Published 8th August 2025

Hypogonadism is a common but often under-recognized complication among men living with type 2 diabetes mellitus (T2DM) in Asia, particularly in Malaysia. This condition can be classified into two distinct forms:

• Hypogonadotropic hypogonadism (Hypo-H) – characterized by low or inappropriately normal luteinizing hormone (LH) levels, often linked to insulin resistance and visceral adiposity.
• Hypergonadotropic hypogonadism (Hyper-H) – marked by elevated LH levels, generally associated with primary testicular dysfunction.

While Hypo-H is well-studied in metabolic disease, less is known about Hyper-H in diabetic men, particularly in Malaysia, where obesity and poorly controlled diabetes are highly prevalent.

Study Overview

Researchers screened 360 Malaysian men with T2DM between 2019–2020. Hypogonadism was diagnosed using stringent criteria:

• Total testosterone <12 nmol/L
• Free testosterone <0.255 nmol/L (calculated)
• Aging Male Symptoms (AMS) score ≥27

Patients were classified as Hypo-H or Hyper-H based on LH levels (>8.6 mIU/mL for Hyper-H). Eugonadal men served as controls.

Key Findings

• Prevalence: Of 63 hypogonadal men, 55.6% had Hypo-H and 44.4% had Hyper-H.
• Age Trends: Hyper-H prevalence increased steadily with age (mean age 61.7 years vs. 56.4 in eugonadal men). Hypo-H was more common in slightly younger men (mean age 58.7 years).
• Anthropometric and Metabolic Links:
  • Hypo-H patients had higher BMI, greater abdominal adiposity, and elevated triglycerides, alongside lower HDL-C levels and higher insulin resistance (TyG index) compared to eugonadal men.
  • For Hyper-H, age was the only significant differentiator from eugonadal men 1.
• Cardiovascular Connection: Men with coronary artery disease (CAD) had twice the odds of hypogonadism. Low HDL-C significantly reduced the risk of hypogonadism.

Pathophysiological Insights

Hypo-H in T2DM is closely tied to obesity and metabolic syndrome, creating a vicious cycle:

1. Visceral adiposity → insulin resistance → pro-inflammatory cytokines
2. Cytokines lower SHBG and impair Leydig cell testosterone production
3. Low testosterone further promotes visceral fat accumulation.

Hyper-H, on the other hand, appears more age-driven, possibly due to Leydig cell dysfunction and reduced LH pulse amplitude in older men. Environmental factors such as endocrine-disrupting chemicals (EDCs) — notably bisphenol A and triclosan detected in Klang Valley’s water supply — may play a role by directly impairing testicular function.

Why This Matters

For healthcare providers specializing in weight and metabolic health, these findings highlight two crucial clinical distinctions:

1. Hypo-H is a metabolic problem — strongly linked to obesity, insulin resistance, and dyslipidemia.
   • Interventions: Weight loss, visceral fat reduction, and insulin-sensitizing strategies are key.
   • Potential tools: Lifestyle modification, SGLT-2 inhibitors, GLP-1 receptor agonists, and dual GIP-GLP-1 agonists — all shown in small studies to improve testosterone levels and sexual function.
2. Hyper-H is more age-related, potentially with environmental triggers.
   • Management may require testosterone replacement therapy or addressing environmental toxicant exposure, rather than purely metabolic interventions.

Clinical Takeaways

• Recognize hypogonadism as a common comorbidity in Malaysian men with T2DM, especially those with high BMI, low HDL-C, and CAD risk.
• Differentiate between Hypo-H and Hyper-H — the underlying drivers, and thus treatment strategies, differ markedly.
• In Hypo-H, targeting weight loss and visceral fat reduction may restore hormonal balance.
• Environmental health awareness — consider the possible influence of EDCs in local populations on endocrine health.

Conclusion

This study underscores that not all hypogonadism in diabetic men is the same. For weight management specialists, understanding these distinct patterns is vital for tailoring interventions, particularly to rule out hypogonadism in Asian men.

Hypo-H is a metabolic consequence, treat the weight, improve the hormones.
Hyper-H is more age and potentially toxin-driven may need a different therapeutic pathway.

Given that hyper-H prevalence in this Malaysian cohort was double that reported elsewhere, further research is urgently needed to explore environmental and lifestyle contributors.

SOURCE / READ THE FULL PAPER  https://doi.org/10.1111/jdi.70127

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