Normal Luteinizing Hormone Levels Research Articles

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. The ovarian tumors had hormonal activity. The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats.

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p=.0278) and low INHB serum levels (p=.0130) were recorded after CT-HSCT, especially after myeloablative conditioning. The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.

Low LH level does not indicate poor IVF cycle outcomes with GnRh-a single trigger: a retrospective analysis

ObjectiveTo compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger.MethodsWe retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels (< 10 mIU/mL) group (experimental group, n = 51). And the efficacy of hCG retrigger on IVF/ICSI cycle outcomes in 10 patients with low LH levels after GnRH-a single trigger.ResultsThere were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles.ConclusionThe IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary.

P-451 Gonadal development and function after high-risk gonadotoxic treatment and immature testicular tissue banking

Abstract Study question What is the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function of pre- and pubertal boys? Summary answer There is a risk for impaired reproductive hormone levels after high-risk gonadotoxic treatment protocols, especially after conditioning therapy before hematopoietic stem cell transplantation. What is known already Experimental fertility preservation programs have been started to safeguard the future fertility of pre- and pubertal boys requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies on their gonadal development and function are rather limited. Study design, size, duration A two-center follow-up study, conducted between 2002 and 2020, evaluated the gonadal development and function of pre- and pubertal boys who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of a high-risk gonadotoxic treatment and the testicular biopsy procedure. Participants/materials, setting, methods A cohort of 60 pre- and pubertal boys without ongoing spermatogenesis and requiring HR-C/R or CT-HSCT were included. Exclusion criteria were testicular cancer diagnosis and hormonal substitution treatment. Testicular growth measured with a Prader orchidometer and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and inhibin B (INHB) were analyzed after treatment completion and compared between HR-C/R and CT-HSCT treatment protocols as well as between boys accepting TTB and those refusing TTB. Main results and the role of chance Of the 60 pre- and pubertal boys included, 26 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted by 39 boys and refused by 21 boys. Most boys were prepubertal at diagnosis (87%), at treatment completion (78%) and at TTB (79%). After 5.0 (1.0-11.0) years post-treatment, most patients had normal testicular volumes (86%) and normal LH (81%), FSH (81%), testosterone (70%) and INHB (65%) serum levels. Testicular growth (P = 0.3773), LH (P = 0.4844), FSH (P = 0.1613) and INHB (P = 0.2553) were not significantly different between the treatment groups, but significantly more abnormal testosterone serum levels (P = 0.0138) were recorded after CT-HSCT (43%) compared to HR-C/R (10%). TTB had no effect on testicular growth (P &amp;gt; 0.9999), LH (P = 0.7186), FSH (P &amp;gt; 0.9999) and INHB (P = 0.7074). A significant difference for testosterone was observed between the TTB groups (P = 0.0210), but no significant difference for testosterone or the other hormones was observed when comparing the effect of the biopsy procedure within each treatment group separately. The Spearman’s correlation test reveals a significant positive correlation between patients treated by CT-HSCT and patients having chosen for TTB (P &amp;lt; 0.001). In boys who underwent a hemi-orchiectomy or small biopsy, the volumes of the biopsied and contralateral non-biopsied testes were not significantly different (P &amp;gt; 0.9999). Limitations, reasons for caution This clinical follow-up study included a low patient number and the follow-up period was rather limited. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings. Wider implications of the findings A more accurate understanding of the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function will allow better counseling of patients interested in fertility preservation and optimize selection of patients eligible for fertility preservation. Trial registration number not applicable

Integrity of hypothalamic-pituitary-testicular axis in exceptional longevity.

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic–pituitary‐testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90–106 years. We found that 94% of men exhibited preserved hypothalamic–pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging‐related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic–pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.

Tamoxifen as Empirical Treatment in Males with Primary Infertility and Normal Gonadotropic Hormonal Levels: A Prospective Study

Background: One of the most commonly employed medical therapies for idiopathic male infertility are antiestrogens. Tamoxifen as estrogen receptor blockers have been used as empiric treatments for male infertility, acting through blocking estrogen receptor at the hypothalamus and pituitary levels and so preventing the important negative feedback of estrogens to the pituitary and hypothalamus as a result that leading to gonadotropin releasing hormone (GnRH) stimulation and pulsatile release of luteinizing hormone (LH)/follicle-stimulating hormone (FSH). Objective: To assess tamoxifen role in the treatment of men with primary infertility who are normogonadotropic. as it is widely prescribed drug for that purpose as well as to evaluate possible patient’s criteria for a better response to tamoxifen. Methods: One hundred twenty-three patients with idiopathic primary infertility and normal FSH, LH, and testosterone serum levels were enrolled in this prospective study. All patients received 20 mg tamoxifen daily as a single dose for at least 3 months, and semen analysis (total sperm concentration, total number of progressive motile sperms and percentage of normal sperm morphology) as well hormones levels were evaluated, with the values being compared with those before treatment. Results: Overall, there was no statistically-significant improvement in semen parameters 3 months after treatment (P&gt;0.05); however, patients with pretreatment lower normal FSH level of (1.7-6.85 mIU/ml) and those with pretreatment sperm concentration of (five to ten million per ml) showed statistically significant improvement in sperm concentration after tamoxifen therapy (p=0.044 and p=0.012 respectively). Conclusion: Tamoxifen is an acceptable treatment for idiopathic male infertility. A better response can be expected in patients with pretreatment lower normal FSH level of (1.7-6.85 miu/ml) and sperm concentration of 5-10 million per ml. It might be used as first line treatment to enhance sperm concentration, giving its availability and lower cost in comparison to other hormonal therapies. Keywords: Male Infertility, tamoxifen, empirical treatment Citation: Al-Anbary LA. Tamoxifen as empirical treatment in males with primary infertility and normal gonadotropic hormonal levels: A prospective study. Iraqi JMS. 2021; 19(2): 230-236. doi: 10.22578/IJMS.19.2.12

Functions of Lysosomes in Mammalian Female Reproductive System

The lysosome is the most acidic membrane-bound intracellular organelle. Lysosomal acidity is primarily maintained by vacuolar H+-ATPase (V-ATPase) and counter ion channels. There are >60 hydrolytic enzymes in the lysosome for its fundamental digestive role. Lysosomes also play important roles in endocytosis, exocytosis, autophagy, and cell death. Studies that have implicated roles of lysosomes in the female reproductive system are reviewed here. In the ovary, lysosomes are implicated in the preparation of free cholesterol for steroidogenesis and degradation of regulators of steroidogenesis, regulation of follicular atresia, follicle rupture during ovulation, luteal cell survival, and luteal regression. In the oviduct, lysosomes are involved in endocytosis of both serum and oviductal luminal components. In the uterus during the menstrual/estrous cycle, lysosomes are associated with endometrial secretion, apoptosis, and menstruation. In the uterus during early pregnancy, lysosomes are involved in the temporal and directional changes of endocytosis, uterine epithelial acidification upon embryo implantation initiation, and embryo-maternal mutual communications via extracellular vesicles. In the placenta, lysosomes are implicated in nutrient transport and placental separation from the uterus for parturition. In the mammary gland, lysosomes are important for mammary gland development and involution. These findings suggest/demonstrate functions of lysosomes in multiple processes of female reproduction, from ovulation to ovarian steroidogenesis for pregnancy maintenance, and from essential in utero nurturing of developing embryos/fetuses via embryo/fetal-maternal communications, to optional postpartum nurturing of newborns via lactation. Future studies using genetically or modified animal models and pharmacological approaches will provide novel insights into the functions and mechanisms of lysosomes in the mammalian female reproductive system.

The prevalence of hypogonadism in men with type 2 diabetes mellitus in clinical practice

BACKGROUND: Hypogonadism is a common complication in men with type 2 diabetes mellitus (DM), but its prevalence remains unknown.&#x0D; AIMS: To estimate the prevalence of hypogonadism in men with type 2 DM.&#x0D; MATERIALS AND METHODS: Male patients with type 2 DM were enrolled into a single-cohort contemporaneous multicenter non-interventional screening study. The study period was from November 2017 through August 2018. Assessments included total testosterone, luteinizing hormone (LH), sex hormone-binding globulin, HbA1c levels. Levels of free testosterone were calculated by Vermeullen method.&#x0D; RESULTS: TheThe median of age of 400 included men was 56 years [51; 58], total testosterone was 12.3 [9.2; 16.5] nmol/l, free testosterone 270 [217; 334] pmol/l, HbA1c 7,1% [6.1; 8.6]. Hypogonadism was found in 135 men (33.7%). The total testosterone level in that group was 7.9 [6.8; 9.8] nmol/l, and free testosterone 192 [164; 227] pmol/l. In hypogonadism-free men their levels were 15,1 [12,4; 18,6] nmol/l and 311 [270; 364] pmol/l, respectively. In most patients with hypogonadism LH level was low, but within normal ranges, and significantly lower than in men without hypogonadism 3.2 [2.1; 4.7] IU/L vs 3.8 [2.7; 4.9] IU/L, respectively (p=0.007). Most commonly hypogonadism was with normal LH levels (92,6%, median LH level 3.2 [2.2; 4.3] IU/L, p0,001). The frequency of hypogonadism with high LH level (10.2 [9.2; 14.7] IU/L) and low LH level (1.0 [0.6; 1.1] IU/L) was 4.4% and 3.0%, respectively.&#x0D; CONCLUSIONS: The prevalence of hypogonadism in men with type 2 DM was found to be 33.7%. Normal levels of LH are typical for this type of patients with hypogonadism.

Kisspeptin in the Hypothalamus of 2 Rat Models of Polycystic Ovary Syndrome.

Hyperandrogenism, disturbance of the hypothalamus-pituitary-ovary axis followed by elevated serum luteinizing hormone (LH) levels, and insulin resistance are involved in the complicated pathophysiology of polycystic ovary syndrome (PCOS). Kisspeptin is coexpressed with neurokinin B (NKB) in the arcuate nucleus (ARC), the center of the gonadotropin-releasing hormone pulse generator that is responsible for pulsatile LH secretion. We compared 2 androgenized rat models of PCOS to evaluate the estrous cycle, hormonal profiles, and expression of kisspeptin and NKB in the ARC. Rats in our postnatal dihydrotestosterone (DHT)-treatment model exhibited weight gain and persistent diestrus with normal LH levels. In contrast, irregular cycles, with elevated LH serum levels and normal body weight, were found in the prenatally DHT-treated rats. We also found increased signals of kisspeptin and NKB in the ARC of the prenatally DHT-treated rats, and not in the postnatally DHT-treated rats. Our results suggest that prenatal exposure to androgens may result in higher kisspeptin and NKB levels in the ARC, which could be associated with 1 phenotype of PCOS that is characterized by normal body weight and higher LH secretion, whereas in postnatally DHT-treated rats, characteristics such as weight gain and normal LH levels are seen in the obese PCOS phenotype.

Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer

Objective: The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients.Materials and methods: Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1–73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7–89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6–42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation.Results: After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (< 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone >50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan–Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5–22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6–39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029).Conclusions: Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation.

To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation. In a prospective study, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and prolactin (PRL) of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD). male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p < 0.05), whereas E2 and PRL normalized (p < 0.05). The MELD score did not influence changes in FSH, PRL and LH, however, the more severe the cirrhosis was, the more significant was the normalization of E2 (p = 0.01). Patients with cirrhosis and male hypogonadism have inappropriately normal levels of FSH and LH, associated with an increase in E2 and LRP. After liver transplantation, FSH and LH increased, while E2 and PRL returned to normal. Changes in E2 levels were most pronounced in patients with MELD > 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

Kisspeptin cell-specific PI3K signaling regulates hypothalamic kisspeptin expression and participates in the regulation of female fertility.

Hypothalamic kisspeptin neurons integrate and translate cues from the internal and external environments that regulate gonadotropin-releasing hormone (GnRH) secretion and maintain fertility in mammals. However, the intracellular signaling pathways utilized to translate such information into changes in kisspeptin expression, release, and ultimately activation of the kisspeptin-receptive GnRH network have not yet been identified. PI3K is an important signaling node common to many peripheral factors known to regulate kisspeptin expression and GnRH release. We investigated whether PI3K signaling regulates hypothalamic kisspeptin expression, pubertal development, and adult fertility in mice. We generated mice with a kisspeptin cell-specific deletion of the PI3K catalytic subunits p110α and p110β (kiss-p110α/β-KO). Using in situ hybridization, we examined Kiss1 mRNA expression in gonad-intact, gonadectomized (Gdx), and Gdx + steroid-replaced mice. Kiss1 cell number in the anteroventral periventricular hypothalamus (AVPV) was significantly reduced in intact females but not in males. In contrast, compared with WT and regardless of steroid hormone status, Kiss1 cell number was lower in the arcuate (ARC) of kiss-p110α/β-KO males, but it was unaffected in females. Both intact Kiss-p110α/β-KO males and females had reduced ARC kisspeptin-immunoreactive (IR) fibers compared with WT animals. Adult kiss-p110α/β-KO males had significantly lower circulating luteinizing hormone (LH) levels, whereas pubertal development and fertility were unaffected in males. Kiss-p110α/β-KO females exhibited a reduction in fertility despite normal pubertal development, LH levels, and estrous cyclicity. Our data show that PI3K signaling is important for the regulation of hypothalamic kisspeptin expression and contributes to normal fertility in females.

Gitelman syndrome manifesting in early childhood and leading to delayed puberty: a case report

IntroductionGitelman syndrome is an inherited autosomal recessive renal salt-wasting disorder. It presents with variable clinical symptoms including muscle weakness and fatigue, and the diagnosis is based on metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria. It is usually diagnosed incidentally in early adulthood. There are rare cases of Gitelman syndrome presenting in early childhood; however, to the best of our knowledge it has not previously been associated with delayed puberty.Case presentationA 17-year-old South Asian man with recurrent episodes of generalized muscle weakness, fatigue and cramps from the age of two years was admitted for further workup. Before the age of 12 years, the episodes had been mild, but they then got progressively worse. Other symptoms include polyuria, polydipsia, nocturia, paresthesia and occasional watery diarrhea. He also had a history of short stature, poor weight gain and delayed developmental landmarks. His family history was unremarkable except for the consanguineous marriage of his parents. An examination revealed a thin and lean man with blood pressure of 95/60mmHg. His height and weight were below the third percentile and his sexual development was at Tanner Stage II. Laboratory work revealed serum sodium of 124mmol/L, potassium 2.4mmol/L, calcium 6.5mmol/L and magnesium of 1.2mg/dL. His testosterone level was low (0.85ng/mL, normal for his age 2.67 to 10.12ng/mL) with normal levels of luteinizing hormone and follicle-stimulating hormone. The sex hormone findings were attributed to delayed puberty. A 24-hour urinary analysis revealed decreased excretion of calcium (25.9mg/24 hours). Based on the findings of hypokalemic metabolic alkalosis without hypertension, severe hypomagnesemia and hypocalciuria, a diagnosis of Gitelman syndrome was made. Treatment was started with oral supplementation of potassium, magnesium and calcium along with spironolactone and liberal salt intake.ConclusionDiagnosis of Gitelman syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. We report that Gitelman syndrome can present during the early childhood years. If undiagnosed and untreated, it can lead to growth retardation and delayed puberty.

Changes in the Plasma Sex Hormone Profile in Males with Severe Concomitant Injury

Objective: to perform a complex study of typical plasma sex hormone changes and their functional significance in males with severe concomitant injury (SCI). Subjects and methods. Fifty-nine males aged 18—49 years who had SCI were enrolled in the study. The admission severity was an APACHE II score of 18.6±2.4. According to the outcome of the disease, all the patients were divided into 2 groups: A) survivors; B) deceased persons. A control comprised 12 healthy male donors aged 19-36 years, in whom the levels of 8 sex steroids were measured. The standard procedures were used to comparatively analyze the concentrations of pituitary reproductive hormones and aldosterone. Hormonal concentrations were studied over time on posttraumatic days 1, 3, 5, 7, 10, and 15. The plasma hormone profile was examined by test kits (BSL, USA) on a Stat Fax 2100 device (Awareness Technology Inc., USA) for enzyme immunoassay. Prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P), 17-hydroxyprogesterone (17-OH-P), dehydroepiandrosterone sulfate (DHEA-S), androstendione (A), testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2), and aldosterone were determined. Results. The complex study of phasic changes in the profile of 11 plasma sex hormones was first conducted in males in the posttraumatic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels and their phasic variations, normal LH and FSH levels with a tendency for further phasic LH changes and FSH reduction. After the injury, the plasma concentration of P was increased and that of 17-OH-P was decreased. The levels of A and DHEA-S varied in the normal range with a tendency for DHEA-S to be lower during the process. In the posttraumatic period, the plasma content of T and DHT was substantially reduced and that of E1 and E2 was increased. The deceased patients generally showed higher levels of A, DHEA-S, and estrogens as a reflection of dysregulatory pathology and complications. The changes revealed in hormonal levels are of significance in understanding the pathogenesis of SCT and its sequels. This may serve as a basis for the development of new therapy methods using sex hormones as adaptogens in the postresuscitative period. Key words: severe concomitant injury, sex hormones, prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, androgens, estrogens.

Long‐term effects of a short course of neoadjuvant luteinizing hormone‐releasing hormone analogue and radical radiotherapy on the hormonal profile in patients with localized prostate cancer

To assess whether a long-term follow-up shows any reduction in the level of luteinizing hormone (LH) secretion, which could result in declining testosterone levels in men with localized prostate cancer, as most (96%) men have testosterone levels within the normal range by 1 year after treatment with a short course of LH-releasing hormone analogue (LHRHa) and radiotherapy, and LH and follicle stimulating hormone (FSH) remain high at 1 year after treatment, maintaining the testosterone levels. We prospectively evaluated 55 patients who previously had a short course of LHRHa (median 97 days, range 28-167) and radiotherapy for localized prostate cancer. Eligible patients had documented normal testosterone, LH and FSH levels at baseline and at 1-3 years after radiotherapy. LH, FSH and testosterone were then measured at 5 years after treatment. The mean hormone levels before, at 1-3 years and at 5 years after treatment, respectively, were: testosterone (nmol/L), 15.33, 13.98, 12.97; LH (U/L), 5.51, 9.95, 6.95; and FSH (U/L), 7.95, 22.40, 17.00. The decrease in testosterone level at 5 years vs 1-3 years was not statistically significant and was of little clinical relevance (P = 0.057). LH and FSH levels were higher at 1-3 years than at baseline and decreased significantly (P < 0.001) at 5 years towards the baseline value. The decrease in FSH level was less marked than for LH. After a short course of LHRHa and radiotherapy, the testosterone level was maintained at 5 years. LH levels decreased towards the baseline value, suggesting recovery of Leydig cell function. FSH levels remained high, suggesting persistent Sertoli cell damage from treatment.

Hypogonadism in HIV-1-Infected Men is common and does not resolve during antiretroviral therapy

To assess the prevalence of abnormal testosterone and gonadotropin values in HIV-infected men before and after 2 years of combination antiretroviral therapy (cART). Multicentre cohort of HIV-infected adults. We identified 139 Caucasian antiretroviral-naive male patients who started zidovudine/ lamivudine-based cART that was virologically successful over a 2 year period. Ninety-seven were randomly chosen and plasma hormone determinations of free testosterone (fT) and luteinizing hormone (LH) at baseline and after 2 years of cART were evaluated. At baseline 68 patients (70%) had subnormal fT levels. In these, LH levels were low in 44%, normal in 47% and high in 9%. There was a trend for an association between lower CD4+ T-cell counts and hypogonadism. Most participants had normal FSH levels. No significant changes of fT, LH and FSH levels were observed after 2 years of cART. Low fT levels, mainly with normal or low LH levels and thus indicating secondary hypogonadism, are found in the majority of HIV-infected men and do not resolve during 2 years of successful cART.

A Novel Androgen Receptor Mutation Resulting in Complete Androgen Insensitivity Syndrome and Bilateral Leydig Cell Hyperplasia

Androgens drive male secondary sexual differentiation and maturation. Mutations in the androgen receptor (AR) gene cause a broad spectrum of abnormal phenotypes in humans, ranging from mild through partial to complete androgen insensitivity. We have analyzed the AR gene by using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing and have studied gonads histologically in a familial case of complete androgen insensitivity syndrome. Sequence analysis of the AR gene showed a novel C2578T missense mutation, resulting in the replacement of a highly conserved leucine residue with phenylalanine (L859F) in ligand-binding domain of the receptor. The residue L859, located in helix 10 of the androgen receptor, plays a significant role in overall architecture of ligand-binding pocket. The mutation was absent from the father, normal brother of the patients, and 100 normal males recruited in this study as controls. The inheritance of the mutation in the family clearly shows that C2578T is the underlying mutation for the eventual phenotype in the patients. Histology of patient's gonads showed Leydig cell hyperplasia, with a few or no spermatogonium. It is thought that AR gene mutations result in hormonal imbalance, resulting in the high levels of luteinizing hormone (LH) and ultimately Leydig cell hyperplasia or tumor formation. In the present study, we have reported a rare familial case of Leydig cell hyperplasia despite consistently normal LH levels. The finding will help in giving counseling to this family and prevent the transmission of the mutated X chromosome to the coming generations.

Galanin-Like Peptide Rescues Reproductive Function in the Diabetic Rat

Galanin-like peptide (GALP) is expressed in the hypothalamic arcuate nucleus and is regulated by leptin and insulin. Centrally administered GALP stimulates gonadotropin secretion and sexual behavior in the rat. Type 1 diabetes is associated with reduced expression of GALP, as well as an overall decline in reproductive function. We postulated that tonic activity of GALP in the brain is required to sustain normal reproductive activity. To test this hypothesis, we examined whether central (intracerebroventricular) immunoblockade of GALP would reduce sexual behaviors and serum levels of luteinizing hormone (LH) in normal adult male rats. We found that GALP antibody reversibly reduced serum levels of LH and abolished male sexual behaviors (P < 0.05 and 0.001, respectively). Second, we tested whether intracerebroventricular GALP could restore normal plasma LH levels and sexual behavior in diabetic animals. We compared groups of diabetic rats that received intracerebroventricular GALP or vehicle and found that GALP increased serum levels of LH and sexual behavior. Third, we examined whether intracerebroventricular administration of affinity-purified GALP antibody could block the effect of insulin and leptin in reversing the effects of diabetes on LH and sexual behavior. We found that treatment of diabetic animals with insulin and leptin nearly normalized LH levels and sexual behaviors; however, this effect was attenuated by intracerebroventricular administration of GALP antibody (P < 0.05). These observations demonstrate that endogenous GALP provides trophic support to the neuroendocrine reproductive axis, including sexual behavior.

Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague–Dawley rats 35 days old were pair-fed a Lieber–DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.