Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by Exogenous Gonadotropins

Abstract Circulating leptin shows a pulsatile secretory pattern along with a nocturnal rise. We have previously shown that circulating leptin concentrations are high in males with untreated idiopathic hypogonadotropic hypogonadism (IHH). However, circadian leptin secretion in IHH before and after gonadotropin treatment is not known. Thus, we studied 14 adult males with IHH who had no history of previous hormonal therapy, and 12 age- and body mass index-matched healthy men. Plasma leptin concentrations were measured with 1-h intervals for 24 h before and 6 months after gonadotropin treatment. The 24-h mean leptin concentration showed a significant decrease, from 11.78 ± 1.908 μg/liter at baseline to 10.85 ± 1.939 μg/liter after 6 months of therapy (z = 3.107; P = 0.002). Before and after treatment, 24-h mean leptin concentrations were also significantly higher in the patient group when compared with controls (4.275 ± 0.711 μg/liter) (z = 5.938; P = 0.0001). Hourly leptin levels demonstrated a diurnal pattern in hypogonadal patients, a surge in the midday, and a peak just after midnight, and this pattern did not differ before and after treatment. We observed a similar diurnal pattern in the control subjects too. Leptin levels were negatively and significantly correlated with free testosterone and total testosterone levels both before (r = −0.656, P = 0.011; and r = −0.639, P = 0.014, respectively) and after (r = −0.537, P = 0.048; and r = −0.563, P = 0.036, respectively) gonadotropin administration. Our observations suggest that the diurnal rhythm of leptin is intact in males with IHH, and short-term gonadotropin treatment does not effect its diurnal rhythm. Moreover, testosterone produced under the influence of the gonadotropin treatment led to decreases in the leptin levels.

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Effects of heavy-resistance training on hormonal response patterns in younger vs. older men

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.3.982 ◽

1999 ◽

Vol 87 (3) ◽

pp. 982-992 ◽

Cited By ~ 247

Author(s):

William J. Kraemer ◽

Keijo Häkkinen ◽

Robert U. Newton ◽

Bradley C. Nindl ◽

Jeff S. Volek ◽

...

Keyword(s):

Resistance Training ◽

Training Program ◽

Free Testosterone ◽

Older Men ◽

Total Testosterone ◽

Igf I ◽

Before And After ◽

Igf Binding ◽

Heavy Resistance Training ◽

Igf Binding Protein

To examine the adaptations of the endocrine system to heavy-resistance training in younger vs. older men, two groups of men (30 and 62 yr old) participated in a 10-wk periodized strength-power training program. Blood was obtained before, immediately after, and 5, 15, and 30 min after exercise at rest before and after training and at rest at −3, 0, 6, and 10 wk for analysis of total testosterone, free testosterone, cortisol, growth hormone, lactate, and ACTH analysis. Resting values for insulin-like growth factor (IGF)-I and IGF-binding protein-3 were determined before and after training. A heavy-resistance exercise test was used to evaluate the exercise-induced responses (4 sets of 10-repetition maximum squats with 90 s of rest between sets). Squat strength and thigh muscle cross-sectional area increased for both groups. The younger group demonstrated higher total and free testosterone and IGF-I than the older men, training-induced increases in free testosterone at rest and with exercise, and increases in resting IGF-binding protein-3. With training the older group demonstrated a significant increase in total testosterone in response to exercise stress along with significant decreases in resting cortisol. These data indicate that older men do respond with an enhanced hormonal profile in the early phase of a resistance training program, but the response is different from that of younger men.

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Testosterone and its binding in hyperthyroid women before and under antithyroid drug therapy

Acta Endocrinologica ◽

10.1530/acta.0.1210443 ◽

1989 ◽

Vol 121 (3) ◽

pp. 443-446 ◽

Cited By ~ 1

Author(s):

Sylvain Loric ◽

Françoise Duron ◽

Jérôme Guéchot ◽

Pierre Aubert ◽

Jacqueline Giboudeau

Keyword(s):

Drug Therapy ◽

Antithyroid Drug ◽

Free Testosterone ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Hormone Binding ◽

Antithyroid Drug Therapy ◽

Before And After ◽

Hyperthyroid Patients

Abstract. The serum concentrations of the different forms of circulating testosterone, total testosterone, free testosterone and non-sex-hormone binding globulin bound testosterone (albumin bound + free fractions) which is considered as the biovailable hormone, were measured in 15 hyperthyroid women before and after anti-thyroid drug therapy and in 15 age-matched healthy women. Sex-hormone binding globulin and albumin were quantified. Total testosterone was significantly higher in hyperthyroid women before treatment, whereas free testosterone and non sex-hormone binding globulin bound testosterone were significantly decreased. After recovery, all the parameters returned to the normal range. In hyperthyroid patients, the variations in the different fractions of testosterone can be related to the rise of sex-hormone binding globulin. These variations could be explained by the displacement of the equilibrium defined by the binding equation.

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Changes in Testosterone Levels and Sex Hormone-Binding Globulin Levels in Extremely Obese Men after Bariatric Surgery

International Journal of Endocrinology ◽

10.1155/2016/1416503 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 17

Author(s):

Patchaya Boonchaya-anant ◽

Nitchakarn Laichuthai ◽

Preaw Suwannasrisuk ◽

Natnicha Houngngam ◽

Suthep Udomsawaengsup ◽

...

Keyword(s):

Bariatric Surgery ◽

Hypogonadotropic Hypogonadism ◽

Free Testosterone ◽

Serum Levels ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Morbidly Obese ◽

The Mean ◽

A Prospective Study ◽

Estradiol Levels

Objective.Obesity is a risk factor for hypogonadotropic hypogonadism in men. Weight loss has been shown to improve hypogonadism in obese men. This study evaluated the early changes in sex hormones profile after bariatric surgery.Methods.This is a prospective study including 29 morbidly obese men. Main outcomes were changes in serum levels of total testosterone (TT), free testosterone (cFT), SHBG, estradiol, adiponectin, and leptin at 1 and 6 months after surgery.Results.The mean age of patients was 31 ± 8 years and the mean BMI was 56.8 ± 11.7 kg/m2. Fifteen patients underwent Roux-en-Y gastric bypass and 14 patients underwent sleeve gastrectomy. At baseline, 22 patients (75.9%) had either low TT levels (<10.4 nmol/L) or low cFT levels (<225 pmol/L). Total testosterone and SHBG levels increased significantly at 1 month after surgery (p≤0.001). At 6 months after surgery, TT and cFT increased significantly (p≤0.001) and 22 patients (75.9%) had normalized TT and cFT levels. There were no changes in estradiol levels at either 1 month or 6 months after surgery.Conclusions. Increases in TT and SHBG levels occurred early at 1 month after bariatric surgery while improvements in cFT levels were observed at 6 months after bariatric surgery.

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Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism

Acta Endocrinologica ◽

10.1530/eje-07-0663 ◽

2008 ◽

Vol 158 (5) ◽

pp. 741-747 ◽

Cited By ~ 78

Author(s):

Sandra Loves ◽

Janneke Ruinemans-Koerts ◽

Hans de Boer

Keyword(s):

Hypogonadotropic Hypogonadism ◽

Serum Testosterone ◽

Free Testosterone ◽

Total Testosterone ◽

Male Hypogonadism ◽

Serum Lh ◽

Long Term Effect ◽

Starting Dose ◽

Severely Obese ◽

Lh Secretion

ObjectiveIsolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E2) production and E2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.DesignOpen, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m2) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.ResultsSix weeks of treatment reduced total E2 from 123±11 to 58±7 pmol/l (P<0.001, mean±s.e.m.), and increased serum LH from 4.4±0.6 to 11.1±1.5 U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4 nmol/l (P<0.001), and free testosterone from 163±13 to 604±50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E2 levels were stable throughout the week and during the 6-month treatment period.ConclusionLetrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.

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FC11-05 - Hormonal profile in depressed and non-depressed perimenopausal women

European Psychiatry ◽

10.1016/s0924-9338(11)73578-7 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1874-1874

Author(s):

M. Flores-Ramos ◽

I. Méndez Ramírez

Keyword(s):

Depressive Episode ◽

Post Partum ◽

Follicle Stimulating Hormone ◽

Free Testosterone ◽

Serum Levels ◽

Total Testosterone ◽

Recurrent Depression ◽

Post Partum Depression ◽

Perimenopausal Women ◽

History Of

ObjectiveTo determine if serum levels of Follicle Stimulating Hormone, Luteinizing Hormone, estradiol, progesterone, Free Testosterone and Total Testosterone differ between perimenopausal women with first depressive episode, recurrent depression and without depression.MethodsDemographic and clinical characteristics were evaluated in 63 perimenopausal women with first depressive episode (N = 20), recurrent depression (N = 23) or non-depressed (N = 20). Hormonal measurements were evaluated at follicular and luteal menstrual phases and mid-cycle, around one menstrual cycle.ResultsWhen compared depressed and non-depressed women we observed lower levels of luteal progesterone, higher levels of total testosterone and an increasing level of FSH in depressed patients. Differences between the three groups were observed in luteal progesterone levels, luteal FT, and luteal TT. Independently of current diagnosis, women with and without pmdd antecedent, differed in progesterone and testosterone levels. We did not find association of perimenopausal depression and history of post partum depression.ConclusionsHormonal profiles differed between groups. Patients with antecedent of pmdd had a similar progesterone and testosterone profile to perimenopausal depressed women.

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SAT-LB5 Prevalence of Hypogonadism in Young Obese Males

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2021 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Anup Halappanavar ◽

Rajiv Pakhetra

Keyword(s):

Hypogonadotropic Hypogonadism ◽

Armed Forces ◽

Free Testosterone ◽

Sex Hormone Binding Globulin ◽

P Value ◽

Total Testosterone ◽

Reference Ranges ◽

Cross Sectional ◽

Testosterone Levels ◽

The Impact

Abstract Ageing, obesity, and chronic illness are major factors affecting serum testosterone (T) levels in men.The magnitude of the impact of ageing on serum T levels is well established, for obesity this is less clear. Severe obesity may lead to isolated hypogonadotropic hypogonadism (IHH). Several explanations have been offered to clarify the presence of reduced T levels in obese men. One relates to the technique that is generally employed to measure serum androgen levels, i.e. measurement of total testosterone (TT) instead of free testosterone (FT). TT represents the sum of FT and T bound to albumin and sex hormone binding globulin (SHBG). A profound reduction in SHBG level is commonly found in obese men, and this is a major factor causing a decrease in TT.Measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range. However, reference ranges for free testosterone levels are not well established, especially in older men, and some have argued that the measurement of free testosterone levels merely reintroduces age in a covert form. This is a cross sectional study to estimate prevalence of hypogonadism in young obese males. In this study 147 young obese men participated, of which we confirmed low total testosterone (TT) levels in 35.37% of subjects with a p value of 0.06. Since only Total Testosterone was measured for categorizing subjects with or without hypogonadism, Free Testosterone measurement would be a better indicator for the diagnosis of hypogonadism as in cases where the total testosterone is borderline-low or when SHBG concentrations are abnormal. As such, the study is valuable in the context of the ongoing controversy as to whether testosterone treatment should be limited to men with classical hypogonadism, or be considered for appropriately selected men with functional hypogonadism as well. The principal findings are in general agreement with existing literature reporting correlation between levels of testosterone, body mass index and constitutional symptoms. However, this has never been shown before in context of Indian population. The present study was carried out at Armed Forces Medical College and Command Hospital, Pune between October 2017 to August 2019.We studied to see if there is association between testosterone levels and BMI. In our study we found no statistical association as the p value was 0.26 (>0.05)

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SAT-210 When Acne, Hirsutism and Menstrual Irregularities Are More Than PCOS

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1067 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Paola Rios ◽

Gabriela Zuniga ◽

Alex Manzano

Keyword(s):

Genetic Counseling ◽

Hair Loss ◽

Molecular Genetic ◽

Free Testosterone ◽

Molecular Genetic Analysis ◽

Total Testosterone ◽

Cyp21a2 Gene ◽

History Of ◽

Common Deficiency ◽

Ovarian Syndrome

Abstract Background: Polycystic ovarian syndrome (PCOS) mimics non-classic congenital hyperplasia (NCCAH), presenting with hyperandrogenic symptoms. NCCAH is usually diagnosed later in life, where 21-hydroxylase (21OHD) is the most common deficiency. There are more than 300 mutations in 21OHD, being V281L one of the described mutations. Clinical Case: 23 y/o female patient G0P0 comes to the office complaining of irregular periods, frontal hair loss, weight gain, acne and hirsutism. She has had noticed these changes since menarche; however, her acne was getting worse. Was seen 2 months prior to presentation by her gynecologist who order a free Testosterone that was elevated (6.4 pg/mL, n<4.2 pg/mL), with normal TSH (1.1 uIU/mL, n,0.45-4.5). She was not taking any medication. Her mother has history of 2 spontaneous abortions and her sister has acne and hirsutism as well. On physical exam BMI was 26, it was noticed comedones and papules on her face, back and shoulders. Ferriman-Gallwey scale was >8. At the initial visit due to the clinical scenario, it was thought that she had hyperandrogenic syndrome, probably secondary to PCOS. Serum blood test were ordered and showed an elevated total testosterone (71 ng/dL, n,8-48ng/dL), free testosterone (8.4 pg/mL, n<4.2 pg/mL), 17- OH pregnenolone performed by liquid chromatography-tendem mass spectrometry (LC-MS/MS) was (429 ng/dL, n, 35-290 ng/dL luteal phase) and androstenedione LC-MS/MS (1941 ng/dL, n, 41-262 ng/dL) which confirmed NCCAH diagnosis due to 21OHD. She had no desire to become pregnant at the time of evaluation; however, was concern about fertility and genetics. Was started on OCPs and genetic testing was positive for V281L mutation in the CYP21A2 gene, being homozygous for this mutation. Three months after, her acne and frontal hair loss were better, and a trial of spironolactone 50 mg daily, was prescribed. For her sister and mother was suggested to consult endocrinology, due to possible same disease. Conclusion: this case highlights the importance of recognizing NCCAH as a cause of hyperandrogenism. Molecular genetic analysis should be offered with genetic counseling to patients, since they can carry a severe allele which can affect their progeny. Clinicians should be aware of the importance of family history when diagnosing NCCAH on their patients; for detection, treatment and genetic counseling of NCCAH on family members as well, as found in this case.

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Vitamin D and Male Sexual Function: A Transversal and Longitudinal Study

International Journal of Endocrinology ◽

10.1155/2018/3720813 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Giacomo Tirabassi ◽

Maurizio Sudano ◽

Gianmaria Salvio ◽

Melissa Cutini ◽

Giovanna Muscogiuri ◽

...

Keyword(s):

Vitamin D ◽

Logistic Regression ◽

Sexual Function ◽

Replacement Therapy ◽

Erectile Function ◽

Free Testosterone ◽

Total Testosterone ◽

Logistic Regression Models ◽

Before And After ◽

Male Sexual Function

Background. The effects of vitamin D on sexual function are very unclear. Therefore, we aimed at evaluating the possible association between vitamin D and sexual function and at assessing the influence of vitamin D administration on sexual function. Methods. We retrospectively studied 114 men by evaluating clinical, biochemical, and sexual parameters. A subsample (n=41) was also studied longitudinally before and after vitamin D replacement therapy. Results. In the whole sample, after performing logistic regression models, higher levels of 25(OH) vitamin D were significantly associated with high values of total testosterone and of all the International Index of Erectile Function (IIEF) questionnaire parameters. On the other hand, higher levels of total testosterone were positively and significantly associated with high levels of erectile function and IIEF total score. After vitamin D replacement therapy, total and free testosterone increased and erectile function improved, whereas other sexual parameters did not change significantly. At logistic regression analysis, higher levels of vitamin D increase (Δ-) were significantly associated with high values of Δ-erectile function after adjustment for Δ-testosterone. Conclusions. Vitamin D is important for the wellness of male sexual function, and vitamin D administration improves sexual function.

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A Case of TSH-Secreting Pituitary Adenoma With Unusual Positive Staining for SF1

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1861 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A911-A912

Author(s):

Kathleen Robinson ◽

Brian O’Neill

Keyword(s):

Stem Cell ◽

Pituitary Adenoma ◽

Rare Case ◽

Hypogonadotropic Hypogonadism ◽

Stem Cell Population ◽

Total Testosterone ◽

Positive Staining ◽

Suprasellar Region ◽

History Of

Abstract Background: TSH-secreting pituitary adenomas are the rarest functional pituitary tumors. While they are often plurihormonal, SF1 positivity (indicating gonadotroph lineage) is unusual. Here we present the rare case of a patient with TSH-secreting pituitary adenoma with staining positive for TSH, GH, prolactin, SSTR2A, PIT-1, and SF1. Clinical Case: Patient is a 42 year-old male with a history of hypogonadotropic hypogonadism (lost to follow-up), who presented with a 5 day history of nausea and vomiting. Vitals were notable for tachycardia to 108 BPM, with BMI 14.8 kg/m2. On physical exam he had enlarged right hemi-thyroid and exophthalmos. Labs were notable for TSH 12.55 μIU/mL (0.27-4.20), Free T4 >7.77 ng/dL (0.80-1.80), Free T3 29.02 pg/mL (2.57-4.43), 8am cortisol 0.9 μg/dL (6.0-18.4), FSH 0.6 μIU/ml (1.5-12.4), LH 0.8 μIU/mL (1.7-8.6), PRL 8.5 ng/mL (4.0-15.2), total testosterone <5 ng/dL (249-836), and IGF-1 88.9 ng/mL (94.4-223.0). MRI showed large lobulated pituitary mass extending into the suprasellar region with mass effect and thyroid US showed enlarged almost completely cystic right hemi-thyroid. The patient was started on methimazole 30mg BID, prednisone 40mg daily, and cabergoline 0.5mg weekly (he declined octreotide). FT4 and FT3 remained significantly elevated despite escalation of cabergoline to 0.5mg 5 days weekly, so the patient was admitted two months after his initial presentation for plasmapheresis followed by thyroidectomy. His hospital course was complicated by post-op meningitis and DI, both successfully treated. Surgical pathology was notable for patchy expression of TSH with rare cells expressing GH and prolactin, SSTR2A positivity, strong nuclear positivity for PIT-1 with negative T-PIT staining, and unusual positivity for SF1. At follow-up he is clinically euthyroid and stable without use of LT4 or HC therapy. Repeat TSH, FT4, ACTH, cortisol, and testosterone are pending. He declines chemotherapy, radiation, and octreotide. Conclusion: This is a rare case of TSH-producing adenoma demonstrating SF1 positivity in addition to TSH, GH, PRL, and PIT-1 expression, in the absence of excess gonadotroph secretion. When such tumors secrete multiple hormones, this has been used as evidence to support the argument that such tumors arise from a stem cell population(1). However, the implications for our patient remain unclear. References: (1) Tordjman et al. Plurihormonal Pituitary Tumor of Pit-1 and SF-1 Lineages, with Synchronous Collision Corticotroph Tumor: a Possible Stem Cell Phenomenon. Endocr Pathol. 2019 Mar;30(1):74-80.

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