Female adolescents have a greatly increased risk of depression starting at puberty, which continues throughout the reproductive lifespan. Sex hormone fluctuation has been highlighted as a key proximal precipitating factor in the development of mood disorders tied to reproductive events; however, hormone-induced affective state change is poorly understood in the pubertal transition. The present study investigated the impact of recent stressful life events on the relationship between sex hormone change and affective symptoms in peripubertal female participants. Thirty-five peripubertal participants (ages 11–14, premenarchal, or within 1 year of menarche) completed an assessment of stressful life events, and provided weekly salivary hormone collections [estrone, testosterone, dehydroepiandrosterone (DHEA)] and mood assessments for 8 weeks. Linear mixed models tested whether stressful life events provided a context in which within-person changes in hormones predicted weekly affective symptoms. Results indicated that exposure to stressful life events proximal to the pubertal transition influenced the directional effects of hormone change on affective symptoms. Specifically, greater affective symptoms were associated with increases in hormones in a high stress context and decreases in hormones in a low stress context. These findings provide support for stress-related hormone sensitivity as a diathesis for precipitating affective symptoms in the presence of pronounced peripubertal hormone flux.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases characterised by unusual levels of sex hormones and dysfunction of the ovaries. The infertility rate is high among patients with PCOS. Unusual hormonal status can lead to the inability of ovaries to release functional and mature follicles. Clinical trials on the effects of N-acetylcysteine (NAC) supplementation on ovulation and sex hormones profile in women with PCOS have been controversial. We performed a systematic review and meta-analysis to evaluate the potential effects of NAC supplementation on ovulation and sex hormones profile. PubMed, Scopus, Embase, Web of Science and Cochrane Central library international databases were searched till September 2021. Meta-analysis was performed using a random-effects approach in case of significant between-study heterogeneity. Eighteen studies, including 2185 participants, were included in the present meta-analysis. NAC significantly reduced total testosterone (TT) levels (standardised mean difference (SMD): −0·25 ng/ml; 95 % CI (−0·39, −0·10); ‘P < 0·001’, I 2 = 53·9 %, P = 0·034) and increased follicle-stimulating hormone (FSH) levels (SMD: 0·39 mg/ml; 95 % CI (0·07, 0·71); P = 0·01, I 2 = 70·9 %, P = 0·002). Oestrogen levels also increased after correcting publication bias. However, no significant effect was observed on the number of follicles, endometrial thickness, progesterone, serum luteinising hormone levels and sex hormone-binding globulin. The results indicated that NAC supplementation decreased TT levels and increased FSH levels. Overall, NAC supplementation might be effective in the improvement of reproductive system function in patients with PCOS.

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality – both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.

The objective was to investigate associations between life-course adiposity and sex hormone concentrations: trajectory of adiposity from age 5 to 40 (premenopausal)/60 (postmenopausal women and men) in relation to levels of oestrone (E1), oestradiol (E2), sex hormone-binding globulins (SHBG), testosterone in 4801 premenopausal and 6019 postmenopausal women in the Nurses’ Health Study (NHS) and NHS II, and 2431 men in the Health Professionals Follow-up Study. We used group-based trajectory models to identify groups within each cohort based on recalled somatotypes and reported BMI. Multivariate linear regression models were used to compare sex hormone concentration across different trajectory groups. The mean age at blood draw was 64·1 ± 8·1 years for men, 59·4 ± 6·0 for postmenopausal and 44·1 ± 4·6 for premenopausal women. In men, compared with the medium-stable group, lean-marked increase and medium increase groups had lower levels of SHBG (percentage difference: −17 and −9 %) and testosterone (−15 and −13 %). In postmenopausal women, compared with the medium-stable group, lean-marked increase and medium increase groups had higher levels of E1 (21 and 34 %) and E2 (45 and 68 %) but lower level of SHBG (–29 and −35 %). In premenopausal women, compared with the lean-moderate increase group, medium-stable/increase and heavy-stable/increase groups had lower levels of SHBG (–6 and −28 %). Attained adulthood adiposity and middle-life weight gain were associated with lower SHBG and testosterone in men, higher E1 and E2 and lower SHBG in postmenopausal women, and lower SHBG in premenopausal women. The study indicates the importance of maintaining a healthy body weight throughout life course for homoeostasis of sex hormones.

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

The present study investigated dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS). A total of forty-five women (aged 25–40 years) with PCOS and 161 control women (aged 25–43 years) with non-PCOS-related infertility were recruited. Anthropometry, glucose tolerance and sex hormones were determined and dietary intake was assessed. Women with PCOS had lower serum sex hormone-binding globulin and increased BMI, waist:hip ratio, luteinising hormone, ratio of luteinising hormone:follicle-stimulating hormone, testosterone and free androgen index (FAI). Postprandial glucose, fasting insulin and insulin resistance were elevated in women with PCOS. Women with PCOS had reduced energy and carbohydrate intake but higher fat intake. Serum sex hormone-binding globulin level was negatively associated with BMI in both groups and negatively correlated with macronutrient intake in the PCOS group with hyperandrogenism. However, FAI was positively correlated with BMI, waist circumference and glucose metabolic parameters in both groups. Therefore, women with PCOS consume lower energy and carbohydrate compared with those with non-PCOS-related infertility and macronutrient intake is only negatively associated with serum sex hormone-binding globulin level in the PCOS group with hyperandrogenism.

Objective: Complications of pelvic irradiation for rectal cancer have gained more attention because of increased survival of patients. The aim of this study was to compare testes doses when pelvis is irradiated using Cobalt 60 (Co60) for rectal cancer in comparison with linear accelerator (LINAC) and its effect on sex hormones levels.

Materials and Methods: In a cohort study, 28 rectal cancer patients that were candidate to receive pelvic radiotherapy were recruited in the study consecutively. They were sequentially assigned to receive radiotherapy using Co60 teletherapy or LINAC. Serum sex hormones levels were measured before and 3–6 weeks after irradiation. Testes absorption doses were measured three times during whole course of irradiation in nine patients.

Results: Testes doses in LINAC group were significantly lower than Co60 group (p < 0.001). Serum follicular-stimulating hormone (FSH) and luteinising hormone (LH ) levels increased after irradiation in both groups and there was not a significant relation between FSH and LH levels with treatment machine (p < 0.2 and p < 0.6, respectively). Serum testosterone level decreased significantly in Co60 group (p < 0.05) but not in LINAC group (p < 0.3).

Discussion: It seems using LINAC for pelvic irradiation in patient with rectal cancer cannot prevent hormonal changes and we suggest using extra shield to decrease testes doses below the toxic levels.

The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15·2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.

This study describes the effects of testosterone (Te) on the intestinal nematode Heterakis spumosa in mice. The course of Heterakis infections is apparently under Te-control. At high circulating Te-levels as occurring in intact males, Te-treated females, and Te-treated castrated males, the period of release of Heterakis eggs in mouse faeces is greatly extended and the number of eggs released per unit time is markedly elevated in comparison to low Te-levels, as found in untreated females and castrated male mice. Also, the onset of the patent period occurs earlier in Te-treated mice. Testosterone also accelerates development and growth of both female and male worms of Heterakis in mice. Thus, young adult male worms can be observed in the upper colon of Te-treated castrated male mice on day 21 post-infection (p. i.), whereas, at that time, only L4 larvae are present in Te-untreated male castrates. Testosterone also favours the survival of nematodes in hosts. In untreated male castrates, the number of worms present on day 7 p.i. (L2 larvae) is approximately two thirds higher than that found on day 21 p.i. However, such a reduction in the number of worms does not occur in Te-treated castrated mice during the same period of time. The early phases of the life-cycle of Heterakis, i.e. hatching in the small intestine and final settling of L2 larvae in the upper colon are independent of Te. Also, Te does not affect motility and even slightly reduces the fecundity of adult female worms in vitro. Our data suggest that Te and/or Te-metabolites and/or Te-induced host factor(s) accelerate the development and growth of H. spumosa and favour the survival of Heterakis in the colon of mice.

Mast cells of connective tissue type are scattered in the interstitial compartment of the lizard Podarcis s. sicula. Their number varies during the year, showing peaks in spring and in winter, respectively.Thermal manipulation affects mast cell number (MCN): high temperature decreased MCN in both January and May, while low temperature increased MCN only in January. Ethane dimethane sulphonate, a toxin which specifically destroys Leydig cells, induced an increase in MCN on days 3 and 7 of treatment. Oestradiol treatment provoked a strong increase in MCN that was blocked by tamoxifen. Blocking androgen receptors with cyproterone acetate resulted in an increase in MCN, while testosterone injection provoked a strong decrease. These results suggest a relationship between the presence of mature Leydig cells and mast cell proliferation and/or differentiation.

There is considerable epidemiological evidence that a Western-style diet may increase the risk of certain hormone-dependent conditions in men via its effects on hormone metabolism. Experimental evidence also suggests that dietary factors may exert subtle effects on hormone metabolism. Here we review the clinical and epidemiological evidence that diet is associated with circulating sex hormone levels in men. In comparison with factors such as age and BMI, nutrients do not appear to be strong determinants of sex hormone levels. Dietary intervention studies have not shown that a change in dietary fat and/or dietary fibre intake is associated with changes in circulating sex hormone concentrations over the short term. The data on the effects of dietary phyto-oestrogens on sex hormone levels in men are too limited for conclusions to be drawn. Observational studies between men from different dietary groups have shown that a vegan diet is associated with small but significant increases in sex-hormone-binding globulin and testosterone concentrations in comparison with meat-eaters. However, these studies have not demonstrated that variations in dietary composition have any long-term important effects on circulating bioavailable sex hormone levels in men. This lack of effect may be partly explained by the body's negative feedback mechanism, which balances out small changes in androgen metabolism in order to maintain a constant level of circulating bioavailable androgens. It appears, therefore, that future studies should look for dietary effects on the feedback mechanism itself, or on the metabolism of androgens within the target tissues.

Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer, but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.

Glial−neuronal interactions are crucial processes in neuromodulation and synaptic plasticity. The neuregulin 1 family of growth and differentiation factors have been implicated as bidirectional signaling molecules that are involved in mediating some of these interactions. We have shown previously that neuregulin 1 expression is regulated by the gonadal hormones progesterone and 17β-estradiol in the CNS, which might represent a novel, indirect mechanism of the neuromodulatory actions of these gonadal hormones. In the present study, we sought to determine the effects of progesterone and 17β-estradiol on neuregulin 1 expression in rat cortical astrocytes and neurons in vitro. We observed that progesterone increased the expression of neuregulin 1 mRNA and protein in a dose-dependent manner in cultured astrocytes, which was blocked by the progesterone receptor antagonist RU-486. In contrast, 17β-estradiol did not increase either neuregulin 1 mRNA or protein in astrocytes. We observed no effect of either progesterone or 17β-estradiol on neuregulin 1 mRNA and protein in rat cortical neurons in vitro. Finally, we observed that treatment of cortical neurons with recombinant NRG1-β1 caused PSD-95 to localize in puncta similar to that observed following treatment with astrocyte-conditioned medium. These results demonstrate that progesterone regulates neuregulin 1 expression, principally in astrocytes. This might represent a novel mechanism of progesterone-mediated modulation of neurotransmission through the regulation of astrocyte-derived neuregulin 1.

The objective of the present study was to assess the effect of consumption of a yoghurt-based drink enriched with 1–2 g plant sterols/d on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolaemia. Thirty patients were randomly assigned to one of two treatment groups: a low-fat low-lactose yoghurt-based drink enriched with 1 g plant sterol extracted from soyabean/d v. a low-fat low-lactose yoghurt, for a period of 4 weeks. After a 2-week wash-out period, patients were crossed over for an additional 4-week period. Second, after a 4-week wash-out period, eleven patients were treated with 2 g plant sterols/d in a second open part of the study for a period of 8 weeks. The yoghurt enriched with plant sterols significantly reduced, in a dose-dependent manner, serum total cholesterol and LDL-cholesterol levels and LDL-cholesterol:HDL-cholesterol (P<0·001), whereas no changes were observed in HDL-cholesterol and triacylglycerol levels, either in the first or the second part of the study. There were only slight, not statistically significant, differences in serum transaminase, vitamin and hormone levels. To conclude, a low-fat yoghurt-based drink moderately enriched with plant sterols may lower total cholesterol and LDL-cholesterol effectively in patients with primary moderate hypercholesterolaemia.

This study confirms our previous data on the effects of sex hormones on mast cell number (MCN) in the testis of frog Rana esculenta. After 15 days of treatment with oestradiol (E2) MCN strongly increases, while testosterone has no effect. After 30 days only a small increase in MCN is observed. These differences could be due to the non-physiological effect of E2 over a prolonged period. We also confirmed a massive increase in MCN after 15 or 30 days of treatment with cyproterone acetate (CPA). This increase in MCN is also observed after administration of CPA with tamoxifen. Ultrastructural analysis of testis shows empty spaces with degenerating Leydig cells in the interstitial compartment and numerous germinal cells completely degenerated, probably apoptotic, in the adjacent germinal compartment. The same effects were observed in testes after treatment with only CPA. Chronic E2 treatment provokes an increase in MCN on day 2. From day 4 to 12 of the treatment, MCN decreases dramatically and many germinal tubules appear strongly disorganised. In conclusion, the present results confirm that E2 treatment induces changes in MCN and chronic E2 treatment modifies the morphology of the frog testes. In addition, blocking androgen receptors with CPA, alone or in combination with tamoxifen, causes a significant increase in MCN, confirming the involvement of androgens in mast cell proliferation and/or differentiation.