Increase In Luteinizing Hormone Research Articles

P-588 Serum Luteinizing Hormone levels before progesterone supplementation are significantly associated with live birth rate in single euploid frozen embryo transfers performed in hormonal replacement cycles

Abstract Study question Do luteinizing hormone (LH) levels measured prior to initiating progesterone supplementation influence live birth rate (LBR) in artificial frozen-thawed single euploid blastocyst transfer cycles? Summary answer Serum LH levels, measured prior to progesterone initiation in artificial frozen-thawed single euploid blastocyst transfer cycles, are significantly associated with LBR. What is known already In the absence of a dominant follicle, estrogen supplementation in artificial endometrial preparation for frozen embryo transfer (FRET) can lead to a rise in endogenous LH levels, as observed in a natural cycle. Since the LH rise is a key feature in natural conception and the embryo, the endometrium, and the myometrium display receptors for LH, the rise observed during FRET preparation may have an impact on the clinical outcomes of the treatment. Previous studies found contradictory results hence none of them excluded embryo aneuploidy by implementation of preimplantation genetic testing for aneuploidies and the transfer of euploid embryos. Study design, size, duration Retrospective analysis of 639 frozen-thawed single euploid blastocyst transfer cycles performed in a tertiary referral IVF center from January 2018 to August 2023. Cycles with hormonal pre-treatment or pituitary suppression were excluded. Participants/materials, setting, methods Single euploid FRET cycles were included. Oral estradiol administration commenced on cycle-day 2/3. Estradiol, progesterone, and LH were measured at the start of endometrial preparation and up to 3 days before progesterone initiation, and the slope of LH was calculated. Patients were stratified in groups according to their LH values before progesterone administration, and the impact of LH on LBR and implantation rate was assessed. Logistic regression analysis was performed to adjust for potential confounders. Main results and the role of chance In total 639 cycles were included. Patients’ characteristics (mean+/-SD) were: age 33.2±5.9 years; BMI 27.5±4.9 kg/m2. The median duration of estrogen administration was 15 days (range: 11-27 days). The overall implantation rate and LBR were 65.9% (421/639) and 46.9% (300/639), respectively. Patients were stratified into six groups according to their LH levels prior to progesterone supplementation: <10th percentile (≤6mIU/ml, n = 57), p10th-p25th (>6 to ≤ 8.5mIU/ml, n = 81), p25th-p50th (>8.5 to ≤ 12.4mIU/ml, n = 176), p50th-p75th (>12.4 to ≤ 18.1mIU/ml, n = 180), p75th-p90th (>18.1 to ≤ 25.0mIU/ml, n = 91) and >p90th (>25.0mIU/ml, n = 54). A significant trend for higher LBR with increasing serum LH levels was observed (Cochran-Armitage Test, P = 0.041) but not for implantation rate (P = 0.158). Those with higher basal serum estradiol levels before estrogen supplementation had a steeper LH increase from basal to progesterone-supplementation day (0.40 mIU/mL higher per 10pmol/L increase in basal estradiol, P = 0.027). Regression analysis identified as independent predictors of LBR BMI (OR 0.96, 95%CI: 0.93-0.99) and embryo quality (CC vs. AA p < 0.001, CB vs. AA p = 0.027, BC vs. AA p = 0.013). Patients with steeper LH increases from estrogen to progesterone-supplementation day had higher LBR in both univariable (OR:1.27, 95%CI: 1.00–1.63, P = 0.052) and multivariable analyses (OR:1.26, 95%CI: 0.97–1.64, P = 0.085) but the difference didn’t reach statistical significance. Limitations, reasons for caution The retrospective design of the study is a limitation. Results should be interpreted with caution due to the small number of patients in the lowest and highest LH percentile groups. Wider implications of the findings The results of this study suggest that serum LH levels measured before progesterone supplementation may have an impact on the clinical outcome of artificial frozen-thawed blastocyst transfer cycles. Further studies with a higher sample size are necessary to confirm or refute our findings. Trial registration number not applicable

Effect of treatment of chronic hepatitis c virus patients with direct-acting anti-retroviral drugs on semen and hormonal parameters

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs.Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels.Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

IntroductionLong-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men. MethodsIn this proof-of-concept, single-site, open longitudinal pilot study, AAS dependent men with continuous AAS use and a desire to permanently discontinue use, were given endocrine therapy. The treatment included 25 mg clomiphene citrate (CC) every second day for 16 weeks, transdermal testosterone daily during the first four weeks, and if indicated, human chorionic gonadotropin (hCG) injections for a maximum of eight weeks. Physical exams including blood collection and online questionnaires were completed every four and two weeks, respectively. ResultsTen participants, with median age 32 years (interquartile range 30–45), with mean ± standard deviation AAS use of 11 ± 4 years, completed the CC intervention. Seven participants received hCG as part of their treatment protocol. Mild adverse events included headaches, dizziness, and mood swings, and no serious adverse events occurred. During the intervention, there was a decrease in levels of hematocrit, hemoglobin and ALT (alanine aminotransferase), as well as an increase in serum FSH (follicle stimulating hormone), LH (luteinizing hormone) and SHBG (sex hormone binding globulin). Five of ten participants reached a total testosterone level within normal range (9–30 nmol/l). The HPG axis response varied greatly among participants, and was not aligned with the severity of ASIH related withdrawal symptoms. ConclusionsThe findings from this proof-of-concept study may guide future randomized controlled trials aiming to investigate potential endocrine therapeutic approaches to ASIH.

The influence of body composition on the response to dynamic stimulation of the endocrine pituitary-testis axis.

Testosterone treatment is generally not recommended in men with obesity induced low serum testosterone. However, distinguishing this condition from overt testosterone deficiency in men with obesity where treatment should be initiated is a diagnostic challenge and tools to differentiate these conditions are scarce but could be of important clinical relevance. To investigate the association between body composition and dynamic responses of the pituitary-testis axis in men. Single-center cross-sectional study including 112 healthy men. Participants went through a full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of luteinizing hormone (LH) secretion (gonadotropin-releasing hormone (GnRH)-test) and testosterone secretion (choriogonadotropin (hCG)-test). A subset (N = 78) further had a DXA-scan performed. A higher body mass index (BMI) was associated with lower basal serum LH (BU = -0.44, 95% CI: -0.88--0.01, p = 0.04). The GnRH-stimulated LH increase was not significantly associated with BMI (BU = -0.10, 95% CI: -0.72-0.51, p = 0.74). Furthermore, a high BMI was associated with low basal testosterone (BU -0.02, 95% CI: -0.03--0.02, p < 0.001), and free testosterone (BU -15.0, 95% CI: -19.9--10.0, p < 0.001) and men with overweight and obesity had significantly lower testosterone (9%, p = 0.003 and 24%, p < 0.001) and free testosterone (25%, p = 0.006 and 50%, p < 0.001) concentrations compared to men with normal weight. The HCG-stimulated testosterone increase was significantly less dependent on BMI compared to the influence of BMI on basal testosterone concentrations (p = 0.04 for the interaction). Dynamic sex hormone responses following pituitary-testis axis stimulation were less dependent on BMI, compared to the influence of BMI on basal hormone concentrations and could potentially assist clinical decision making in patients with obesity suspected of testosterone deficiency.

Androgen State and Erectile Function in Men with Chronic Distress

The objective: to study the state of androgen supply and erectile function in men with chronic distress. Materials and methods. We examined 30 internally replaced males (Average age, M±σ=50.50±3.83) with manifestations of chronic distress (Group I) and 20 practically healthy males (Group II), (Average age, M±σ=51.95±4.60). All men underwent general clinical examination, body mass index evaluation, assessment of depression according to Hospital Anxiety and Depression Scale (HADS), assessment of symptoms of androgen deficiency according to the Aging Males’ Symptoms (AMS). Severity of erectile dysfunction was evaluated according to the International Index of Erectile Function scale (IIEF). The following parameters were determined in blood serum: luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free testosterone (TF), estradiol (E), cortisol (K). Results. According to the HADS scores in group I men, the average anxiety domain score was 12.03±1.50 points, the average depression domain score was 13.93±1.49, and the total score was 26.0±2.64 points. In patients of group II, the average anxiety domain score was 2.20±0.88 points, the average depression domain score was 2.60±1.00, and the overall score was 4.80±1.40 points. The comparison of the total score of group I and the total score of group II is statistically significant (p&lt;0.05). According to the AMS, in men of group I, androgen deficiency was more expressed comparing to the control group (45.93±3.30 and 13.30±2.04 points, respectively, p&lt;0.001). Analysis of the IIEF-15 questionnaire revealed a decrease in all indicators of erectile function in men of group I comparing to group II. A study of the hormonal state showed a decrease in the level of TT in men of group I compared to the indicators of group II: 9.30±2.84 and 15.27±0.96 ng/ml, respectively (p&lt;0.001). The average TF levels in group I were reduced comparing to group II and reached 10.23±1.38 and 17.39±1.03 pg/ml, respectively (p&lt;0.001). The levels of LH and FSH in men of group I were within normal age-related fluctuations and did not differ statistically significantly from similar levels of group II. The average E level in men with chronic distress was significantly increased comparing to the control group and reached up to 0.25±0.05 versus 0.11±0.03 nmol/l, respectively (p&lt;0.001). The average C level in men with chronic distress was significantly increased comparing the control group and reached up to 13.33±2.19 versus 6.72±1.33 μg/dL, respectively (p&lt;0.001). Conclusions. 1. The survey results indicate that chronic distress is a factor that worsens sexual function in men. In addition to erectile dysfunction, as evidenced by a decrease in the corresponding IIEF integrative indicator 15 «erectile function», the survey found a decrease in both the frequency of occurrence and the degree of sexual desire, a deterioration in orgasmic sensations in the form of a decrease in the frequency of ejaculation and orgasms. 2. Cortisol is an important hormone that forms protective reaction in stressful situations, but loses its positive properties during chronic distress. A prolonged increase in cortisol levels can lead to a pathological condition accompanied by an increase in BMI, depression, anxiety, decreased testosterone levels and ED. 3. A decrease in testosterone levels in chronic distress and visceral obesity in men is not accompanied by a compensatory increase in LH and FSH levels. This can be explained by increased aromatization of testosterone in visceral adipose tissue and a decrease in the pituitary gland’s response to the development of androgen deficiency as a result of combined damage to the central and peripheral parts of the regulation of testosterone synthesis.

Elagolix Represents a Less Invasive and Cheaper Option than Injectable GnRH Antagonist for Ovulation Suppression in IVF.

The injectable GnRH antagonists have traditionally been used for ovulation suppression during controlled ovarian hyperstimulation in IVF, leading to increased painful daily injections and cost. The use of the oral GnRH antagonist elagolix for ovulation suppression in IVF has not been studied. A retrospective cohort study of patients undergoing IVF received either oral elagolix 50 mg every other day or ganirelix/cetrotide injection daily for ovulation suppression during controlled ovarian hyperstimulation. A total of 269 patients, 173 in the elagolix group and 96 in the ganirelix/cetrotide group, were included. The main outcome was the suppression of luteinizing hormone (LH) blood levels reflecting ovulation suppression. The age, body mass index, AMH levels, baseline FSH, antral follicles count, the dose of medications used, the number of days of ovarian stimulation, and peak estradiol (E2) levels were similar in both groups. When blood LH and E2 levels were measured before the intake and the day after intake of either elagolix or ganirelix/cetrotide, both groups had significant and similar drop in LH levels and increase in E2 levels. When comparing the IVF cycle outcomes in both groups, the number of oocytes retrieved, the number of mature oocytes, the fertilization rate, the blastocyst formation rate, the euploidy rate and the endometrial lining thickness at the time of the trigger were all similar. Oral GnRH antagonist, a much cheaper and less invasive medication that is used at a lower frequency, showed comparable ovulation suppression to the costly injectable GnRH antagonist. Further studies are required to evaluate the effect of oral GnRH antagonist on endometrial lining receptivity and pregnancy outcomes especially when using fresh embryo transfer IVF protocols.

Pubertal Development in Girls with Beta Thalassaemia and Assessment of the Adequacy of Chelation Therapy: A Quasi-experimental Study

Introduction: Beta thalassaemia is the most prevalent hereditary autosomal disorder, significantly impacting endocrine function during pubertal development. The pathology is rooted in the excessive deposition of iron in vital organs. If left untreated, this condition leads to serious morbidity and mortality. Hypogonadism stands as the most common endocrine complication. Aim: To observe pubertal development in girls with thalassaemia and evaluate the adequacy of chelation therapy in such patients by measuring levels of Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), oestrogen, and serum ferritin. Materials and Methods: A quasi-experimental study was conducted at the Thalassaemia Clinic at the Department of Obstetrics and Gynaecology, Burdwan Medical College, Purba Bardhaman, West Bengal, India involving 300 diagnosed Beta Thalassaemia Major (BTM) (case) patients aged 13 to 17 years over a period of one and a half years (January 2020 to June 2021). The girls in the study groups were sequentially enrolled from the Outpatient Department of the Thalassaemia Clinic after meeting inclusion and exclusion criteria. Demographic data, anthropometric measurements, and Sexual Maturity Rating (SMR) were recorded. Hormonal assays of serum FSH, LH, oestrogen, and serum ferritin levels were conducted. Thalassaemic girls with serum ferritin levels exceeding 500 ng/mL received chelation therapy. Serum ferritin levels were measured at two-month intervals for up to six months, with reassessment of serum FSH, LH, oestrogen, and ferritin levels at the end of the six-month period. Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) version 27.0, Microsoft excel spreadsheet, and Epi Info 7. Results: A total of 190 (63.3%) of the thalassaemic girls were aged 13 to 15 years, with a mean Body Mass Index (BMI) of 22.5000±2.6100 kg/m2 , and 74 of them (38.94%) experienced menarche in this age group. Out of 300 cases, 269 thalassaemic girls (89.6%) received chelation therapy, and 89 cases (33.09%) reached menarche after chelation therapy. A significant (p&lt;0.0001) increase in mean LH and FSH levels was observed after chelation therapy. The mean ferritin level decreased from 3168.85 ng/mL to 2227.24 ng/mL following chelation therapy. Conclusion: Pubertal development failure is common in beta thalassaemic girls. Intervention in the form of adequate chelation therapy in girls with high serum ferritin levels yielded favourable outcomes, as evident from serum gonadotropin and oestrogen levels.

Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population.

To determine the association of serum kisspeptin, leptin, and other hormonal profile with non-obstructive azoospermia (NOA) in infertile male subjects. This cross-sectional study was conducted at Australian Concept Infertility Medical Center, and Ziauddin University, Karachi from March 2018 to March 2020. The duration of the study was two years. Serum samples of 106 azoospermic participants were taken. Division of the subjects was done on a histological basis into obstructive azoospermia (OA) n=36, NOA n=70 which were further divided into spermatid maturation arrest (SMA), n=41, and sertoli cell-only syndrome (SCOS) n=29. Serum kisspeptin and leptin were measured by ELISA (Cloud-Clone Corp). The follicle-stimulating hormone (FSH) (p<0.01), luteinizing hormone (LH) (p<0.01), thyroid-stimulating hormone (TSH) (p<0.01), and estradiol (p<0.01) was significantly high in the NOA group. However, kisspeptin was significantly decreased (p<0.01) in the NOA group. In the multivariate analysis after adjusting for other variables, the results showed that with the decrease in kisspeptin, the chances of being NOA were increased. Moreover, with the increase in Leptin, FSH, LH, and TSH the chances of being NOA were significantly enhanced. Serum kisspeptin, leptin, FSH, LH, TSH, and estradiol can be a potential marker for NOA in terms of better diagnosis, targeted therapeutic management, and the decision to proceed with surgical intervention.

25 Role of Kndy and Arcuate Kiss1r-Containing Neurons in the Preovulatory Luteinizing Hormone Surge and Puberty Onset of Female sheep

Abstract Neurons within the arcuate nucleus (ARC) of the hypothalamus containing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) have an important role in regulating the pulsatile secretion of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH). In sheep, kisspeptin neurons also contribute to the LH surge, as kisspeptin receptor (Kiss1r) antagonist administration reduces surge amplitude by 50% and KNDy neurons are likely involved, based on increased Fos expression at the time of the surge. However, the extent to which kisspeptin acts within the ARC regulate the GnRH/LH surge remains unclear. Thus, herein we tested the hypothesis that deletion of KNDy or ARC Kiss1r-containing neurons would impair the LH surge. Adult female sheep received bilateral injections targeting the ARC of NKB-saporin (NKB-SAP, n = 8), kisspeptin-saporin (Kiss-SAP, n = 10), or blank-saporin (Blank-SAP, n = 7) as a control. In other work, NKB-SAP lesioned over 90% of ovine KNDy neurons, while Kiss-SAP lesioned 67% of Kiss1r-containing cells without affecting KNDy or GnRH cell number. Ewes were also ovariectomized and a subcutaneous silastic estradiol (E2) implant was inserted at the time of neurosurgery. Two artificial luteal phases were simulated with progesterone-containing CIDRs, immediately followed by E2 treatment via implants to induce an LH surge. Blood samples were collected every two to four hours over two days and analyzed for LH via radioimmunoassay. LH surge amplitude in six of eight NKB-SAP ewes (49.5 ± 11.7 ng/mL) was significantly reduced compared with Blank-SAP control ewes (156.7 ± 20.2 ng/mL, p = 0.0001), a reduction similar to that produced by treatment with a Kiss1r antagonist. Nine of ten Kiss-SAP treated ewes displayed little to no increase of LH at the time of the expected surge (16.6 ± 5.3 ng/mL, p &amp;lt; 0.0001). Lesion effectiveness is currently being assessed by RNAscope, however all Kiss-SAP animals examined to date have significantly reduced ARC Kiss1r cell numbers except a single ewe which exhibited a normal LH surge. Based on these data, we propose that in ewes, KNDy neurons contribute to, but are not required for, the LH surge. In contrast, ARC Kiss1r-containing cells are essential for a functional LH surge. Given these results, we are currently assessing the role of ARC Kiss1r neurons in ovine puberty using a similar approach. Our data to date shows that time to puberty onset is similar for Kiss-SAP, Blank-SAP, and non-surgical control animals as measured by an increase in progesterone (p = 0.35). Blood samples to detect LH pulses and the LH surge are currently being analyzed, as are ARC Kiss1r cell numbers.

OR25-04 Factors Affecting Testosterone Concentrations In Men: Individual Participant Data Meta-analyses From The Androgens In Men Study

Abstract Disclosure: R.J. Marriott: None. K. Murray: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. B.B. Yeap: None. Different factors modulate circulating testosterone in men, impacting interpretation of reference ranges. We aimed to clarify factors associated with variations in sex hormone concentrations by conducting individual participant data (IPD) meta-analyses of prospective cohort studies of adult men with total testosterone measured using mass spectrometry. The Androgens In Men Study protocol was submitted to PROSPERO (23 July 2019), registered (20 November 2019; CRD42019139668) and published (BMJ Open 2020; 10: e034777). A systematic review (14 June-31 December 2019) identified prospective cohort studies (BMJ Open 2021; 11: e048013). IPD data were requested. Cross-sectional analyses related total testosterone (measured using mass spectrometry), sex hormone binding globulin (SHBG), luteinising hormone (LH), dihydrotestosterone (DHT) and estradiol (also measured using mass spectrometry) concentrations to sociodemographic, lifestyle, and health factors. Summary curves and effect estimates with 95% confidence intervals (CIs) were obtained using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (25,149 men). There was a non-linear association of testosterone with age, with negligible change among men aged 17-70 years (1SD increase about age 43.5, from 35.7 to 51.3 years -0.27 nmol/L, CI -0.71 to 0.18) and decreasing testosterone with age for men &amp;gt;70 years (1SD increase about age 84.5, from 76.7 to 92.3 years -1.55 nmol/L, CI -2.05 to -1.06). Testosterone was inversely associated with BMI (1SD increase about 27.5 kg/m2, from 25.5 to 29.6 kg/m2 -2.42 nmol/L, CI -2.70 to -2.13). Testosterone concentrations were lower for men who: were married/de facto (-0.57 nmol/L); undertook ≤75 minutes vigorous physical activity/week (-0.51 nmol/L); former smokers (-0.34 nmol/L); had hypertension (-0.53 nmol/L), cardiovascular disease (-0.35 nmol/L), cancer (-1.39 nmol/L), or diabetes (-1.43 nmol/L); all CIs excluded zero. SHBG increased with age (per SD increase in age 11.3 nmol/L, CI 9.0 to 13.6) and decreased with BMI (per SD increase in BMI -5.9 nmol/L, CI -6.9 to -5.0). There was little change in mean LH with age in men &amp;lt;70 years (1SD increase in age 0.10 IU/L, CI -0.08 to 0.28), but an increase in LH with age in men ≥70 years (1SD increase in age 4.14 IU/L, CI 3.71 to 4.56). DHT and estradiol were less prominently associated with these factors. Multiple factors are associated with variation in male testosterone and SHBG concentrations, with evidence of primary impairment of testicular hormone production after age 70 years. Interpretation of testosterone results in individuals needs to account for these factors, especially age &amp;gt;70 years, BMI, diabetes and cancer. Further research is needed to determine health impacts of declining testosterone in older men. Presentation Date: Saturday, June 17, 2023

SAT606 Comparison Of Psychosocial And Immune/Inflammatory Stress On Luteinizing Hormone Pulsatile Secretion

Abstract Disclosure: J. Jang: None. M.J. Kreisman: None. K.M. Breen Church: None. Stress induces a physiological response in the body to return to the homeostatic state. It is recognized that many stress types impair reproduction, but the mechanisms conveying inhibition may be distinct and stressor-dependent. Our research aims to understand how stress inhibits the neuroendocrine mechanisms controlling the pulsatile release of luteinizing hormone (LH). This is especially important because pulsatile LH is pivotal to reproductive health in males and females. Immune/inflammatory stressors such as lipopolysaccharides (LPS) cause an inflammatory response, producing peripheral cytokines that can signal to the brain in distinct ways compared to the neural mechanisms employed in response to psychosocial stress. However, how LPS disrupts the neural mechanisms involved in gonadotropin pulsatility is still unknown. Here, we compared the alteration in LH pulses in response to psychosocial restraint stress or immune/inflammatory LPS stress and sought to understand stress-specific regulation of the upstream targets controlling LH synthesis and secretion. Our initial observations demonstrated, in ovariectomized (OVX) female mice, that restraint stress elicited suppression rapidly, within 30 minutes; yet, the response to LPS was delayed, occurring approximately 90 minutes from injection. Therefore, we investigated the prolonged response of the stressors on LH pulses, observing LH pulse profiles 90 minutes to 180 minutes after the initiation of stress. Restraint stress significantly suppressed mean LH, resulting from a suppression of pulse frequency. LPS injected intraperitoneal (IP, 1.5 ug/g) also significantly suppressed mean LH. In contrast to restraint stress, LPS induced a reduction in both frequency as well as LH pulse amplitude. We conducted two follow-up experiments to investigate the lowered LH pulse amplitude during immune/inflammatory stress. The first study assessed hypothalamic kisspeptin gene expression and pituitary LHβ and GnRH receptor expression, in LPS versus restraint animals, to test whether altered gene transcription in LPS animals resulted in lowered LH secretion. The results of this experiment are still pending. The second study tested the LH response to a single bolus of GnRH or kisspeptin. Interestingly, we found equivalent LH increases, to either agonist, in saline versus LPS-treated animals. Collectively, these data indicate that both restraint and immune/inflammatory stress inhibit LH pulse frequency. However, the endogenous LH pulse profiles suggest an additional stressor-specific mechanism that lowers pulsatile LH during immune/inflammatory stress via LPS. Identification of stress pathways that alter endocrine hormones is critical as it allows for the development of therapeutics and medications to treat endocrine disorders. Presentation: Saturday, June 17, 2023

Synergistic Action of Virgin Coconut Oil and Clomiphene in Reversing Endocrine Dysregulation in Letrozole-Model of Polycystic Ovarian Syndrome in Rats: Role of Nrf2/HMOX-1 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder in women's reproductive age. Currently, the pathophysiology of PCOS is unclear, and the limited treatment options are unsatisfactory. Virgin coconut oil (VCO) is functional food oil associated with pharmacological effects in reproductive disorders. Therefore, we aimed to evaluate whether VCO could enhance clomiphene (CLO) therapy against PCOS in female rats. Rats were randomly divided: (1) Control, (2) PCOS model, (3) PCOS + CLO, (4) PCOS + VCO, and (5) PCOS + CLO + VCO. The PCOS was induced via daily letrozole (1 mg/kg, orally) administration for 21 days. After the PCOS induction, CLO, VCO, and CLO + VCO were administered from days 22 to 36. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estrogen, progesterone, and prolactin were estimated. Polymerase chain reaction gene expression for nuclear factor-erythroid-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), catalase (CAT), glutathione reductase (GSR), LH receptor (LHr), androgen receptor (AR), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and caspase-3 were analyzed. The letrozole-induced PCOS caused considerable increases in GnRH, LH, prolactin, estrogen, and testosterone, whereas FSH decreased significantly compared to the control. The gene expression of Nrf2, HO-1, CAT, and GSR were markedly diminished, while IL-1β, TNF-α, caspase-3, AR, and LHr prominently increased compared to control. Interestingly, the CLO and VCO separately exerted anti-inflammatory and endocrine balance effects. However, VCO-enhanced CLO effect in LH, prolactin and testosterone, Nrf2, HO-1, CAT, GSR, and AR. VCO may synergize with CLO to depress hyperandrogenism and oxidative inflammation in PCOS.

Protective Role of Rosa damascena Miller hydroalcoholic extract on Oxidative Stress Parameters and Testis Tissue in Rats Treated with Sodium Arsenite

Regarding the strong antioxidant properties of Rosa damascene extract, this study aimed to investigate the protective role of Rosa damascene Miller hydroalcoholic petal extract on oxidative stress parameters and testis tissue in rats treated with sodium arsenite. To this end, 30 male rats were divided into five groups, including control, positive control (treated with arsenite), and three groups of patients affected by sodium arsenite with 150 mg/kg, 300 mg/kg, and 450 mg/kg Rosa damascene extract for 34 days by gavage. The animals were then anesthetized, and the blood samples were collected from the heart. The left testis was removed for histopathological studies. The findings revealed that Sodium arsenite in the positive group caused a significant reduction in TAC, testosterone, and serum Luteinizing hormone (LH) and a significant increase in serum Malondialdehyde. In addition, there was no statistically significant difference among the groups regarding the amount of Follicle-stimulating hormone (FSH). Moreover, the consumption of Rosa damascene extract with sodium arsenite caused a significant increase in testosterone, LH, and FSH compared to the positive control group. Histopathological results showed that in the experimental group receiving a dosage of 300 mg/kg b.w and the control group, the number of sperm tubes increased, and the germinal epithelium’s thickness was appropriate. Daily treatment with Rosa damascene extract with a dosage of 300 mg/kg b.w for 34 days could improve the changes caused by sodium arsenite and reduce Malondialdehyde levels. Thus, it seems that Rosa damascene hydroalcoholic extract can effectively improve the male reproductive system’s function.

Interindividual variation of progesterone elevation post LH rise: implications for natural cycle frozen embryo transfers in the individualized medicine era

BackgroundThe key to optimal timing of frozen embryo transfer (FET ) is to synchronize the embryo with the receptive phase of the endometrium. Secretory transformation of the endometrium is induced by progesterone. In contrast, detection of the luteinizing hormone (LH) surge is the most common surrogate used to determine the start of secretory transformation and to schedule FET in a natural cycle. The accuracy of LH monitoring to schedule FET in a natural cycle relies heavily on the assumption that the period between the LH surge and ovulation is acceptably constant. This study will determine the period between LH rise and progesterone rise in ovulatory natural menstrual cycles.MethodsRetrospective observational study including 102 women who underwent ultrasound and endocrine monitoring for a frozen embryo transfer in a natural cycle. All women had serum LH, estradiol and progesterone levels measured on three consecutive days until (including) the day of ovulation defined with serum progesterone level exceeding 1ng/ml.ResultsTwenty-one (20.6%) women had the LH rise 2 days prior to progesterone rise, 71 (69.6%) had on the day immediately preceding progesterone rise and 10 (9.8%) on the same day of progesterone rise. Women who had LH rise 2 days prior to progesterone rise had significantly higher body mass index and significantly lower serum AMH levels than women who had LH rise on the same day with progesterone rise.ConclusionThis study provides an unbiased account of the temporal relationship between LH and progesterone increase in a natural menstrual cycle. Variation in the period between LH rise and progesterone rise in ovulatory cycles likely has implications for the choice of marker for the start of secretory transformation in frozen embryo transfer cycles. The study participants are representative of the relevant population of women undergoing frozen embryo transfer in a natural cycle.

Hindbrain Adenosine 5-Triphosphate (ATP)-Purinergic Signaling Triggers LH Surge and Ovulation via Activation of AVPV Kisspeptin Neurons in Rats.

Ovulation disorders are a serious problem for humans and livestock. In female rodents, kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) are responsible for generating a luteinizing hormone (LH) surge and consequent ovulation. Here, we report that adenosine 5-triphosphate (ATP), a purinergic receptor ligand, is a possible neurotransmitter that stimulates AVPV kisspeptin neurons to induce an LH surge and consequent ovulation in rodents. Administration of an ATP receptor antagonist (PPADS) into the AVPV blocked the LH surge in ovariectomized (OVX) rats treated with a proestrous level of estrogen (OVX + high E2) and significantly reduced the ovulation rate in proestrous ovary-intact rats. AVPV ATP administration induced a surge-like LH increase in OVX + high E2 rats in the morning. Importantly, AVPV ATP administration could not induce the LH increase in Kiss1 KO rats. Furthermore, ATP significantly increased intracellular Ca2+ levels in immortalized kisspeptin neuronal cell line, and coadministration of PPADS blocked the ATP-induced Ca2+ increase. Histologic analysis revealed that the proestrous level of estrogen significantly increased the number of P2X2 receptor (an ATP receptor)-immunopositive AVPV kisspeptin neurons visualized by tdTomato in Kiss1-tdTomato rats. The proestrous level of estrogen significantly increased varicosity-like vesicular nucleotide transporter (a purinergic marker)-immunopositive fibers projecting to the vicinity of AVPV kisspeptin neurons. Furthermore, we found that some hindbrain vesicular nucleotide transporter-positive neurons projected to the AVPV and expressed estrogen receptor α, and the neurons were activated by the high E2 treatment. These results suggest that hindbrain ATP-purinergic signaling triggers ovulation via activation of AVPV kisspeptin neurons.SIGNIFICANCE STATEMENT Ovulation disorders, which cause infertility and low pregnancy rates, are a serious problem for humans and livestock. The present study provides evidence that adenosine 5-triphosphate, acting as a neurotransmitter in the brain, stimulates kisspeptin neurons in the anteroventral periventricular nucleus, known as the gonadotropin-releasing hormone surge generator, via purinergic receptors to induce the gonadotropin-releasing hormone/luteinizing hormone surge and ovulation in rats. In addition, histologic analyses indicate that adenosine 5-triphosphate is likely to be originated from the purinergic neurons in the A1 and A2 of the hindbrain. These findings may contribute to new therapeutic controls for hypothalamic ovulation disorders in humans and livestock.

Socially Induced Infertility in Naked and Damaraland Mole-Rats: A Tale of Two Mechanisms of Social Suppression.

The naked mole-rat (Heterocephalus glaber) and the Damaraland mole-rat (Fukomys damarensis) possess extreme reproductive skew with a single reproductive female responsible for reproduction. In this review, we synthesize advances made into African mole-rat reproductive patterns and physiology within the context of the social control of reproduction. Non-reproductive female colony members have low concentrations of luteinising hormone (LH) and a reduced response of the pituitary to a challenge with gonadotropin releasing hormone (GnRH). If the reproductive female is removed from the colony, an increase in the basal plasma LH and increased pituitary response to a GnRH challenge arises in the non-reproductive females, suggesting the reproductive female controls reproduction. Non-reproductive male Damaraland mole-rats have basal LH concentrations and elevated LH concentrations in response to a GnRH challenge comparable to the breeding male, but in non-breeding male naked mole-rats, the basal LH concentrations are low and there is a muted response to a GnRH challenge. This renders these two species ideal models to investigate physiological, behavioural and neuroendocrine mechanisms regulating the hypothalamic-pituitary-gonadal axis. The recently discovered neuropeptides kisspeptin and RFamide-related peptide-3 are likely candidates to play an important role in the regulation of reproductive functions in the two mole-rat species.

Associations between COVID-19 infection and sex steroid hormones.

AimsCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and within a few months of the first outbreak, it was declared a global pandemic by the WHO. The lethal virus SARS-CoV-2 is transmitted through respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors are highly expressed in many tissues, including testes. Therefore, the objective of this study was to summarize the available literature regarding the correlation between sex hormone levels and COVID-19.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were reviewed systematically through August 2022 for studies comparing sex hormone levels between different patient groups: COVID-19 versus no COVID-19, more severe versus less severe COVID-19, and non-survivors versus survivors. Various types of clinical research reporting sex hormone levels, including free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-oestradiol (E2), the oestradiol-to-testosterone ratio (E2/T), prolactin (PRL), and sex hormone-binding globulin (SHBG), were included. Random- or fixed-effects models were used to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity among the studies was assessed by the I2 index, and data analyses were performed using meta-analysis with Stata version 12.0.ResultsTwenty-two articles that included 3369 patients were ultimately included in the meta-analysis. According to analysis of the included studies, patients with COVID-19 had significantly low T/LH, FSH/LH, and SHBG levels and high levels of LH, and E2/T, but their levels of FT, FSH, PRL, E2, and progesterone were not affected. Publication bias was not found according to funnel plots and Egger’s regression and Begg’s rank correlation tests.ConclusionLow T/LH, FSH/LH, and SHBG serum levels and high LH, and E2/T levels may increase the risk of COVID-19. Additionally, the greater is the clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in T/LH, FSH/LH, and SHBG levels. COVID-19 may have unfavourable effects on gonadal functions, which should be taken seriously by clinicians. Routine monitoring of sex hormone levels might help clinicians to evaluate disease severity in patients with COVID-19.

The LH endocrine profile in gonadotropin-releasing hormone analogue cycles

Research question: What does the evolution of serum luteinizing hormone (LH) levels look like throughout the follicular phase of cycles in which gonadotrophins and gonadotropin-releasing hormone (GnRH) analogues in the context of ovarian stimulation for assisted reproduction technologies (ART) were used? Design: This was a retrospective, observational cohort study in a tertiary infertility clinic. 1303 patients aged between 18 and 43 years of age were included with a total of 2200 cycles for ART, using GnRH-analogues for pituitary down-regulation stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH). Follicular evolution of LH during ovarian stimulation in different treatment protocols was modeled as repeated measures. Results: LH evolution showed a significant decrease in antagonist/hMG cycles of 0.17 IU/L per day (95% CI [-0.20, −0.12]) and 0.26 IU/L per day in rec-FSH cycles (95% CI [-0.29, −0.22]). This decrease was significantly stronger in rec-FSH cycles than in hMG cycles (estimated difference of 0.09 IU/L per day, 95% CI [0.04, 0.15]). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (95% CI [0.01, 0.08]), while the increase of 0.01 IU/L per day in cycles with rec-FSH was not significant (95% CI [-0.08, 0.10]). Conclusion: Follicular evolution of LH during controlled ovarian stimulation differs between different GnRH analogue cycles. A statistically significant decrease in LH was shown in GnRH antagonist cycles being more pronounced with rec-FSH compared to hMG. This decrease in LH in antagonist cycles and the potential impact on estradiol levels and follicle growth needs further examination.

Evaluation of Marjoram Leaves (Oregano vulgar) as Feed Supplement on Quality of Semen in Awasian Pollination Rams.

This study aimed to evaluate the effect of Marjoram leaves (Oregano vulgar) as a feed supplement on sexual efficiency and semen quality in Awasian pollination rams. The study was conducted on ten rams in one of the private fields in the Babylon governorate. The rams were divided randomly into two groups. First group rams are regarded as a control group (group A) that feeds on exceptional concentric food for pollination rams. The second group consists of 5 rams (group B) provided with the same concentric food plus a supplement of 3 mg/kg of body weight of Oregano vulgar leaves (fresh) 3 times daily for 49 days before the pollination season (April and May). Semen samples were collected at the end of 49 days by artificial vagina to evaluate the volume of ejaculate, sperm number, concentration, motility, viability, and deformities, and to measure the sperm pleomorphic parameters of the head, nucleus, and acrosome. The antioxidant status of seminal plasma was evaluated by measuring superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC). ELISA tests were used on blood serum samples to measure the hormone levels of luteinizing hormone (LH), testosterone, and estrogen. The study demonstrated a significant increase in motility, the viability of sperm, and decreasing deformities. There was no significant variation in perimorphic parameters of the head, nucleus, and acrosome sperm after using the fresh leaves of Oregano vulgar as supplementation to Awasion sheep. However, there was an increase in the antioxidant enzymes (SOD, GPX, and TAC) in seminal plasma and an increase in LH, testosterone, and estrogen in the blood serum of experimental group B. These findings show that using fresh leaves of Oregano vulgar improved the sexual efficiency of pollinated rams and maintained the physiology and perimorphic parameters of semen and sperm.

Relationship between GnRH-induced LH increase profiles in the serum and vaginal mucus of Japanese Black beef cows.

This study aimed to investigate the relationship between increases in the luteinizing hormone (LH) profiles in the serum and vaginal mucus of cows induced by gonadotropin-releasing hormone (GnRH). Samples for LH determination were collected from Japanese Black beef cows during estrus, which was induced with a controlled internal progesterone-releasing device and the administration of cloprostenol immediately before GnRH administration and every 30 min from the start of GnRH administration until 6.5 h. The peak serum LH concentration was clearly identified at 2.5 h post-GnRH administration, with serum concentrations returning to near-pre-GnRH-administration values after 6.5 h, whereas the peak vaginal mucus LH concentration was identified 4.5 h after GnRH administration. These results indicate that the LH secretion peak in vaginal mucus appeared about 2 h after peak LH secretion in the serum.