Serum Gonadotropin Concentrations Research Articles

Effect of Ramadan Fasting on Sex Hormones in Infertile Male

Ramadan fasting is one of the 5 pillars of Islam and one of the most significant Ibadat (worships) of Islam. Throughout the world, millions of Muslims fast during Ramadan to fulfill this religious obligation. Aims: The aim of the study is to determine changes in the serum concentrations of gonadotropins, testosterone and prolactin hormones in infertile males after fasting of Ramadan and whether fasting improves fertility in the male. Participants and Methods: This is a case series study was conducted on 54 infertile male subjects aged (25-50 years) who fasted during Ramadan. Two blood samples were taken from each patient, one before and the other after fasting of Ramadan. Serum FSH, LH, prolactin and testosterone measurement was done by using Enzyme Linked Immune Sorbent Assay (ELISA). Results: There was no significant difference in serum FSH, LH, prolactin hormones when we compared them before and after Ramadan fasting. Concerning serum testosterone hormone, there was a decrease in its level after fasting but not reach significance when compared with its level before fasting. Conclusion: Serum levels of FSH, LH, prolactin and testosterone were unchanged after fasting of Ramadan.

Genotypic Sex and Severity of the Disease Determine the Time of Clinical Presentation in Steroid 17α-Hydroxylase/17,20-Lyase Deficiency

Context: Steroid 17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol, and excessive mineralocorticoid action. The clinical symptoms of hypocortisolemia are subtle. Aim: The clinical, biochemical, and molecular characteristics of patients with 17OHD were evaluated to determine the factors influencing the time of diagnosis and the management. Patients and Methods: Clinical data, steroid profiles by liquid chromatography-tandem mass spectrometry, and Sanger sequencing of the CYP17A1 gene was evaluated in 12 patients with 17OHD diagnosed between 2004 and 2020. Results: Median age of diagnosis was 13.9 (range: 0.04–29.5) years. Ten of 12 patients had 46,XY karyotype. Except for one boy with partial 17OHD, all patients had female external genitalia hence raised as females. The clinical presentation of 17OHD was earlier (median age: 7 years) in patients, who presented with severe hypertension, atypical genitalia, or positive family history (n = 6, 50%) than those without (median age: 15.3 years; p = 0.0005). The latter group presented with amenorrhea (n = 6, 50%). Steroid profile of patients uniformly showed a typical pattern of 17OHD regardless of the age at diagnosis. Serum gonadotropin concentrations were elevated in patients >12 years (n = 7), normal in pre-adolescents (n = 4), and low in a patient, who had a digenic inheritance of homozygous CYP17A1 and KISS1R mutations. Conclusions: Early clinical presentation and diagnosis in 17OHD are associated with symptomatic hypertension in both 46,XX and 46,XY patients or inadequate virilization of external genitalia in 46,XY partial 17OHD. In the absence of these, the clinical presentation is at late pubertal ages at which time amenorrhea and elevated gonadotropins are the hints for diagnosis.

Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice

Kisspeptin is a neuropeptide responsible for propagating the hypothalamic-pituitary-gonadal (HPG) axis and initiating puberty. Pubertal exposure to an immune challenge causes enduring sexual behavior dysfunction in males and females, but the mechanism underlying this stress-induced sexual dysfunction remains unknown. Previous findings show that stress exposure can downregulate the HPG axis in adult females. However, it is unclear whether stress induced HPG axis suppression is limited to adult females or also extends to males and to pubertal animal models. The current study was designed to investigate the sex-specific consequences of a pubertal immune challenge on specific components of the HPG axis. Six-week old pubertal male and female mice were treated with saline or with lipopolysaccharide, a bacterial endotoxin. Expression of hypothalamic Kiss1 and Kiss1R as well as serum concentrations of luteinizing hormone, follicle-stimulating hormone, and growth hormone were examined. Pubertal lipopolysaccharide treatment decreased hypothalamic Kiss1, but not Kiss1R, expression in both males and females. Furthermore, only males showed decreases in circulating luteinizing and follicle-stimulating hormones. These results show that pubertal immune challenge suppresses the HPG axis by inhibiting Kiss1 production and decreasing serum gonadotropin concentrations in pubertal males, but points to a different mechanism in pubertal females.

The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age.

Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated “free” serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20–22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at −80°C, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry. TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = −0.22) and sums of DEHP and DiNP metabolites (r = −0.24) and the sum of the metabolites of the high molecular weight phthalates (r = −0.21) were negatively correlated with TV (all p < 0.05). After adjustment for BMI adult serum total testosterone was positively associated with exposure to the following antenatal serum phthalate metabolites: mono-(2-ethylhexyl) phthalate (r = 0.26), MiNP (r = 0.18), the sum of metabolites for DEHP (r = 0.21) and DiNP (r = 0.18), and the sum of high molecular phthalates (r = 0.20) (p = 0.0005 to p = 0.02). Given sample size, storage duration and confounding through postnatal exposures, further studies are required.

Relationship between serum gonadotropin concentrations and thyroid volume in women with polycystic ovary syndrome.

Relationship between serum gonadotropin concentrations and thyroid volume in women with polycystic ovary syndrome.

Особливості аргіназного шляху метаболізму L-аргініну в сперматозоїдах чоловіків при різних формах патоспермії

The changes in arginase activity of spermatozoa and hormonal profile of peripheral blood of infertile men with various forms pathospermia have been studied. It has been found that arginase activity in the sperm cells of men with oligozoo-, antenozoo-, oligoastenozoo- and leucocytospermia is decreased in 2.1, 2.3, 2.4 and 3.3 times respectively. This indicates about inhibition of arginase pathway of L-arginine metabolism, which is not significantly dependent on the type of disruption of spermatogenesis. The most significant changes have been observed in infertile men with leucocytospermia since white blood cells stimulate the formation of reactive oxygen species, induction and development of oxidative and nitrative stress in spermatozoa. Inhibition of arginase pathway of L-arginine metabolism has adaptive role, which is to limit bioavailabil- ity of L-arginine and to prevent excessive formation of NO in cytotoxic concentrations to sperm cells. It has been noted changes in serum concentrations of gonadotropin and sex hormones in men with various forms of pathospermia. The most expressed significant changes were in levels of follicle stimulating hormone and testosterone. The concentration of follicle stimulating hormone in patients with oligozoospermia caused by hypogonadism is twice higher and in patients with leucocytospermia in 1.8 times higher than in fertile men. In patients with astenozoospermia this value is in 2.2 times lower than in normozoospermic samples but within the physiological norm. The testosterone level in men with oligozoospermia is in 1.6 times lower than in fertile men but within the physiological norm. It has been found that arginase inhibition of spermatozoa po6itively correlated with a decrease in their concentration in the ejaculate of infertile men with oligozoospermia (r =0.68).

Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women.

Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. In animal models, acute activation of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to induce gonadotropin release in the presence of sufficiently high estrogen levels. However, it is unknown whether the HPA axis has a similar influence on gonadotropin release in humans. This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study. The study sample comprised three distinct hormonal-based populations according to their levels of progesterone (PROG) and estradiol (E2): (i) low-PROG-low-E2, (ii) low-PROG-high-E2 and (iii) high-PROG-high-E2 women. A low dose (1 µg) of ACTH was administered to all study participants. Serum steroid and gonadotropin concentrations were measured prior to, and at 30 and 90 minutes after, intravenous ACTH administration. Mean serum cortisol levels increased significantly following ACTH administration in all groups (P<0.001). Similarly, the serum levels of 17-OH-PROG, androstenedione, dehydroepiandrosterone and testosterone increased significantly in all groups (P<0.01). The low-PROG-high-E2 and high-PROG-high-E2 groups exhibited a significant increase in LH and FSH levels (P<0.001), whereas the low-PROG-low-E2 group demonstrated blunted LH and FSH responses to ACTH administration (P<0.05). Testing was performed during the luteal phase of the natural menstrual cycle. Testing during the follicular phase might have elicited premature, or more pronounced, LH surges in response to ACTH administration. Our findings suggest a novel mechanism by which the adrenal cortex functions as a mediator of gonadotropin release. These findings contribute to a greater understanding of the influence of acute stress on reproductive endocrinology. Funding was received from the Erasmus University Medical Center. The authors have no conflicts of interest. EudraCT Number 2012-005640-14.

Quantitative analysis of total β-subunit of human chorionic gonadotropin concentration in urine by immunomagnetic reduction to assist in the diagnosis of ectopic pregnancy.

BackgroundThe initial diagnosis of ectopic pregnancy depends on physical examination, ultrasound, and serial measurements of total β-subunit of human chorionic gonadotropin (hCGβ) concentrations in serum. The aim of this study was to explore the possibility of using quantitative analysis of total hCGβ in urine rather than in serum by immunomagnetic reduction (IMR) assay as an alternative method to diagnose an ectopic pregnancy.MethodsWe established a standard calibration curve of IMR intensity against total hCGβ concentration based on standard hCGβ samples, and used an IMR assay to detect total hCGβ concentrations in the urine of pregnant women with lower abdominal pain and/or vaginal bleeding. The final diagnosis of ectopic pregnancy was based on ultrasound scans, operative findings, and pathology reports. In this prospective study, ten clinical samples were used to analyze the relationship of total hCGβ IMR signals between urine and serum. Furthermore, 20 clinical samples were used to analyze the relationship between urine IMR signals and serum levels of total hCGβ.ResultsThe calibration curve extended from 0.01 ng/mL to 10,000 ng/mL with an excellent correlation (R2=0.999). In addition, an excellent correlation of total hCGβ IMR signals between urine and serum was noted (R2=0.994). Furthermore, a high correlation between urine IMR signals and serum levels of total hCGβ was noted (R2=0.862).ConclusionAn IMR assay can quantitatively analyze total hCGβ concentrations in urine, and is a potential candidate for point-of-care testing to assist in the diagnosis of ectopic pregnancy.

Disturbances of sleep continuity in women during the menopausal transition.

The objective of the study was to evaluate the prevalence of sleep continuity disorders in women during menopausal transition, to evaluate the relationship between disturbances of sleep continuity and the severity of menopausal syndrome and the occurrence of various symptoms of this syndrome, as well as to evaluate the association between the presence of sleep disturbances and serum concentrations of gonadotropins, prolactin and sex hormones. Consecutive 140 women (mean age 54.4 ± 4.7 years) searching for the treatment in the Clinic for Gynaecological Endocrinology who reported symptoms of menopausal syndrome were investigated. The type and severity of disturbances of sleep continuity were evaluated using a survey based on the sleep related questions from Hamilton Depression Rating Scale. The severity of symptoms of menopausal syndrome was assessed using the Kupperman Index. The concentration of the following hormones in blood serum was tested: FSH, LH, 17β-estradiol, PRL, total testosterone, DHEAS and SHBG. Disturbances of sleep continuity were a prevalent complaint in the studied group of women. Difficulties in falling asleep were found in 57.8% of women, difficulties in maintaining sleep in 70%, waking up too early in 60.7%. The severity of all three types of sleep continuity disturbances was related to the severity of menopausal syndrome as measured with Kupperman Index (Spearman correlation coefficient r = 0.63, r = 0.61, r = 0.52, respectively; p < 0.001). Difficulties in maintaining sleep were negatively correlated with the concentration of FSH (r = - 0.19; p < 0.05), 17β-estradiol (r = - 0.19; p < 0.05) and SHBG (r = - 0.18; p < 0.05), difficulties in falling asleep negatively correlated with the concentration of 17β-estradiol in the blood serum (r = - 0.19; p < 0.05). Sleep continuity disturbances are frequently reported by women during the menopausal transition. Interventions aimed at reducing the symptoms of menopausal syndrome should be considered as important action to improve sleep quality in this population of patients.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome

Objective Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. Patients and methods 150 patients, aged C65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Results Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Conclusion Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged ≥65years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200ng/dl. Hypogonadism was found in 80 patients (53.3%). Serum gonadotropin concentrations were elevated in 43.7% of these patients, whereas 41.3% of hypogonadic patients showed normal and 15% low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Developmental androgen excess disrupts reproduction and energy homeostasis in adult male mice

Polycystic ovary syndrome is a common endocrine disorder in females of reproductive age and is believed to have a developmental origin in which gestational androgenization programs reproductive and metabolic abnormalities in offspring. During gestation, both male and female fetuses are exposed to potential androgen excess. In this study, we determined the consequences of developmental androgenization in male mice exposed to neonatal testosterone (NTM). Adult NTM displayed hypogonadotropic hypogonadism with decreased serum testosterone and gonadotropin concentrations. Hypothalamic KiSS1 neurons are believed to be critical to the onset of puberty and are the target of leptin. Adult NTM exhibited lower hypothalamic Kiss1 expression and a failure of leptin to upregulate Kiss1 expression. NTM displayed an early reduction in lean mass, decreased locomotor activity, and decreased energy expenditure. They displayed a delayed increase in subcutaneous white adipose tissue amounts. Thus, excessive neonatal androgenization disrupts reproduction and energy homeostasis and predisposes to hypogonadism and obesity in adult male mice.

Characteristics associated with suppression of spermatogenesis in a male hormonal contraceptive trial using testosterone and Nestorone®gels

Development of a male hormonal contraceptive has been challenging ascribable to the failure to adequately suppress spermatogenesis in 5-10% of men. Methods to identify incomplete suppressors early in treatment might identify men most responsive to male hormonal contraceptives. We hypothesized that serum hormone and gonadotropin concentrations after 4weeks of transdermal treatment with testosterone and Nestorone in a contraceptive trial would be associated with suppression of sperm concentrations to <1million/mL after 24weeks. Indeed, luteinizing hormone or follicle-stimulating hormone concentrations greater than 1IU/L after 4weeks of transdermal testosterone/nestorone treatment were 97% sensitive for predicting failure to suppress spermatogenesis after 24weeks of treatment. Serum nestorone concentrations were significantly associated with suppression, but serum testosterone concentrations were not. Early suppression of gonadotropins is associated with, but does not ensure, adequate suppression of spermatogenesis. This information may allow for rapid identification of non-responders in male hormonal contraceptive trials.

Serum AMH in Physiology and Pathology of Male Gonads

AMH is secreted by immature Sertoli cells (SC) and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process. AMH is also involved in testicular development and function. AMHs are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active SC proliferation. AMH rises rapidly in concentration in boys during the first month, reaching a peak level at about 6 months of age, and then slowly declines during childhood, falling to low levels in puberty. Basal and FSH-stimulated levels of AMH, might become a useful predictive marker of the spermatogenic response to gonadotropic treatment in young patients with hypogonadotropic hypogonadism. After puberty, AMH is released preferentially by the apical pole of the SC towards the lumen of the seminiferous tubules, resulting in higher concentrations in the seminal plasma than in the serum. Defects in AMH production and insensitivity to AMH due to receptor defects result in the persistent Müllerian duct syndrome. A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis. Lower serum AMH concentrations in otherwise healthy boys with cryptorchidism, who were compared with their age-matched counterparts with palpable testes, have been reported previously. AMH levels are higher in prepubertal patients with varicocele than in controls. This altered serum profile of AMH in boys with varicoceles may indicate an early abnormality in the regulation of the seminiferous epithelial function. Serum AMH is known to be valuable in assessing gonadal function. As compared to testing involving the administration of human chorionic gonadotropin, the measurement of AMH is more sensitive and equally specific. Measurement of AMH is very useful in young children, because serum gonadotropin concentrations in those who are agonadal are nondiagnostic in midchildhood and serum testosterone concentrations may fail to increase with provocative testing in children with abdominal testes.

Split daily recombinant human LH dose in hypogonadotrophic hypogonadism: a nonrandomized controlled pilot study

This prospective controlled nonrandomized pilot study was conducted to investigate whether split daily doses of recombinant human LH (rHLH) is more efficacious than the single daily dose in supporting follicular development and ovulation in primary hypogonadotrophic hypogonadism (HH). Twenty-seven women with HH received a 150 IU fixed daily subcutaneous dose of recombinant human FSH, supplemented by 75 IU daily dose of rHLH given either as a single dose (n=9; single-dose group) or four equally divided doses (n=18; split-dose group). Ovulation was defined by three efficacy end points: at least one follicle ⩾17mm in diameter, pre-ovulatory serum oestradiol ⩾400pmol/l and a midluteal progesterone ⩾25nmol/l. Although lacking statistical significance, the proportion of women in the rHLH split-dose group who fulfilled all three end points was higher than the single-dose group (72.2% versus 55.6%). Women in the split-dose group achieved higher serum oestradiol concentrations per follicle, endometrial thickness measurements and numbers of follicles than in the single-dose group (not statistically significant). The odds ratio for ovulation rate was 2.08 (not statistically significant). There were no serious untoward side effects. Administering rHLH in split daily doses could provide superior results compared with the traditional single daily dose.We conducted this clinical study to investigate whether a split daily dose protocol of recombinant human LH (rHLH) is more efficacious than the single daily dose in supporting follicular development and ovulation in primary hypogonadotrophic hypogonadism (HH). HH is an uncommon entity that can lead to very low or undetectable serum gonadotrophin concentrations. It manifests in anovulation, amenorrhoea and subsequent infertility. Twenty-seven women with HH received a 150 IU fixed daily subcutaneous dose of recombinant human FSH, supplemented by a 75 IU daily dose of rHLH given either as a single dose (n=9; single-dose group) or four equally divided doses (n=18; split-dose group). Ovulation was defined by these three efficacy end points: at least one follicle ⩾17mm in mean diameter, pre-ovulatory serum oestradiol concentration ⩾400pmol/l and a midluteal progesterone concentration ⩾25nmol/l. The proportion of women in the rHLH split-dose group who fulfilled all three end points was higher than the single-dose group (72.2% versus 55.6%). Women in the split-dose group achieved higher serum oestradiol concentrations per follicle, endometrial thickness measurements and numbers of follicles than in the single-dose group, without statistical significance. Women who received the split-dose regimen were more likely to have ovulation than the other group. We had no serious problematic side effects. Our results suggest that administering rHLH in split daily doses could provide superior results compared to the traditional single daily dose.

Skeletal status and body composition in young women with functional hypothalamic amenorrhea

Context: Functional hypothalamic amenorrhea (FHA) related to hypoestrogenism and hormonal status may influence skeletal homeostasis and body composition. The study aimed to evaluate hormones concentrations, body composition and bone strength in FHA cases. Patients and methods: Total body scans using DXA method (DPX-L, GE Lunar) were performed in a group of 27 women aged 21.8 years ± 3.9 with FHA related to weight loss. References of healthy control subjects were used to calculate Z-scores (age and gender matched), SD-scores (height and gender matched), and SDs-scores (weight and gender matched). Whole skeleton bone mineral content (TBBMC, g) and density (TBBMD, g/cm2), lumbar spine (L2–L4) bone mineral density (SBMD; g/cm2), lean body mass (LBM, g) and fat mass (FM, g) were investigated. Relative bone strength index was calculated as the TBBMC/LBM ratio. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, and prolactin (PRL) concentrations were assayed to characterize hormonal profile of FHA cases. Results: Hormonal evaluation in patients with FHA revealed significantly decreased serum concentrations of gonadotropins and estradiol. Serum LH concentrations were 1.47 ± 0.89 mIU/ml, FSH 4.44 ± 1.94 mIU/ml. Estradiol concentrations in serum were 27.08 ± 13.10 pg/ml. As evidenced by Z-scores, FHA cases had decreased SBMD, TBBMD and TBBMC Z-scores of −1.23 ± 0.90 (p < 0.0001), −0.72 ± 0.86 (p < 0.001), and −0.90 ± 1.40 (p < 0.01), respectively. Reduced FM, LBM and FM/LBM ratio Z-scores of −1.80 ± 2.28 (p < 0.001), −0.59 ± 1.49 (p < 0.05) and −0.74 ± 1.55 (p < 0.05), but not TBBMC/LBM Z-score of −0.54 ± 2.14 (ns) were noted in FHA cases compared with healthy control cases. TBBMC, TBBMD, TBBMC/LBM when BH- or BW-matched were normal as evidenced by SD-scores and SDs-scores. SBMD remained reduced when BH-matched (SD-score = –0.40 ± 0.86; p < 0.05) whereas FM and FM/LBM were lower than expected in healthy, both compared to BH- and BW-dependent references. The length of amenorrhea in months negatively correlated with SBMD Z-score (R = –0.39, p < 0.05), and SD-scores for SBMD (R = –0.48), TBBMD (R = –0.43), TBBMC (R = –0.46) (all p < 0.05) and positively with SDs-scores for FM (R = 0.44, p < 0.05). Conclusion: Patients with FHA were characterized by lower concentrations of serum FSH, LH and estradiol concentrations. Moreover, FHA cases had decreased FM and an imbalanced relationship between BW, FM, and LBM. Despite reduced BMD and BMC, bone strength was not significantly affected by FHA.

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

Nucleotide variations in mitochondrial DNA and supra-physiological ROS levels in cytogenetically normal cases of premature ovarian insufficiency

Premature ovarian insufficiency (POI) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotrophin concentration (FSH). It is a heterogeneous disorder with a multicausal pathogenesis; however, majority of cases are idiopathic. In idiopathic POI, involvement of unknown mechanisms may increase rate of oocyte apoptosis. Studies have shown that elevated reactive oxygen species (ROS) levels affect the quality of gametes. Mitochondrial mutations in different complexes of electron transport chain have been reported to disrupt the electron flow which lead to formation of more superoxide ions or increased levels of ROS. This study was aimed to screen the mitochondrial genome for variations in idiopathic POI (n = 25) and occult ovarian insufficiency (OI) (n = 5) patients. 30 patients diagnosed with POI and occult OI were enrolled in this study. Blood samples were collected from the patients and controls. DNA was extracted using phenol chloroform method. A total of 102 nucleotide variations were observed in patients as compared with 58 nucleotide variations in controls. 24% variations were found to be non-synonymous and 76% were synonymous. It was found that 48% variations were in complex I, 8% in complex III, 24% in complex IV, and 20% in complex V of electron transport chain. We found most of the non-synonymous mitochondrial variations in complex I (48%) of the respiratory chain which is the largest enzyme complex and is associated with oxidative stress. Some non-synonymous pathogenic alterations (p.M31T, p.W239C, p.L128Q) and non pathogenic alterations (ATPase6:p.T53I, ATPase6:p.L190F, ATPase6:p.L199L) were found to be significantly higher in cases as compared with controls. The preliminary data suggest that the mitochondrial mutations and subsequent decline in ATP levels may accelerate follicular atresia and lead to POI. The results of this preliminary study highlight the need to extend this study by analyzing large number of samples in different ethnic populations and analyze for ROS levels and mitochondrial mutations in oocytes as they are of different embryonic origin and develop in a different microenvironment.

Inherent capacity of the pituitary gland to produce gonadotropins is not influenced by the number of ovarian follicles ≥3 mm in diameter in cattle

We hypothesised that higher serum FSH concentrations in cattle with low v. high follicle numbers during follicular waves are caused by a different capacity of the pituitary gland to produce gonadotropins. Dairy cows with high (> or = 30; n = 5) and low (< or = 15; n = 5) follicle numbers were selected and serum concentrations of oestradiol and FSH during an oestrous cycle were measured. Cows were ovariectomised at oestrus and bled frequently up to 8 days after ovariectomy. After 33 days, cows were injected with gonadotropin-releasing hormone (GnRH) and bled intensively up to 8 h after GnRH injection. One day later, animals were injected with follicular fluid (FF) from bovine follicles and were bled intensively up to 2 days after the first injection. Serum concentrations of FSH and LH were measured. After 2 days, cows were killed and their pituitary glands collected. Prior to ovariectomy, serum oestradiol concentrations were similar between groups, whereas FSH concentrations were higher in cattle with low v. high numbers of follicles. No differences were detected in serum gonadotropin concentrations after ovariectomy, GnRH injection or FF challenge between groups. The results indicate that the inherent capacity of the pituitary gland to secrete gonadotropins does not differ between cattle with high v. low numbers of follicles during follicular waves.