Association Between Sex Hormones and Lipid Profiles Among Adult Tuberculosis Patients in Northwest Ethiopia: A Comparative Cross‐Sectional Study

Abstract

BACKGROUND: Tuberculosis (TB) remains a major global health burden, particularly in low- and middle-income countries. Persistent TB-related inflammation has been implicated in significant endocrine and metabolic dysregulation. While previous studies have documented alterations in sex hormones or lipid profiles independently, the potential interplay between these biological systems has not been systematically investigated in patients with active TB. Moreover, comprehensive evidence from sub-Saharan Africa, including Ethiopia, where the burden of TB is substantial, remains limited. Elucidating the hormone-lipid interrelationship may provide important insights into the pathophysiological mechanisms underlying TB-associated metabolic disturbances. Therefore, this study aimed to comprehensively evaluate alterations in sex hormones and lipid profiles and to examine their interrelationships among adult TB patients in Gondar town, Northwest Ethiopia. METHODS: A comparative cross-sectional study was conducted among 150 HIV-negative, TB-positive patients (both newly diagnosed and on anti-TB treatment) and 150 age-matched TB-negative adults recruited from five selected health institutions in Gondar Town. Sociodemographic, clinical and behavioural data were collected using structured interviews. Fasting serum samples were analysed for lipid profiles, sex hormones and cortisol using a Beckman Coulter Clinical Chemistry analyser. Group comparisons were performed using t-tests and the Mann-Whitney U test and correlations were assessed using Pearson and Spearman's rank coefficients. Statistical significance was set at p < 0.05. RESULTS: Male TB-positive patients had significantly lower testosterone (mean difference: -2.6, 95% CI: -3.1 to -2.1), while oestradiol (+15.1, 95% CI: 9.5-20.7), LH (+5.8, 95% CI: 3.2-8.3) and FSH (+6.6, 95% CI: 4.1-9.0) levels were significantly higher compared with tuberculosis-negative individuals (p < 0.001). Female TB-positive patients showed markedly reduced testosterone and progesterone levels (p < 0.001, r = 0.7 and 0.4, respectively). Among females, testosterone levels were lower in underweight than normal-weight individuals (p = 0.006; overall p = 0.008), with no other hormone variations by BMI in either sex. Regarding lipid profiles, TB-positive patients exhibited significantly lower total cholesterol (mean difference: -40.5 mg/dL, 95% CI: -50.1 to -30.9, p < 0.001), while LDL (-15.7 mg/dL, 95% CI: -25.6 to 5.8), HDL (2.5 mg/dL, 95% CI: -3.5 to 8.4) and triglycerides (-0.5 mg/dL, 95% CI: -3.1 to 2.2) showed no significant differences. Among male participants, cholesterol was positively correlated with testosterone (r = 0.658, p < 0.001) and negatively correlated with oestradiol (r = -0.314, p = 0.002), FSH (r = -0.31, p < 0.001), LH (r = -0.223, p = 0.004) and cortisol (r = -0.424, p < 0.001). Among female participants, cholesterol was positively correlated with testosterone (r = 0.299, p < 0.001). CONCLUSIONS: TB was associated with substantial disruptions in sex hormone balance and lipid metabolism. Male and female TB patients showed distinct alterations in gonadal hormones, alongside BMI-related variations in testosterone among females. Reduced total cholesterol was consistently observed in TB-positive patients, including both newly diagnosed and treated cases. In addition, TB patients on treatment had significantly lower triglyceride levels compared with both newly diagnosed TB patients and TB-negative controls, while underweight individuals exhibited lower triglyceride levels compared with overweight individuals. These findings suggest an association between tuberculosis, endocrine disruption and altered lipid metabolism, with potential implications for disease severity, nutritional status and recovery. However, given the cross-sectional design of this study, causal relationships cannot be established. Integrating hormonal and lipid assessments into TB care may improve patient monitoring and support clinical management.