Female Estrogen Research Articles

Endometrial receptivity in women of reproductive age with "thin" and "absolutely thin" endometrium

Aim. To evaluate the expression of steroid receptors (estrogen [ER] and progesterone [PR]) in the endometrium during the implantation window in females with a history of fertility disorders in "thin" and "absolutely thin" endometrium versus healthy females.
 Materials and methods. A prospective comparative study was conducted. The study group (n=42) included patients with "thin" endometrium (7 mm M-echo 5 mm at cycle days 1113 according to ultrasound); the comparison group (n=10) included females with "absolutely thin" (5 mm according to ultrasound in the pre-ovulatory days) endometrium (females in both groups had a history of infertility and miscarriage of unclear reasons in the anamnesis); the control group included 16 healthy fertile females. A Pipelle biopsy of the uterine mucosa was performed on day 68 after ovulation, and a peripheral blood sample was obtained to measure the concentration of sex steroids (estradiol [E2] and progesterone [P]). Endometrial samples were examined by histological and immunohistochemical methods (ER, PR expression).
 Results. All study participants had an ovulatory cycle of P16.1 nmol/L (day 68 after ovulation) and normal estrogen levels (E2, pmol/L). E2/P was similar in all cohorts (p0.05 for all measures). ER and PR expression in the endometrium similar to those in healthy females was detected in 20% of patients in the study and comparison groups (M-echo = 4.83.1 mm): 21% (9/42) and 20% (2/10), respectively. ER and PR expression in the endometrial glands and ER expression in the endometrial stroma were significantly different (p0.05) from healthy females in 79% (41/52) of patients with "thin" endometrium and 80% (8/10) of patients with "absolutely thin" endometrium. No differences in the ER or PR expression in the endometrium in females with hypoplastic endometrium were found (p0.05).
 Conclusion. The M-echo value does not accurately determine endometrial hormonal-receptor abnormalities: 20% of the study participants with hypoplastic endometrium had ER and PR expression comparable to those in healthy females. No differences were found in the expression of endometrial estrogen and progesterone receptors in females with "thin" and "absolutely thin" endometrium.

Association between age at menarche and bone mineral density in postmenopausal women

BackgroundAge at menarche (AAM) directly affects female estrogen levels, which play a vital role in bone metabolism. The exact relationship between bone mineral density (BMD) and AAM remains controversial. Thus, this study aimed to determine the association between AAM and lumbar spine (LS) BMD in postmenopausal women.MethodsOur data were based on the National Health and Nutrition Examination Survey (NHANES) 2011–2018. AAM was divided into three categories including ≤ 12, 13–15, and ≥ 16 years, and the ≤ 12 years old category was used as the reference group. To examine the association between AAM and LS BMD, we used three weighted linear regression models, Model 1 (without adjustment), Model 2 (with adjustment for age, race, and body mass index [BMI]), and Model 3 (with adjustment for all covariates).ResultsThis study included 1195 postmenopausal women aged 40–59 years. In the unadjusted model, a menarche age of ≥ 16 years compared with a menarche age of ≤ 12 years was associated with lower LS BMD (β = − 0.083, 95% CI − 0.117, − 0.048, P < 0.001). After adjusting for potential confounding factors, there was still a negative correlation in model 2 (β = − 0.078, 95% CI − 0.113, − 0.042, P < 0.001) and model 3 (β = − 0.065, 95% CI − 0.096, − 0.033, P < 0.001). Moreover, this significant relationship persisted after excluding participants who used female hormones (β = − 0.053, 95% CI − 0.089, − 0.016, P = 0.006).ConclusionOur study found that postmenopausal women with a menarche age of ≥ 16 years had significantly lower LS BMD than that had by those with a menarche age of ≤ 12 years. As a result of this study, postmenopausal women with a late menarche age may have a higher risk of lumbar osteoporotic fractures and need better bone health care.

Sex-moderated relationship between the 2D:4D ratio and circulating hormones in an adult Ghanaian population.

The second-to-fourth digit ratio (2D:4D) is the putative marker of prenatal hormone exposure. The 2D:4D ratio or the right-left difference (Dr-l) are said to be negative and positive correlates, respectively, of circulating testosterone and estrogen in both adult males and females. However, previous studies on the subject have reported mixed results. This study aimed to determine the sex-moderated relationship between the 2D:4D ratio and adult circulating testosterone, estradiol, testosterone-to-estradiol ratio and the free androgen index. This was a cross-sectional study from January to June 2021 at the University for Development Studies, Ghana. The study involved 62 participants (Female=28; Male=34), aged between 20 and 26 years. The right (2D:4DR), the left (2D:4DL), and their difference (Dr-l) were measured by computer-assisted analysis. Fasting venous samples were assayed for total testosterone (T), estradiol (E2 ), and sex hormone-binding globulin (SHBG) using ELISA. The free androgen index (FAI) was then calculated (T/SHBG) and the data were analyzed using moderated and/or weighted regression. Males had significantly higher T and FAI than females while females had significantly higher E2 than males, which were independent of age and body mass index (p < 0.001). There was a significant SEX*Dr-l interaction on FAI (p=0.007). The Dr-l correlated negatively with FAI in males but positively in females and accounted for about 94.0% of the variability of FAI in males (adjR2 =0.940) and only 0.2% in females (adjR2 =0.002). The 2D:4D ratio, a putative marker of prenatal hormone exposure, may have an impact on sex differences in adult free androgen index.

Prediction of osteoporosis in men and women through orthopantomograph

Osteoporosis is a systemic disease characterized by low bone mineral density, deterioration of bone structure and increased bone fragility most commonly seen in females of old age as a result of lack of estrogen. The mandibular cortical index, observed on panoramic radiograph, is useful for the screening of osteoporosis. The aim of the study is to study and analyze thickness of mandibular cortical bone on orthopantomography as a representative for the preliminary diagnosis of osteoporosis. The study was conducted on 100 subjects orthopantomographs which included both males and females of all ages. Patients with prior systemic diseases were not included. There were 50% males and 50% females in the age group of 21-90 with 43% in group 1 patients with all teeth, 57% in group 2 patients with few or no teeth. Group 1 had 60.5% males and 39.5% females, Group 2 had 42.1% males and 57.9% females. C1 had 43%, C2 42% and C3 15%. C1 had 52% males, 42% females, C2 had 48% males, 36% females, C3 had 30% females, 0% males. There is relevant relation between age, gender and osteoporosis. With increased age there is decreased oral health seen in both males and females of middle aged. Due to decreased levels of estrogen in females they are more likely to develop osteoporosis. Use of radio morphometric indices on OPG can predict osteoporosis. There are high chances of osteoporosis in females than males.

Level of Estrogen in Females-The Different Impacts at Different Life Stages.

Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis. Thus, ovariectomy impacts the long-term health and lifespan of women. However, the level of estrogen at different life stages should be managed differently. Life quality can be measured in many ways, but mainly it relates to how an individual is doing in terms of being healthy, comfortable, and able to participate in or enjoy life experiences. First of all, ovariectomy not only reduces the level of estrogen but also destroys the reproductive metabolism and potentially other metabolism functions; it may also reduce the lifespan because of the overall impact, not necessary due to the low level of estrogen. Secondly, according to the principal law of the lifespan (PLOSP), the impacts of ovariectomy at different life stages will be different. The objective of this article is to provide readers with a new view of the research on estrogen. Based on the PLOSP, we recapture the estrogen levels at different life stages and explore potential alternative approaches to the manipulation of the levels of estrogen based on the biological features of the difference life stages. Thus, a low level of estrogen in the early life stage may make a woman live longer than a woman with a normal level of estrogen. However, a low estrogen level does not equal ovariectomy. Here, we explain the different impacts of the estrogen levels during different life stages; the effects on the lifespan of the manipulation of estrogen levels at different life stages; and the differences among the estrogen levels, ovariectomy effects, life stages, and lifespan. The personalized manipulation of estrogen levels and relevant growth factors according to the characterization of the life stages may be able to extend the heathy lifespan of women.

Sex-dependent vascular effects of cadmium sub-chronic exposure on rats.

Cadmium exposure is related to several cardiovascular diseases, such as hypertension, atherosclerosis and endothelial dysfunction. However, the toxic effect of cadmium can be dependent on the sex when examined sex in experimental models. The aim of this study was to analyze the effects of cadmium exposure on the cardiovascular system of male and female rodents. The experiments were carried out on both-sexes Wistar at 4months of age, where from 3months onwards, cadmium (CdCl2 100mg/l in placed the drinking water for 30days) or vehicle delivered (distilled water) was ingested. Before and after 30days of exposure to cadmium, systolic blood pressure was regularly measured. After exposure, blood was collected to measure dosage of cadmium, in male and female, and estrogen in females. Vascular reactivity to phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) was studied at respective isolated aortic segments. After the period to Cd-exposure, systolic blood pressure was increased only in the male rats. Males also had higher levels of plasma cadmium than those of female rats, and exposure to the metal did not affect the amount of estrogen produced in the female rats. Increased myeloperoxidase (MPO) activity was also observed in both the males and females that had been exposed to the metal. Moreover, exposure to the cadmium reduced the ACh relaxation and increased vascular reactivity to Phe, resulting in an imbalance between nitric oxide superoxide anion in the isolated aorta of male rats. In female rats, sub-chronic cadmium exposure did not modify the vascular reactivity to Phe and neither to the ACh. The present study revealed that the Cd exposure for 30days induced sex-dependent cardiovascular abnormalities.

The Effects of Ficus carica on Male and Female Reproductive Capabilities in Rats.

The basic purpose of pharmacology is to look into the benefits of natural remedies and make them available to the general populace. Herbal medicines are now considered to be the future of humanity. The current study explored the effects of Ficus carica (FC) extract in rats of two-generation F0 (parents) and F1 (offspring) in either sex. The F. carica extract was initially tested for acute and sub-chronic toxicity. Extracts were also tested for fertility assessment and effects on reproductive hormones like follicle-stimulating hormone (FSH), luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), estradiol, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone-sulfate (DHEAS), insulin, progesterone, and prolactin. The antioxidant activity of the extract was also evaluated by testing mRNA expressions of SOD2, GPX1, CAT, and GR in male testes and female ovaries. The animals treated with 100 mg/kg FC extract produced a more pronounced fertility effect in both genders. Expression of CAT, SOD2, GPX1, and GR was found to be increased in the reproductive organs of both sexes. Histology of the testes reveals increased spermatogenesis and increased folliculogenesis in ovaries. The hormone profile showed an increase in FSH, DHT, estradiol, and DHEAS levels in males and FSH, LH, estrogen, and DHEAS in females. The results of the study establish the effectiveness of natural products in improving fertility issues in either sex.

Sex Difference in Cisplatin-Induced Nephrotoxicity: Laboratory and Clinical Findings.

Cisplatin (CP) as the most important anticancer drug has limited usage due to a lot of side effects such as nephrotoxicity. Additionally, nephrotoxicity is gender/sex-related. There is a variety of experimental studies in association with sex and CP-induced nephrotoxicity. Some studies have reported that female sex is resistant than male sex due to greater antioxidant defense and protective effects of estrogen in females. Other studies have indicated that males are less vulnerable than females due to CP high clearance. Also, various supplementations have revealed conflicting effects in males and females. It is uncovered that sex hormones have determinant roles on the conflicting effects. Some supplements could improve CP-induced nephrotoxicity, but several supplements intensified CP-induced nephrotoxicity, especially in female sex. On the other hand, major clinical studies introduced female gender as a risk factor of CP-induced nephrotoxicity. Although, rare studies evaluated the effect of various supplemental compounds on CP-induced nephrotoxicity in patients underwent CP therapy. Therefore, it requires further investigations to clarify the controversial subject of gender/sex and CP-induced nephrotoxicity in both clinic and laboratory.

Central Feminization of Obese Male Mice Reduces Metabolic Syndrome.

Metabolic syndrome encompasses a spectrum of conditions that increases the risk for cardiovascular and metabolic diseases. It is widely accepted that the sex hormone estrogen plays a protective metabolic role in premenopausal women, in part through central nervous system (CNS) mechanisms. However, most work to date has focused on the loss of estrogen in females (e.g., menopause). Interestingly, transgender individuals receiving feminizing gender affirming therapy (i.e., estrogen) are relatively protected from metabolic syndrome conditions, pointing to a role for CNS estrogen in the development of metabolic syndrome in men. Here, we show that estrogen signaling in the brain protects males from metabolic syndrome and obesity related complications. First, short-term CNS specific supplementation of low-dose 17-β-estradiol in diet-induced obese male mice resulted in a significant reduction in body weight in parallel with a decrease in food intake without alterations in energy expenditure. In conjunction, central supplementation of estrogen reduced visceral adiposity, including epididymal and abdominal regions, with slighter decreases in subcutaneous inguinal and thermogenic brown adipose tissue. Furthermore, central estrogen administration reduced the liver manifestation of metabolic syndrome including hepatomegaly and hepatic steatosis. Collectively, these findings indicate that a lack of estrogen action in the brain may predispose males to metabolic syndrome pathogenesis.

Global phosphoproteomic profiling of skeletal muscle in ovarian hormone-deficient mice.

Protein phosphorylation is important in skeletal muscle development, growth, regeneration, and contractile function. Alterations in the skeletal muscle phosphoproteome due to aging have been reported in males; however, studies in females are lacking. We have demonstrated that estrogen deficiency decreases muscle force, which correlates with decreased myosin regulatory light chain phosphorylation. Thus, we questioned whether the decline of estrogen in females that occurs with aging might alter the skeletal muscle phosphoproteome. C57BL/6J female mice (6 mo) were randomly assigned to a sham-operated (Sham) or ovariectomy (Ovx) group to investigate the effects of estrogen deficiency on skeletal muscle protein phosphorylation in a resting, noncontracting condition. After 16 wk of estrogen deficiency, the tibialis anterior muscle was dissected and prepped for label-free nano-liquid chromatography-tandem mass spectrometry phosphoproteomic analysis. We identified 4,780 phosphopeptides in tibialis anterior muscles of ovariectomized (Ovx) and Sham-operated (Sham) control mice. Further analysis revealed 647 differentially regulated phosphopeptides (Benjamini-Hochberg adjusted P value < 0.05 and 1.5-fold change ratio) that corresponded to 130 proteins with 22 proteins differentially phosphorylated (3 unique to Ovx, 2 unique to Sham, 6 upregulated, and 11 downregulated). Differentially phosphorylated proteins associated with the sarcomere, cytoplasm, and metabolic and calcium signaling pathways were identified. Our work provides the first global phosphoproteomic analysis in females and how estrogen deficiency impacts the skeletal muscle phosphoproteome.

Sex-specific Regulation of Prolactin Secretion by Pituitary Bradykinin Receptors.

Sex differences in the control of prolactin secretion are well documented. Sex-related differences in intrapituitary factors regulating lactotroph function have recently attracted attention. Sex differences in prolactinoma development are well documented in clinic, prolactinomas being more frequent in women but more aggressive in men, for poorly understood reasons. Kallikrein, the enzyme releasing kinins has been found in the pituitary, but there is no information on pituitary kinin receptors and their function. In the present work, we characterized pituitary bradykinin receptors (BRs) at the messenger RNA and protein levels in 2 mouse models of prolactinoma, Drd2 receptor gene inactivation and hCGβ gene overexpression, in both males and females, wild type or genomically altered. BR B2 (B2R) accounted for 97% or more of total pituitary BRs in both models, regardless of genotype, and was present in lactotrophs, somatotrophs, and gonadotrophs. Male pituitaries displayed higher level of B2R than females, regardless of genotype. Pituitary B2R gene expression was downregulated by estrogen in both males and females but only in females by dopamine. Activation of B1R or B2R by selective pharmacological agonists induced prolactin release in male pituitaries but inhibited prolactin secretion in female pituitaries. Increased B2R content was observed in pituitaries of mutated animals developing prolactinomas, compared to their respective wild-type controls. The present study documents a novel sex-related difference in the control of prolactin secretion and suggests that kinins are involved, through B2R activation, in lactotroph function and prolactinoma development.

ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma.

Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming.

Hypoxic Vasodilation is Augmented During the High versus Low Estrogen Phase of the Menstrual and Oral Hormonal Contraceptive Pill Cycle

BackgroundHypoxia elicits peripheral vasodilation to preserve oxygen delivery to metabolically active tissue. Hypoxic vasodilation, predominantly mediated by β‐adrenergic and nitric oxide mechanisms, is greater in adult female participants compared to adult male participants. Greater circulating estrogen in adult females has been purported to contribute to observed sex differences in hypoxic vasodilation. Nearly 80% of adult females in the United States will take oral hormonal contraceptive pills (OCPs) in their lifetime. Adult females taking OCPs exhibit greater β‐adrenergic receptor mediated vasodilation and nitric oxide production relative adult females with natural menstrual cycles (NC). Strategically utilizing the fluctuations of circulating estrogen that occur within a NC and OCP cycle, we aimed to examine the contribution of endogenous and exogenous estrogen on hypoxic vasodilation in female participants. We hypothesized female participants taking OCPs would exhibit greater hypoxic vasodilation relative to female participants with a NC. We further hypothesized hypoxic vasodilation would be greatest during the high estrogen (HE) phase of the menstrual or pill cycle compared to the low estrogen (LE) phase.MethodsTen female participants with a NC (25±1 yrs, 23±1 kg/m2) and ten female participants taking monophasic OCPs (24±1 yrs, 21±1 kg/m2) completed two study visits (IRB #2011312, NCT03606434). Participants were studied once during the LE phase of the menstrual or pill cycle (Cycle day: NC 3±1; OCP 5±1) and once during the HE phase of the menstrual or pill cycle (Cycle day: NC 15±1; OCP: 17±1). Forearm blood flow (venous occlusion plethysmography) and blood pressure (BP, finger plethysmography) were measured during normoxia and hypoxia (80% SpO2). Blood flow was normalized for BP and expressed as forearm vascular conductance (FVC).ResultsHypoxia elicited an increase in FVC (% change from baseline) that was greater during the HE phase (NC: 21±10%, OCP: 41±6%) of the menstrual/pill cycle compared to the LE phase (NC: 5±8%, OCP: 10±8%) in both NC and OCP participants (Main effect of phase, p&lt;0.01; Main effect of group, p=0.16; Interaction of phase and group, p=0.30).ConclusionHypoxic vasodilation is augmented in the HE phase of the menstrual and pill cycle in healthy young female participants, independent of whether the hormone is endogenous (NC) or exogenous (OCP). These data further our understanding of the role of estrogen in hypoxic vasodilation. These findings may have clinical implications for the vascular response to hypoxia in conditions of low estrogen (i.e., postmenopause) and/or estrogen excess, and warrant further investigation.

The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12–18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Examining Male Predominance of Severe COVID-19 Outcomes: A Systematic Review.

Although not universal, many epidemiological data sources signal that a higher proportion of males than females with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections have adverse outcomes, such as intensive care unit (ICU) admission and death. Though likely multifactorial, the various hypotheses that have been proposed as underlying factors behind this trend are related to greater smoking prevalence among males, testosterone (T) deficiency causing an inflammatory storm, androgen-driven pathogenesis of SARS-CoV-2, a protective effect of estrogen in females, and inborn errors of cytokine immunity. This review aims at examining the evidence and at assessing the likelihood that the factors being investigated are contributory to the reported trend of male predominance of severe COVID-19 cases. Sources were obtained using the PubMed database and were selected based on their relevance to one of the primary hypotheses attempting to explain the strong male sex bias of severe SARS-CoV-2 infections. Emphasis was placed on meta-analyses and population-based studies. Sources are current through February 22, 2022. A severe COVID-19 case or outcome is defined in this review as a progression of the SARS-CoV-2 virus that results in either admission to an ICU for management of symptoms and clinical stabilization or which leads to death. Although the trend of male predominance of severe COVID-19 cases is likely multifactorial, the hypothesis of T deficiency causing an inflammatory storm has support from many studies with limited conflicting evidence. An inborn error in cytokine immunity is also well supported, but it needs more studies to add support to the hypothesis. The immunologic protective effect of estrogen is supported by multiple studies, but it also has conflicting evidence. It appears less likely that the trend is caused solely by an increased prevalence of smoking among males or an androgen-driven pathogenesis, based on the extent of conflicting evidence.

Premenopausal and postmenopausal women during the COVID-19 pandemic.

The current global COVID-19 mortality rate is estimated to be around 3.4%; however, it is dependent on age, sex, and comorbidities.Epidemiological evidence shows gender disparities in COVID-19 severity and fatality, with non-menopausal females having milder severity and better outcomes than age-matched males. However, the difference vanishes when comparing postmenopausal women with age-matched men.It has been suggested that, to some extent, this is due to the protective role of female hormones, such as anti-Müllerian hormone and oestradiol (E2), in non-menopausal women.Oestrogens have been hypothesized to be crucial in modulating viral infection and the progression of the disease via an action on immune/inflammatory responses and angiotensin-converting enzyme type 2 expression. Hence, the most likely explanation is that, because the levels of oestrogen in females after menopause decrease, oestrogen no longer offers a beneficial effect as seen in younger females.The COVID-19 pandemic has highlighted the serious negative effects arising from the state of E2 deficiency. Therefore, hormone replacement therapy gains further support as the damaging effect of the decline in ovarian function affects many biological systems, and recently with the COVID-19 pandemic, oestrogen’s vital role within the immune system has become quite clear.However, additional clinical investigations regarding hormone replacement therapy are urgently needed to further verify the protective and therapeutic effects of E2 on menopausal women with COVID-19.

The Correlation between Pituitary Gonadotrophins, Gonadal Sex Steroid Hormone with Ferritin Level in Pubertal Females with Thalassemia Major at Wassit Province - Iraq 2020

Thalassemia Major still a growing disease in Iraq with no clear plan for prevention.&#x0D; Failure to get a secondary sexual character, amenorrhea, and then the inability to get pregnant is one the increasingly common problems in female patients with huge burden effects. Despite recent advances in iron chelation therapy, still, excess iron deposition in pituitary gonadotropic and gonadal cells remains one of the major causes for gonadal failure.&#x0D; Objectives: To evaluate the effect of iron overloads measured by serum ferritin on pituitary gonadotrophins measured by FSH, LH, and the gonadal sex steroid measured by estrogen in pubertal females with thalassemia Major.&#x0D; Methods: 41 female patients randomly selected in a cross-sectional study with diagnosed Thalassemia Major registered in Al-Kut Hereditary Blood Disease Center in the south of Iraq.&#x0D; Demographic data were evaluated including (age, type of chelation therapy, compliance for treatment and mean hemoglobin levels, and presence of amenorrhea). Serum ferritin, hemoglobin, FSH, LH, Estrogen levels were collected from patient's files. &#x0D; Results: the age of the studied sample were range from 14-43 years. The majority of the studied patients 33(80.5%) were suffering from primary amenorrhea and only six had a normal menstrual cycle. Twenty-six (63.4%) patients had serum ferritin levels of more than 3000 ng/dl.&#x0D; A low average serum FSH, LH, and Estrogen concentration were observed in the group with serum ferritin levels more than 3000ng/dl in a statistically significant p-value, 0.001, 0.002, and 0.003 respectively with inverse Pearson's correlation (-0.4 and p-value 0.0009 for FSH), (- 0.2 with no significant p-value 0.12, for LH) and (-0.3 with significant p. value 0.02 for estrogen level). &#x0D; Conclusions:&#x0D; In this study majority of females with thalassemia, Major suffer from disruption of pituitary gonadotropins and possible gonadal sex steroid. High ferritin still is a statistically significant risk factor for gonadal failure.&#x0D; The needs for more strict iron control, early screening, and proper treatment of gonadotropin and gonadal sex steroid deficiency around the age of 13 years are essential to be offered. More studies and a larger sample are needed to confirm and/or add other risk factors in pubertal thalassemic females.&#x0D; &#x0D; &#x0D;

A Case-Control Study of Paracoccidioidomycosis in Women: The Hormonal Protection Revisited.

Clinical observations have long suggested that women are protected against paracoccidioidomycosis. 17β-estradiol, the main female estrogen, inhibits conidia-to-yeast transformation (C-to-Y), which is required for the infection establishment. However, experiments in murine models have yielded conflicting results, suggesting that C-to-Y inhibition, alone, fails to explain the female-associated protection and that sexual hormones may also act by modulating the host’s immune responses. Therefore, this issue remains unsolved. Strikingly, no studies have compared the severity of paracoccidioidomycosis between men and women. This retrospective case-control study compared 36 women with 72 age-matched men for clinical–demographic, laboratory, and chest imaging findings. Overall, paracoccidioidomycosis in women presented the main features described in the acute/subacute and chronic forms seen in men. Women also showed similar demographic features and clinical–laboratory and imaging severity scores as men. We additionally reviewed 58 paracoccidioidin skin test surveys undertaken by volunteers from endemic areas. Data accumulated from 10.873 tests showed that females and males are infected with similar magnitudes (21.9% vs. 25.2%) and that reactivity steadily increased with age, peaking after the age of 60. We discuss the paradox of similar infection rates but much lower disease prevalence in women, considering the current pathogenetic views of paracoccidioidomycosis, and we raise alternative hypotheses to account for this paradox.

Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration

BackgroundThe male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation.MethodsThe morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant.ResultsThe results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage.ConclusionsThe prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

The Transcription Factor Ventral Anterior Homeobox 1 Modulates Circadian Time-Keeping and Fertility Through Direct Regulation of Vasoactive Intestinal Polypeptide Expression in the Suprachiasmatic Nucleus

Light provides the primary timing signal that enables fine-tuned behavioral and hormonal entrainment of circadian rhythms to the environment. Light is transmitted from the eye to the brain through the retinohypothalamic tract, where one target is the hypothalamic suprachiasmatic nucleus (SCN), which generates self-sustained circadian rhythms. The vasoactive intestinal polypeptide (VIP) expressing neurons of the SCN relay light information to peripheral cells and tissues through control of hormonal and nervous signals, allowing synchronization of molecular clocks located in individual cells throughout the body. Non-natural light cycles, ie shiftwork, and weakened SCN function through genetic manipulation, disrupt the body’s circadian rhythms, causing deregulated hormone release, metabolic disorders, and negative effects on reproductive systems such as irregular menstrual cycles and decreased sperm count. To further our understanding of how the SCN translates light information into neuroendocrine control of fertility, we conditionally deleted the SCN enriched transcription factor Ventral anterior homeobox 1 (Vax1) in post-developmental VIP neurons, generating Vax1-flox/flox:Vip-Cre+ (cKO) mice. To determine if the SCN timekeeping function was impacted in cKO mice, we single housed males and females with running wheels to examine activity during both 12-hour light/dark cycles and in constant darkness. Wheel-running behavior in constant darkness revealed a shortening of the endogenous free-running period (Tau) of the SCN. Aside from Tau, wheel running behaviors were comparable to controls. Weakened SCN output can negatively impact fertility. While on 12-hour light/dark cycles, we found a modest, but significant change in follicle stimulating hormone and estrogen in cKO females and a reduced sensitivity of GnRH neurons to kisspeptin in males. The changes in hormone release were associated with a slightly lengthened estrous cycle in cKO females and reduced sperm quality in cKO males. To identify the molecular origin of the shortened SCN period, we used immunohistochemistry and RNAscope to examine expression of Vip. We found that diestrus cKO females had a significant reduction in Vip expression at ZT16 and preliminary data suggest a reduction in the circadian clock gene Bmal1. Together, these studies identify a novel role of VAX1 in VIP neurons where VAX1 is required for VIP expression and circadian timekeeping. Loss of VAX1 in VIP neurons weakens SCN output, deregulating reproductive hormone release and modestly reducing reproductive function in both males and females.