Does low testosterone in women cause insulin resistance?

Testosterone's role in female metabolic health is complex and sexually dimorphic. While testosterone acts as a significant anabolic agent in skeletal muscle, its broader impact on systemic insulin sensitivity in women differs substantially from its role in men.

Clinical evidence and anabolic signaling

Testosterone is a critical regulator of muscle protein synthesis (MPS) and muscle mass in women.

• Anabolic Signaling: Evidence from hypogonadal and post-hysterectomy women confirms that low testosterone impairs the Akt-mTOR signaling cascade. Specifically, testosterone deficiency reduces the phosphorylation of mTORC1 and its downstream targets, p70S6K1 and 4E-BP1, which are essential for initiating mRNA translation.
• Muscle Maintenance: Testosterone supports the proliferation of satellite cells and increases myogenin expression. Clinical trials demonstrate that testosterone replacement in women with low levels can significantly increase the cross-sectional area of trunk muscles (e.g., psoas and paraspinal muscles) and improve lean body mass.

Glucose disposal and insulin resistance

The relationship between testosterone and glucose metabolism in women is paradoxical compared to the muscle-building effects.

• Glucose Disposal Mechanisms: It is mechanistically plausible that low testosterone could impair muscle glucose disposal. In human skeletal muscle cells, testosterone activates AKT, ERK, and mTOR while inhibiting GSK3β, which facilitates the translocation of GLUT4 to the cell membrane. Lower testosterone levels theoretically reduce this signaling and the overall "metabolic sink" (muscle mass) available for glucose clearance.
• Insulin Resistance: Despite the muscle-specific effects, clinical evidence does not support the idea that low testosterone contributes to systemic insulin resistance in women. In fact, the opposite is true: hyperandrogenism (high testosterone) is strongly associated with insulin resistance and metabolic dysfunction in women, most notably in conditions like Polycystic Ovary Syndrome (PCOS). Large cohort studies, such as the KORA study, indicate that higher testosterone levels in women correlate with worsened HOMA-IR and BMI.

Bottom line

While low testosterone in women reduces muscle anabolic signaling and may theoretically lower muscle-specific glucose uptake pathways, it is not a recognized driver of systemic insulin resistance. In clinical practice, it is high, rather than low, testosterone that serves as the androgenic risk factor for metabolic disease in women.