon awakening, and in the afternoon and evening. The levels of 17-OHP and androstenedione in the saliva as well as in serum were then measured by immunoassay.
RESULTS
There was a significant positive correlation between 17-OHP in serum and in saliva (R equals 0.929, p-value less than 0.01). A significant positive correlation between androstenedione level in saliva and serum was also found (R equals 0.611, p-value less than 0.01). This study also revealed a significant positive correlation between androstenedione and 17-OHP in serum (R equals 0.647, p-value less than 0.01) and saliva (R equals 0.799, p-value less than 0.01). All patients showed increased level of 17-OHP and androstenedione in the sample collected upon awakening.
CONCLUSION
Determination of salivary androstenedione and 17-OHP in CAH patients could be a useful alternative to the measurement of these hormones in serum.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Androstenedione; Child; Child, Preschool; Disorders of Sex Development; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Hydrocortisone; Infant; Plasma; Saliva; Time Factors
PubMed: 22173250
DOI: No ID Found -
Journal of Inorganic Biochemistry Jul 2018Cytochrome P450 19 (CYP19, aromatase) catalyzes the conversion of androgens to estrogens in a sequence of three reactions that each depend on NADPH and O. Aromatase is a...
Cytochrome P450 19 (CYP19, aromatase) catalyzes the conversion of androgens to estrogens in a sequence of three reactions that each depend on NADPH and O. Aromatase is a phylogenetically-ancient enzyme and its breadth of expression in other species has highlighted distinct physiological functions. In songbirds, estrogen production is required for programming the neural circuits controlling song and in the determination of sex in fish and reptiles. This work describes the expression, purification, and biophysical characterization of Aptenodytes forsteri (Emperor penguin, af) aromatase. Using human cytochrome P450 reductase as a redox partner, afCYP19 displayed similar substrate turnover and LC/MS/MS confirmed that afCYP19 catalyzes the transformations through the intermediates 19-hydroxy- and 19-oxo-androstenedione. Androstenedione and anastrozole had the highest affinity for the enzyme and were followed closely by 19-hydroxyandrostenedione and testosterone. The affinity of 19-oxo-androstenedione for afCYP19 was ten-fold lower. The time-dependent changes in the Soret bands observed in stopped-flow mixing experiments of the steroidal ligands and the inhibitor anastrozole with afCYP19 were best described by a two-step binding mechanism. In summary, these studies describe the first biophysical characterization of an avian aromatase that displays strikingly similar enzyme kinetics and ligand binding properties to the human enzyme and could serve as a convenient model system for studies of the enigmatic transformation of androgens to estrogens.
Topics: Anastrozole; Androstenedione; Aromatase; Cytochrome P-450 Enzyme System; Spectrum Analysis, Raman; Testosterone
PubMed: 29684698
DOI: 10.1016/j.jinorgbio.2018.04.002 -
Gynecological Endocrinology : the... Jun 2023To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, -acetylcysteine, vitamin B, and -adenosyl-L-methionine) for the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, -acetylcysteine, vitamin B, and -adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS).
METHODS
This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy.
RESULTS
A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of -0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups.
CONCLUSIONS
This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.
Topics: Female; Humans; Androstenedione; Antioxidants; Insulin Resistance; Menstruation Disturbances; Polycystic Ovary Syndrome; Prospective Studies; Quality of Life; Contraceptives, Oral; Dietary Supplements
PubMed: 37356455
DOI: 10.1080/09513590.2023.2227277 -
The British Journal of Surgery Feb 2019The impact of radiotherapy (RT) for rectal cancer on ovarian androgen production is unknown. The aim was to examine the effect of RT for rectal cancer on androgen levels... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The impact of radiotherapy (RT) for rectal cancer on ovarian androgen production is unknown. The aim was to examine the effect of RT for rectal cancer on androgen levels in non-oophorectomised women and the association with female sexual desire.
METHOD
This prospective cohort study included women treated with surgery for rectal cancer with or without RT. Serum testosterone (T), free T, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) were assessed at baseline, after RT and one year postoperatively. Sexual desire was assessed with the Female Sexual Function Index.
RESULTS
Twenty-seven participants had surgery alone (RT-) and 98 had preoperative RT and surgery (RT+). During the first year after surgery, median T and free T decreased from 0.6 (range 0.1–3.6) to 0.5 (0.1–2.3) nmol/L (p<0.001) and 9.1 (range 1.6–45.8) to 7.9 (1.4–22.7) pmol/L (p<0.001) respectively in the RT+ group and did not change in the RT- group. Longitudinal regression analysis confirmed a decrease in T and free T after RT. The adjusted change in androstenedione and DHEA-S was not significant in any group. The mean change in T (OR 2.74 (95% CI 1.06–7.11, p=0.038), free T (OR 1.08 (95% CI 1.02–1.15), p=0.011) and androstenedione (OR 1.52 (95% CI 1.07–2.16), p=0.019 was related to change in sexual desire.
CONCLUSION
Radiotherapy decreases androgens predominantly derived from the ovaries, while androgens of mainly adrenal origin remain unchanged. Reduction in ovarian derived androgens maybe associated with reduced sexual desire.
Topics: Aged; Aged, 80 and over; Androgens; Androstenedione; Dehydroepiandrosterone; Female; Gonadal Steroid Hormones; Humans; Libido; Middle Aged; Ovary; Prospective Studies; Rectal Neoplasms; Testosterone
PubMed: 30277569
DOI: 10.1002/bjs.10980 -
Translational Psychiatry Feb 2021Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and...
Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27-1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.
Topics: Adolescent; Adult; Aged; Androgens; Androstenedione; Depression; Depressive Disorder, Major; Female; Humans; Middle Aged; Sex Hormone-Binding Globulin; Testosterone; Young Adult
PubMed: 33579903
DOI: 10.1038/s41398-021-01249-2 -
Reproductive Biology and Endocrinology... Jun 2022According to current definitions of Polycystic Ovary Syndrome (PCOS), hyperandrogenism is considered as a key element in the pathogenesis of this common endocrinopathy....
BACKGROUND
According to current definitions of Polycystic Ovary Syndrome (PCOS), hyperandrogenism is considered as a key element in the pathogenesis of this common endocrinopathy. However, until now, studies about ovarian androgen profile in women are very rare. Our aim was then to characterise the expression profile of the androgens in follicular fluid of 30 PCOS patients, and compare it to those of 47 Control women and 29 women with only polycystic ovary morphology on ultrasounds (ECHO group).
METHODS
A retrospective, single-centre cohort study was performed. The intrafollicular concentrations of the key androgens were assessed and correlated with the intrafollicular levels of some adipokines of interest. Androgens were quantified by mass spectrophotometry combined with ultra-high-performance liquid chromatography, while adipokine concentrations were measured by ELISA assays.
RESULTS
In PCOS patients, the intrafollicular concentrations of the androgens synthesised by ovarian theca cells, i.e., 17OH-pregnenolone, dehydroepiandrosterone, Δ4-androstenedione and testosterone, were significantly higher than those of the androgens of adrenal origin, and positively correlated with the main PCOS clinical and biological features, as well as with the adipokines mostly expressed in the follicular fluid of PCOS patients, i.e. resistin, omentin, chemerin and apelin. Conversely, Control women showed the highest levels of 17OH-progesterone, deoxycorticosterone and 11-deoxycortisol. Confirming these results, apelin levels were negatively associated with pregnenolone and deoxycorticosterone concentrations, while visfatin levels, which were higher in the Control group, negatively correlated with the Δ4-androstenedione and testosterone ones.
CONCLUSIONS
PCOS is characterised by a selective increase in the intrafollicular levels of the androgens synthesised by theca cells, strengthening the hypothesis that ovarian hyperandrogenism plays a central role in its pathogenesis. Further, the significant correlation between the intrafollicular concentrations of the androgens and most of the adipokines of interest, including apelin, chemerin, resistin and omentin, confirms the existence of a close relationship between these two hormonal systems, which appear deeply involved in ovarian physiology and PCOS physiopathology.
Topics: Adipokines; Androgens; Androstenedione; Apelin; Cohort Studies; Desoxycorticosterone; Female; Follicular Fluid; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Pregnenolone; Resistin; Retrospective Studies; Testosterone
PubMed: 35701786
DOI: 10.1186/s12958-022-00959-6 -
Food and Chemical Toxicology : An... Sep 2011Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and...
Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (2-year) exposure by gavage at 10, 20, or 50 mg/kg in rats and male mice, and 2, 10, or 50 mg/kg in female mice (50 mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar adenoma and carcinoma occurred in the 20 mg/kg male rats and increases in mononuclear cell leukemia occurred in the 20 and 50 mg/kg female rats, which may have been related to androstenedione administration. In male and female mice, androstenedione was carcinogenic based upon a significant increase in hepatocellular tumors. A marginal increase in pancreatic islet cell adenomas in male (50 mg/kg) and female (2, 10, 50 mg/kg) mice was considered to be related to androstenedione administration. Interestingly, incidences of male rat Leydig cell adenomas and female rat mammary gland fibroadenomas decreased. In conclusion, androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.
Topics: Androstenedione; Animals; Carcinogenicity Tests; Carcinogens; Dose-Response Relationship, Drug; Female; Male; Mice; Rats; Rats, Inbred F344
PubMed: 21651954
DOI: 10.1016/j.fct.2011.05.026 -
PloS One 2023Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands...
Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands (e.g. gonads), the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in regions involved in the regulation of social behaviors and may act locally to regulate social behaviors, such as reproduction and aggression. Our model species, the weakly electric fish Gymnotus omarorum, displays non-breeding aggression in both sexes. This is a valuable natural behavior to understand neuroendocrine mechanisms that differ from those underlying breeding aggression. In the non-breeding season, circulating sex steroid levels are low, which facilitates the study of neurosteroids. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain to characterize steroid profiles in wild non-breeding adult males and females. We show that: 1) systemic steroid levels in the non-breeding season are similar in both sexes, although only males have detectable circulating 11-ketotestosterone, 2) brain steroid levels are sexually dimorphic, as females display higher levels of androstenedione, testosterone and estrone, and only males had detectable 11-ketotestosterone, 3) systemic androgens such as androstenedione and testosterone in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data are consistent with previous studies of G. omarorum that show non-breeding aggression is dependent on estrogen signaling, as has also been shown in bird and mammal models. Overall, our results provide a foundation for understanding the role of neurosteroids, the interplay between central and peripheral steroids and potential sex differences in the regulation of social behaviors.
Topics: Animals; Female; Male; Electric Fish; Androstenedione; Neurosteroids; Chromatography, Liquid; Tandem Mass Spectrometry; Aggression; Gonadal Steroid Hormones; Testosterone; Steroids; Estrogens; Brain; Seasons; Mammals
PubMed: 37816021
DOI: 10.1371/journal.pone.0289461 -
The Journal of Clinical Endocrinology... Nov 2023Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in...
CONTEXT
Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations.
OBJECTIVE
To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children.
METHODS
We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs.
RESULTS
The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin.
CONCLUSION
A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Puberty; Testosterone; Exercise; Diet, Healthy
PubMed: 37329220
DOI: 10.1210/clinem/dgad367