A Novel Risk Stratification for Infertile Men

Michael Scally MD

Doctor of Medicine
10+ Year Member
Ventimiglia E, Ippolito S, Capogrosso P, et al. Primary, secondary and compensated hypogonadism: a novel risk stratification for infertile men. Andrology 2017;5(3):505-10. http://onlinelibrary.wiley.com/doi/10.1111/andr.12335/abstract

Recently, the cohort of men from the European Male Ageing Study has been stratified into different categories distinguishing primary, secondary and compensated hypogonadism. A similar classification has not yet been applied to the infertile population.

We performed a cross-sectional study enrolling 786 consecutive Caucasian-European infertile men segregated into
· eugonadal [normal serum total testosterone (>/=3.03 ng/mL) and normal luteinizing hormone (</=9.4 mU/mL)],
· secondary (low total testosterone, low/normal luteinizing hormone),
· primary (low total testosterone, elevated luteinizing hormone) and
· compensated hypogonadism (normal total testosterone; elevated luteinizing hormone).

In this cross-sectional study, logistic regression models tested the association between semen parameters, clinical characteristics and the defined gonadal status.

Eugonadism, secondary, primary and compensated hypogonadism were found in 80, 15, 2, and 3% of men respectively.

Secondary hypogonadal men were at highest risk for obesity [OR (95% CI): 3.48 (1.98-6.01)].

Primary hypogonadal men were those at highest risk for azoospermia [24.54 (6.39-161.39)] and testicular volume <15 mL [12.80 (3.40-83.26)].

Compensated had a similar profile to primary hypogonadal men, while their risk of azoospermia [5.31 (2.25-13.10)] and small testicular volume [8.04 (3.17-24.66)] was lower. The risk of small testicular volume [1.52 (1.01-2.33)] and azoospermia [1.76 (1.09-2.82)] was increased, although in a milder fashion, in secondary hypogonadal men as well.

Overall, primary and compensated hypogonadism depicted the worst clinical picture in terms of impaired fertility. Although not specifically designed for infertile men, European Male Ageing Study categories might serve as a clinical stratification tool even in this setting.


 
Elevated Luteinising Hormone despite Normal Testosterone Levels in older Men – Natural History, Risk Factors, and Clinical Features

Objective - Elevated LH with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH>9.4 U/L) in ageing men with normal T (T≥10.5 nmol/L).

Design, Patients and Measurements - We conducted a 4.3 year prospective observational study of 3,369 community-dwelling European men aged 40-79 years.

Participants were classified as:
incident (i) HLH (n=101, 5.2%);
persistent (p) HLH (n=128, 6.6%); r
everted (r) HLH (n=46, 2.4%); or
persistent normal LH (pNLH, n=1667, 85.8%).

Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models.

Results - Age >70 years (OR=4.12[2.07–8.20]), diabetes (OR=2.86[1.42–5.77]), chronic pain (OR=2.53[1.34–4.77]), pre-degree education (OR=1.79[1.01–3.20]) and low physical activity (PASE≤78, OR=2.37[1.24–4.50]) predicted development of HLH. Younger age (40-49 years, OR=8.14[1.35-49.13]) and non-smoking (OR=5.39[1.48–19.65]) predicted recovery from HLH.

Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, co-morbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men.

Men with HLH developed primary hypogonadism more frequently (OR=15.97[5.85–43.60]) than NLH men.

Men with rHLH experienced a small rise in BMI.

Conclusions - Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.

The EMAS Group. Elevated Luteinising Hormone despite Normal Testosterone Levels in older Men – Natural History, Risk Factors, and Clinical Features. Clin Endocrinol. http://onlinelibrary.wiley.com/doi/10.1111/cen.13524/abstract
 
Back
Top