Hypogonadotropic hypogonadism in human immunodeficiency virus-infected men: uncommonly low testosterone levels

Summary Hypogonadotropic hypogonadism (HH) is common and occurs prematurely in HIV-infected men. However, HH with very low testosterone has not been described. Three men with normal pubertal development and HIV1 diagnosis at the ages of 22, 34 and 35 years. All complained of decreased libido, anejaculation and erectile dysfunction thirteen years, six months and one year after HIV diagnosis, respectively. Two had depressive syndrome and two were treated with antiretroviral therapy. Laboratory tests revealed isolated HH in all. Sellar and head CT scans were normal and all had normal CD4 count. They started testosterone replacement therapy, with symptoms improvement. Causes of HH in HIV-infected men include undernutrition, severe illness, drugs, pituitary dysfunction and comorbidities. Despite having none of these conditions (except two that were treated with low-dose psychotropics), our patients had HH with uncommonly low testosterone. This suggests that a different mechanism contributes to severe HH in HIV-infected men. Learning points: The pathogenesis of hypogonadotropic hypogonadism in HIV-infected men is multifactorial and androgen deficiency is more often a consequence of secondary hypogonadism than primary hypogonadism. Causes of hypogonadotropic hypogonadism in HIV-infected men include undernutrition, severe illness, drugs (psychotropics, opiates, megestrol acetate or steroids), pituitary dysfunction (tumor, hyperprolactinemia), an AIDS-related lesion (very rarely) and comorbid conditions, such as antibody to hepatitis C virus seropositivity and injection drug use. Highly active antiretroviral therapy (HAART), particularly protease inhibitor therapy has been associated with sexual dysfunction in men, but the causal nature of this relation has not been clearly established. Hypogonadotropic hypogonadism with uncommonly low testosterone levels are not usually associated with the conditions referred and this suggests that a different mechanism could contribute to severe hypogonadotropic hypogonadism in HIV-infected men. Screening for hypogonadism in all HIV-infected men might help to understand its etiology.

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Low testosterone is associated with disability in men with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514527864 ◽

2014 ◽

Vol 20 (12) ◽

pp. 1584-1592 ◽

Cited By ~ 52

Author(s):

R Bove ◽

A Musallam ◽

BC Healy ◽

K Raghavan ◽

BI Glanz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Hypogonadotropic Hypogonadism ◽

Total Testosterone ◽

Cross Sectional ◽

Testosterone Levels ◽

Vitamin D Levels ◽

Relapsing Remitting ◽

25 Hydroxy Vitamin D ◽

Male Patients ◽

Low Testosterone

Background: Gonadal steroids may modulate disease course in multiple sclerosis (MS). Objective: To assess the prevalence and clinical associations of hypogonadism in men with MS. Methods: Male patients, aged 18–65 years, with relapsing–remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually. Results: Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS ( p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT ( p = 0.012). Conclusions: Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.

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Cardiovascular and Cerebrovascular Safety of Testosterone Replacement Therapy Among Aging Men with Low Testosterone Levels: A Cohort Study

The American Journal of Medicine ◽

10.1016/j.amjmed.2019.03.022 ◽

2019 ◽

Vol 132 (9) ◽

pp. 1069-1077.e4 ◽

Cited By ~ 8

Author(s):

Simone Y. Loo ◽

Laurent Azoulay ◽

Rui Nie ◽

Sophie Dell’Aniello ◽

Oriana Hoi Yun Yu ◽

...

Keyword(s):

Cohort Study ◽

Replacement Therapy ◽

Testosterone Replacement ◽

Testosterone Replacement Therapy ◽

Testosterone Levels ◽

Aging Men ◽

Low Testosterone

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Anemia and HIV in the Antiretroviral Era: Potential Significance of Testosterone.

Blood ◽

10.1182/blood.v104.11.3722.3722 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3722-3722

Author(s):

Caroline M. Behler ◽

Starley B. Shade ◽

Kellan Gregory ◽

Donald I. Abrams ◽

Paul A. Volberding

Keyword(s):

Logistic Regression ◽

Antiretroviral Therapy ◽

Confidence Intervals ◽

Opportunistic Infections ◽

P Value ◽

Hiv Disease ◽

Odds Ratios ◽

Multivariable Logistic Regression Model ◽

Testosterone Levels ◽

Low Testosterone

Abstract BACKGROUND: Anemia remains the most common hematologic disorder in human immunodeficiency virus (HIV) infection despite the use of effective antiretroviral therapy, and is associated with decreased quality of life and survival. Hypogonadism is prevalent in advanced HIV disease, however low testosterone levels have not been customarily implicated in HIV-associated anemia. This study was undertaken to determine whether there is a relationship between testosterone levels and androgen use with anemia in HIV, and to characterize other clinical correlates of HIV-associated anemia. METHODS: This cross-sectional study examined the clinical characteristics of 200 HIV positive patients at a public hospital HIV clinic and clinical features associated with anemia. A written questionnaire detailed previous and current medication use, opportunistic infections and malignancies. Hematologic and virologic parameters, testosterone and erythropoietin levels were measured; CD4 count and viral load nadir and peak levels were obtained from the computerized medical record. Anemia was defined as hemoglobin <13.5 g/dL in men and <11.6 g/dL in women. RESULTS: Anemia was present in 24% of women and 28% of men. Anemia was negatively associated with female sex (adjusted OR 0.30, 95% CI 0.11–0.85), current antiretroviral therapy (adjusted OR 0.43, 95% CI 0.20–0.95), current androgen use (adjusted OR 0.20, 95% CI 0.05–0.84) and macrocytosis (adjusted OR 0.23, 95% CI 0.09–0.61). Anemia was positively associated with lymphopenia (adjusted OR 4.0, 95% CI 1.36–11.80), high erythropoieitin levels (adjusted OR 7.73, 95% CI 2.92–20.48) and low testosterone levels (adjusted OR 3.27, 95% CI 1.01–10.60). CONCLUSIONS: Low testosterone levels may have a positive association, and supplemental androgens a negative association with anemia in HIV disease. Predictors of Anemia Unadjusted odds ratios and 95% confidence intervals obtained by logistic regression. Variables that achieved a p-value of <0.1 in tests of interaction were included in a multivariable logistic regression model, which was used to obtain adjusted odds ratios and 95% confidence intervals. N % Anemic Unadjusted OR (95% CI) Adjusted OR (95% CI) Female 38 23.7 0.78 (0.34, 1.78) 0.30 (0.11, 0.85) Male/MTF Transgender 162 28.4 Lymphopenia (<1.0x109/L) 19 57.9 3.05 (1.24, 7.51) 4.00 (1.36, 11.80) Normal Lymphocyte Count 178 24.7 Macrocytosis (MCV>100fL) 71 14.1 0.34 (0.16, 0.74) 0.23 (0.09, 0.61) Normal MCV 117 32.5 Microcytosis (MCV<80fL) 11 63.6 2.91 (0.87, 9.77) 2.02 (0.50, 8.13) Current Antiretroviral Therapy 139 20.1 0.32 (0.17, 0.61) 0.43 (0.20, 0.95) No current Antiretroviral Therapy 61 44.3 Current Androgen Use 23 13.0 0.36 (0.10, 1.27) 0.20 (0.05, 0.84) No Current Androgen Use 171 28.7 EPO x Testosterone Interaction High EPO-High/nl Testosterone 46 41.3 2.50 (1.23, 5.11) 7.73 (2.92, 20.48) Low/nl EPO-Low Testosterone 24 37.5 2.39 (0.89, 6.39) 3.27 (1.01, 10.60) High EPO-Low Testosterone 11 27.3 0.33 (0.04, 2.50) 0.17 (0.012, 2.36) Low/nl EPO-High/nl Testosterone 115 20.9

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Age-Related Androgen Deficiency and Type 2 Diabetes

Journal of Pharmacy Practice ◽

10.1177/0897190010397719 ◽

2011 ◽

Vol 24 (3) ◽

pp. 316-322 ◽

Cited By ~ 2

Author(s):

Gina J. Ryan ◽

Lynetta J. Jobe

Keyword(s):

Type 2 Diabetes ◽

Hypogonadotropic Hypogonadism ◽

Treatment Options ◽

Mineral Density ◽

Testosterone Levels ◽

Know How ◽

Age Related ◽

Appropriate Therapy ◽

Low Testosterone

There is a higher prevalence of low testosterone levels in males with type 2 diabetes compared to those without. Additionally, there is evidence that low testosterone levels may predict the development of type 2 diabetes. Symptoms of hypogonadism include decreased libido, decreased bone mineral density (BMD), and decreased lean muscle mass. The majority of the published cases in men with diabetes were attributed to age-related idiopathic hypogonadotropic hypogonadism. This paper reviews the link between type 2 diabetes and age-related hypogonadism and the treatment options for hypogonadism. Pharmacists who provide care for males with diabetes should be aware of the increased incidence of hypogonadism, know how to screen for it, and be able to recommend appropriate therapy.

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Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-17-0055 ◽

2017 ◽

Vol 2017 ◽

Cited By ~ 3

Author(s):

B Cangiano ◽

C Cacciatore ◽

L Persani ◽

M Bonomi

Keyword(s):

Side Effects ◽

Replacement Therapy ◽

Late Onset ◽

Clomiphene Citrate ◽

Hypogonadotropic Hypogonadism ◽

Vitamin D Supplementation ◽

Testicular Volume ◽

Testosterone Replacement ◽

Testosterone Replacement Therapy ◽

List Type

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic–pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Learning points: Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment. In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone. In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions. Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.

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Andropause or Male Menopause? Rationale for Testosterone Replacement Therapy in Older Men with Low Testosterone Levels

Endocrine Practice ◽

10.4158/ep13217.ra ◽

2013 ◽

Vol 19 (5) ◽

pp. 847-852 ◽

Cited By ~ 8

Author(s):

Glenn Cunningham

Keyword(s):

Replacement Therapy ◽

Older Men ◽

Testosterone Replacement ◽

Testosterone Replacement Therapy ◽

Testosterone Levels ◽

Low Testosterone ◽

Male Menopause

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Testosterone, erectile dysfunction, and the heart

ESC CardioMed ◽

10.1093/med/9780198784906.003.0246 ◽

2018 ◽

pp. 1019-1024

Author(s):

Geoffrey Hackett

Keyword(s):

Erectile Dysfunction ◽

Cardiovascular Health ◽

Testosterone Replacement Therapy ◽

Testosterone Levels ◽

Low Sexual Desire ◽

Low Testosterone ◽

Low Levels

Testosterone therapy is a highly effective treatment for men with erectile dysfunction and low sexual desire with established testosterone deficiency. Several long-term studies have shown that low levels of testosterone are associated with increased all-cause mortality, cardiovascular events, onset of type 2 diabetes, and reduced quality of life. It would therefore seem logical that correcting inappropriately low testosterone levels might be beneficial for erections but also for cardiovascular health, yet it is not established medical practice to measure testosterone or treat confirmed low levels. A small number of published studies suggested risk associated with testosterone replacement therapy but several well conducted long-term longitudinal studies suggest consistent benefits especially when testosterone levels are restored to the normal range for a prolonged period.

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Polycythemia as a Complication of Testosterone Replacement Therapy in Nursing Home Men with Low Testosterone Levels

Journal of the American Geriatrics Society ◽

10.1111/j.1532-5415.1995.tb05534.x ◽

1995 ◽

Vol 43 (8) ◽

pp. 899-901 ◽

Cited By ~ 65

Author(s):

Paul J. Drinka ◽

Albert L. Jochen ◽

Mary Cuisinier ◽

Rosemary Bloom ◽

Inge Rudman ◽

...

Keyword(s):

Nursing Home ◽

Replacement Therapy ◽

Testosterone Replacement ◽

Testosterone Replacement Therapy ◽

Testosterone Levels ◽

Low Testosterone

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MON-273 Retrospective Analysis of Gonadotropin-Mediated Pubertal Induction in Male Patients with Congenital Hypogonadotropic Hypogonadism (CHH)

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1809 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Biagio Cangiano ◽

Giovanni Goggi ◽

Fabiana Guizzardi ◽

Valeria Vezzoli ◽

Paolo Duminuco ◽

...

Keyword(s):

Retrospective Analysis ◽

Multiple Regression ◽

Semen Analysis ◽

Final Height ◽

Pubertal Development ◽

Hypogonadotropic Hypogonadism ◽

Bone Age ◽

Testicular Development ◽

Testosterone Replacement Therapy ◽

Male Patients

Abstract CHH is a rare disease characterized by a failure to enter (complete forms) or to complete (partial forms) pubertal development. It has a strong genetic background and it needs a treatment to allow the puberty to complete. In male this goal could be achieved either by the classic testosterone replacement therapy or by the exogenous gonadotropins (Gn) administration which allows both the endogenous testosterone production and the testicular development. So far, only few studies have explored this latter therapeutic approach in inducing the CHH pubertal development and no internationally recognized protocols are available. Aim of this retrospective analysis is to (i) investigate clinical and biochemical predictors of testicular response to Gn-induced puberty in CHH; (ii) study the non-reproductive outcomes of this treatment (height, body proportions) and their determinants. A total of 19 CHH male patients, undergoing two years of Gn-mediated (FSH and hCG) puberty induction started between the ages of 14 and 23 years, were retrospectively evaluated. For each patient clinical history, physical examination, hormonal evaluation, and genetic analysis using Targeted Next Generation Sequencing for CHH genes was performed; 8 patients accepted to perform a semen analysis (SA) at the end of their treatment.Mann Whitney test and multiple regression analysis showed testicular volume after 24 months of Gn-mediated pubertal induction, to be significantly associated with: (i) the presence of cryptorchidism; (ii) the presence of a completely definable genetic cause for the disease; (iii) the presence of a complete CHH form. No significant association was found with the cumulative dose of hCG administered in 24 months. The statistical analyses regarding SA could not find the same associations. Multiple regression analyses investigating the eunuchoid habitus and a measure of the difference of subject’s final height from his target (deltaSDSth), showed a significant association with: (i) age at the beginning of the induction; (ii) the duration of growth during induction; (iii) and (for deltaSDSth) bone age before the induction. Duration of growth during induction resulted to be associated with previous testosterone priming and with partial CHH.In summary, our study confirms cryptorchidism and complete genetic forms of CHH as negative predictors of testicular response probably because they usually affect early phases of life with a complete GnRH deficiency. We also found that the eunuchoid habitus and deltaSDSth are associated not only with delayed treatment, but also with the duration of stature growth during the induction, apparently related to earlier androgenization.

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