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Sex hormone binding globulin binding capacity, testosterone, 5alpha-dihydrotestosterone, oestradiol and prolactin in plasma of patients with prostatic carcinoma under various types of hormonal treatment.

Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5alpha-dihydrotestosterone (DHT), of oestradiol-17beta (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (%TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15% of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with 1) Antiandrogen (cyproterone acetate, Androcur) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n=5. 2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n=32. 3) Cyproterone acetate after orchidectomy led to elevated hPr values. n=5. 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6. 5) Corticosteroid (Prednisone, Decortin) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone. n=5. 6) Diureticum (Mefruside, Baycaron) (n=5) or 7) a placebo (n=7) did not alter any of the parameters measured. 8) Treatment with HCG (Primogonyl) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased. n=7.

Chorionic Gonadotropin

Sex hormones correlated with sex skin swelling and rectal temperature during the menstrual cycle of the pigtail macaque (Macaca nemestrina).

Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction.

Animals

Regulation of the expression of autoimmunity in NZB x NZW F1 mice by sex hormones.

This study examines the role of sex hormones in modulating the expression of autoimmunity in NZB x NZW F1 mice. Male sex hormones were found to retard disease. Differences were noted between prepubertally and postpubertally altered males and females. The presence of male sex hormones prepubertally was associated with marked retardation of the development of antibodies to DNA. Prepubertal but not postpubertal castration of males led to significant acceleration in anti-DNA production. Nevertheless, administration of male sex hormones to females retarded the development of fatal glomerulonephritis, even when given postpubertally. These results suggest that manipulation of sex hormones may be used to modify the expression of autoimmunity.

Animals

Amino acid profiles, aging, and sex hormone interactions in the elderly Iranian population: a metabolomics study.

BACKGROUND: Aging and sex hormones significantly influences on metabolic profiles, particularly in individuals aged 50 year and older. This study aimed to investigate the associations between serum metabolites, aging, and sex hormone levels among elderly individuals in Bushehr, Iran - a coastal region characterized by a unique lifestyle, dietary patterns, and environmental conditions, such as high seafood consumption and exposure to marine climate, which may collectively influence metabolic profiles and hormone levels in the aging population. METHODS: This cross-sectional study analyzed data from the Bushehr Elderly Health Program, which included 2001 participants (1143 women and 858 men) aged over 50 years old from Bushehr, Iran. Serum levels of 20 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the results were analyzed based on gender, age, menopause status, menopause age, and serum levels of sex hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2). Statistical analyses were performed using SPSS version 25.0 and R version 4.0.3, with a focus on gender differences and the correlation between aging, sex hormones, and metabolite profiles. RESULTS: Among the 2001 participants, mean ages were 61.57 ± 7.6 years for women and 62.92 ± 8.4 years for men. Men had higher serum levels of glutamic acid, leucine, methionine, phenylalanine, tyrosine, valine, citrulline, ornithine, proline, threonine, histidine, lysine, tryptophan, asparagine, and glutamine, while women had higher levels of glycine and serine. Aging was associated with notable changes in amino acid levels, such as increased citrulline and decreased threonine in women, and similar trends in men with a pronounced decrease in alanine. In men, low testosterone levels were linked to reduced concentration of alanine, methionine, phenylalanine, tyrosine, citrulline, glycine ornithine, serine, lysine, asparagine, and glutamine. Postmenopausal women showed a significant decrease in threonine levels. DISCUSSION: The findings highlight the complex interplay between aging, sex hormones, and metabolic changes. Gender-specific differences in amino acid profiles suggest that sex hormones play a pivotal role in modulating metabolism, which may influence susceptibility to metabolic disorders. These insights could inform the development of targeted interventions tailored to the specific needs of aging populations. Future research should investigate the underlying mechanisms linking sex hormones to metabolic pathways and assess their potential for improving health outcomes in older adults.

Aging

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

BACKGROUND: Sex bias is pervasive in tumors; however, how sex chromosomes and hormone-responsive signaling shape the tumor microenvironment (TME) remains insufficiently characterized. Considering the critical impact of the TME on tumor progression and response to immunotherapy, a pan-cancer investigation of sex-specific and cancer-context-dependent TME features is warranted. METHOD: Based on stringent inclusion criteria, we constructed a high-resolution pan-cancer single-cell sequencing atlas by integrating 31 publicly available single-cell RNA-seq datasets, comprising a total of 1,831,436 cells by integrating 468 samples from eight types of non-sex-specific solid tumors (282 males and 186 females). After correcting for batch effects, we identified major and minor cellular subsets. Multiple computational approaches were applied to investigate sex-associated differences in cellular composition, gene expression, pathway activity, malignant cell states and intercellular communication. RESULTS: We systematically compared sex-specific TME features across eight common solid malignancies. Male-biased CD8+ T cell exhaustion emerged as a recurrent but non-uniform feature, with its magnitude varying across cancer types and being modified by tissue-specific contexts. This pattern was associated with androgen-response signature scores and expression-based loss of the Y chromosome (LOY) scores. M2-like macrophage polarization showed a more cancer-type-dependent pattern; although female-biased enrichment was observed in selected malignancies, it did not represent a uniform pan-cancer feature. Expression-based X chromosome inactivation (XCI)/XCI escape-related programs, estrogen-response signature scores and stromal components, including fibroblasts and endothelial cells, were associated with macrophage and immune-regulatory states in specific tumor contexts. Tumor cells of male origin displayed higher genomic instability and more aggressive phenotypes, with androgen-response signatures and LOY contributing to the development of a male biased malignant state. Furthermore, expression-based LOY scores in malignant cells were associated with CD8+ T cell exhaustion based on transcriptomic proxies. CONCLUSION: Our study uncovers extensive but heterogeneous sex-specific differences in the TME across multiple cancer types. We propose a regulatory framework linking sex chromosomes, hormone-responsive signaling and TME interactions, which is consistent with recurrent male-biased CD8⁺ T cell exhaustion and context-dependent M2-like macrophage polarization. Importantly, the magnitude and, in some cancers, the direction of these sex-biased features are modified by tissue-specific contexts. These findings underscore the need to include sex chromosome and hormone status as essential biological variables in studies of the tumor microenvironment and the design of immunotherapies.

Tumor Microenvironment

Sex hormone binding globulin capacity and postmenopausal hormone replacement therapy.

The sex hormone binding globulin (SHBG) capacity was measured in 26 normal untreated postmenopausal women and 10 postmenopausal women taking different types of hormone replacement therapy. The patients on hormone replacement therapy had significantly higher levels of SHBG than postmenopausal women (p less than 0.001) and also significantly higher levels than 52 normal ovulating women studied previously (Pogmore and Jequier, 1979; p less than 0.02). This suggests that postmenopausal women on hormone therapy are being overtreated.

Adolescent

Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy.

OBJECTIVE: To assess the alterations of endogenous sex hormone profiles in patients with epilepsy (PWE) on different antiepileptic drug (AED) monotherapies compared to healthy controls and drug naïve PWE (DNPWE). METHODS: Four databases MEDLINE, EMBASE, SCOPUS, and CENTRAL were searched for analytical observational/intervention studies on the assessment of endogenous sex hormones in PWE compared to healthy controls and DNPWE. Two researchers reviewed the title/abstract, and full-text articles for the selection of the studies independently. Extracted data included information on study details, participant demographics, interventions, method of assessment and study results. The study outcomes were used to calculate the standard mean differences (SMD) and 95% confidence interval (CI) as effect size for assessing differences in the endogenous sex hormone levels between the treatment group and control/DNPWE. RESULTS: Among 5888 publications retrieved, 33 studies were included. Enzyme-inducing AEDs (EIAEDs) such as phenytoin (men: SMD = 1.36; 95%CI = 1.06,1.66) and carbamazepine (men: SMD = 0.71; 95%CI = 0.39, 1.04 and women: SMD = 0.54; 95%CI = 0.25, 0.83) and weak-EIAED oxcarbazepine (men: SMD = 0.62; 95%CI = 0.26,0.99) increased the SHBG levels in PWE compared to control. The same trend was observed when comparing it to DNPWE. No significant changes in SHBG were observed for non-EIAEDs valproic acid, lamotrigine and levetiracetam in men. Lamotrigine significantly reduced SHBG in women (SMD = -0.50; 95%CI = -0.85, -0.16) compared to controls. Testosterone (T) levels were significantly reduced for both carbamazepine (SMD = -0.39; 95%CI = -0.67, -0.11) and valproic acid (SMD = -0.48; 95%CI = -0.74, -0.21) treated men compared to control. SIGNIFICANCE: Our findings emphasize the importance of screening the endogenous sex hormonal profile in PWE on AED monotherapies to evaluate the associated endocrine-related perturbations which may impact reproductive functions.

Humans

Sex hormone binding globulin: the carrier protein for d-norgestrel.

The binding of different synthetic steroids, used in hormonal contraception, to Sex Hormone Binding Globulin (SHBG) was studied by measuring their ability to displace tritiated testosterone from SHBG in a competitive protein binding system. Only 19-nortestosterone derivates had any significant ability to displace testosterone from SHBG, d-norgestrel (d-Ng) being the strongest displacer. Increasing the SHBG levels in women with previous constant plasma d-Ng levels increased these levels two- to sixfold. It is concluded that SHBG is the main carrier protein for d-Ng. The strong testosterone displacing activity of d-Ng might also explain androgenic side effects observed with d-Ng containig oral contraceptives.

Acne Vulgaris

Sex Hormone Receptors, HBV Integrations and Their Prognostic Predictive Value Among Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection predominantly affects males, yet few studies have investigated the association between sex hormones and HBV integrations, and their involvement in HCC prognosis. We assessed estrogen receptor alpha (ERα) and androgen receptor (AR) expression via immunohistochemistry on tissue microarrays constructed from 426 HBV-related HCC samples. HBV integration features were determined using HBV-captured sequencing data. Logistic regression models were utilized to evaluate the association between sex hormone receptor expression level and HBV integration features. Cox regression models, combined with machine learning (ML) methods, were implemented to investigate the prognostic value of sex hormone receptors and HBV integrations concerning overall survival. We found high AR expression level was significantly associated with higher HBV integration levels (adjusted odds ratio [aOR] = 1.84, 95% confidence interval [CI]: 1.09-3.11, P for trend = 0.012), TERT integration (aOR = 2.34, 95% CI: 1.16-4.74, P for trend = 0.047), intergenic integration (aOR = 2.25, 95% CI: 1.20-4.24, P for trend = 0.021), and promoter integration (aOR = 1.81, 95% CI: 1.00-3.31, P for trend = 0.034). The inclusion of sex hormone receptors and HBV integrations in the predictive models led to improvements across all performance metrics in the Cox regression analyses (AUC improvement: 0.014 [Training], 0.026 [Validation]) and the ML (AUC improvement: 0.022 [Training]), although a slight deterioration in performance was noted in the ML validation set. The results suggested a relationship between AR expression level and HBV integration events, as well as the potential utility of HBV integration biomarkers and sex hormone receptor profiles in assessing post-surgical prognosis among HCC patients.

Humans

Postmenopausal osteoporosis: the effect of parathormone and large dose vitamin D3 on the serum calcium level in sex hormone deficient rats.

Rats deprived of adrenal and gonadel sex hormones are more sensitive than normal rats to the hypercalcaemic (osteolytic) effect of parathormone and toxic doses of vitamin D3. It is suggested that sex hormone deficiency and the consecutive decrease of calcitonin sensitivity in postmenopausal osteoporosis makes the patients unprotected against factors inducing increased bone resorption, and this leads over the years of osteoporosis.

Adrenalectomy

[Male sex hormones and their derivatives. Pathophysiology and therapy].

After a short review of the chemistry, biosynthesis and physiology (regulation of production and secretion, effects) of the male sex hormones, the possible disturbances of the male sex hormones, the possible disturbances of the male sex function are pathophysiologically listed and some instructive diseases, as castration, testicular feminization, Kallmann syndrome, prolactinoma and flour-bag-drawfs, are discussed. Regarding the main topic, influence of general diseases on sex hormones, the implications of the cirrhosis of the liver and the dialysis in kidney disease are listed as examples. Indications and particularly the contraindications and dangers of testosterone and anabolic steroid therapy are discussed.

Adrenal Cortex

Effect of infusion of gonadotropin releasing hormone upon plasma concentrations of sex hormones in prepubertal and pubertal males.

Plasma testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17OHP), androstenedione (A), estradiol (E2), and dehydroepiandrosterone sulfate (DHAS) were measured by radioimmunoassay after celite chromatography prior to and after a 3-hour infusion of the synthetic gonadotropin releasing factor, GnRH, in normal prepubertal and pubertal boys. Plasma T levels rose (p less than 0.001) in the pubertal but not prepubertal boys. 17OHP concentrations increased in those boys who had an increment of T. A, DHT, E2 or DHAS levels did not increase after GnRH. Basal levels of T, DHT, A and DHAS correlated with the peak and mean serum LH levels attained during the GnRH infusion. These data confirm the greater Leydig cell responsivity to transient rises of endogenous gonadotropin in pubertal males and also suggest that there may be a relationship between adrenal androgen production and maturation of the hypothalamic-pituitary-gonadal system.

Age Factors

Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin.

The renal clearance of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of the semisynthetic penicillin, cyclacillin, is about 10 times faster in female than in male rats. The slower clearance in males is attributed to a higher net rate of reabsorption of the compound from the tubule of the kidney. Because ACHC is not metabolized, it is apparently continuously recirculated through the kidney of the male, resulting in the longer half-life. The sex-related disposition of the metabolite can be modified by gonadectomy and/or treatment with sex hormones. Castrated males show increased urinary excretion and decreased plasma half-life of ACHC relative to intact males. In ovariectomized females, less ACHC is excreted and the half-life is longer than in intact females. Thus, in both sexes, gonadectomy shifts the excretion and the residence time in plasma toward the values of these parameters for the opposite sex. Treatment of castrated males with estradiol markedly enhances the effect of castration, but treatment of ovariectomized females with testosterone propionate has little or no additional effect over ovariectomy. Treatment of intact males with estradiol modifies both excretion and residence time in plasma to a great extent, but treatment of intact females with testosterone has a lesser effect on the disposition of ACHC. These results indicate that excretion and residence time of ACHC in both male and female rats are influenced by sex hormones. The described effect is an example of the action of sex hormones on the transport of foreign compounds in this species. Its mechanism is quite different from the well known influence of sex hormones on the microsomal metabolism of foreign compounds in rats.

Animals

[Sex hormone excretion in stomach cancer patients].

Study on the balance of sex hormones in 43 males and 45 females with gastric cancer indicated the presence of some deviations from normal level of androgens and estrogens excretion in gastric cancer patients. The character and intensity of the deviations observed were dependent on patients' sex and stage of the disease. In males the leading factor in sex hormones excretion disorders is a regular decrease both of 17-KS and estrogens, and only in stage UV hyperestrogenization phenomena are observed on account of active estrogens being predominant over androsterone. In females relative hyperestrogenization was observed already in stage III on acount of androsterone decrease, while in stage IV--due to reduction of total 17-KS in normal level of total enstrogens.

11-Hydroxycorticosteroids

Sex hormones and tyrosine hydroxylase activity in vascular and adrenal tissue.

Vascular tyrosine hydroxylase (TH) activity did not appear to be affected by the sex hormones. There were no differences in enzyme activity in the mesenteric artery or vein taken from male and female normotensive or spontaneously hypertensive rats. Castration of either male or female rats did not alter mesenteric artery or vein TH activity, and the administration of estradiol, progesterone, or testosterone also had no effect on vascular TH activity. However, the sex hormones did alter activity in other tissues. Estradiol and progesterone administration to intact female rats increased adrenal TH activity, whereas castration of the male rat decreased it. Although the sex hormones were not important regulators of TH in blood vessels, vascular TH activity did appear to be under some hormonal regulation since hypophysectomy decreased mesenteric artery enzyme activity. Hypophysectomy studies also indicated that adrenal TH activity was under some hormonal regulation.

Adrenal Glands

Evaluation of the gut microbiome and sex hormones in postmenopausal women with newly diagnosed hormone receptor-positive breast cancer versus healthy women: a prospective case-control study.

PURPOSE: The functional composition and diversity of the gut microbiome may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investigated the relationship between the gut bacterial microbiome and endogenous estrogens and related sex hormones in women with hormone receptor-positive breast cancer compared to healthy control women. The goal was to determine if the estrobolome (i.e., bacteria capable of modulating the body's circulated estrogen levels) was altered in those with breast cancer compared with controls. METHODS: In this prospective case-control study, postmenopausal women (n = 46) with newly diagnosed stage I-III estrogen and/or progesterone receptor-positive breast cancer were compared with healthy postmenopausal female controls (n = 22). Bacterial composition of the gut microbiome was analyzed by 16S rRNA gene sequencing from fecal specimens. Plasma and urine sex hormones were quantified using high-performance liquid chromatography/mass spectrometry. RESULTS: We found evidence that some β-glucuronidase positive bacteria were enriched in the breast cancer patients compared to healthy controls, whereas abundances of some β-glucuronidase negative bacteria were reduced. There was also a wide distribution of prevalence of β-glucuronidase positive taxa in both breast cancer subjects and healthy controls, as well as higher probability of breast cancer subjects having higher average β-glucuronidase levels. Significant differences were found in endogenous progesterone levels between the breast cancer patients and healthy controls. CONCLUSION: This pilot study showed differences in the gut microbiome and endogenous progesterone levels among postmenopausal women with hormone receptor-positive breast cancer compared with healthy controls. These interesting findings may have implications for breast cancer risk and prevention and warrant further exploration.

Humans

[Sex hormones and depth of voice in the male (author's transl)].

Correlations between sex hormone levels and the male depth of voice were investigated in 102 singers. As compared to tenor singers higher testosterone and lower oestradiol plasma concentrations were measured in bass and baritone singers. This resulted in higher testosterone/oestradiol ratios due to increased androgens in those with deeper voices. Deeper voices were associated with taller and heavier body build. In the young age group sexual activity was highest among the bass voices, in the middle and old age group tenors were most active. There were no depth of voice-related differences as regards the sequence and occurrence of different pubertal characteristics. Only future bass singers had an increased of acne. The results indicate that the different depths of the male voice are influenced by different concentrations of circulating sex hormones and also by the androgen sensitivity of the target organs.

Acne Vulgaris