Androgen associations with bone turnover across reproductive-endocrine disorders reveal endocrine influences beyond oestrogen

Jovanna Tsoutsouki; Mills Edouard G.; S. Pierret Aureliane C.; Agathoklis Efthymiadis; Kanyada Koysombat; Megan Young; Sandhi Nyunt; Yeung Arthur C.; Maria Phylactou; Ali Abbara; Dhillo* Waljit S.; Comninos* Alexander N.

doi:10.1530/obabs.08.OC3.6

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Bone Abstracts (2026) 8 OC3.6 | DOI: 10.1530/obabs.08.OC3.6

OP2026 Oral Communications Oral Communications 3: Research 2 (7 abstracts)

Androgen associations with bone turnover across reproductive-endocrine disorders reveal endocrine influences beyond oestrogen

Jovanna Tsoutsouki ^1,2 , Edouard G. Mills ^1,2,3 , Aureliane C. S. Pierret ¹ , Agathoklis Efthymiadis ¹ , Kanyada Koysombat ¹ , Megan Young ¹ , Sandhi Nyunt ¹ , Arthur C. Yeung ¹ , Maria Phylactou ¹ , Ali Abbara ¹ , Waljit S. Dhillo* ^1,2 & Alexander N. Comninos* ^1,2,3

Author affiliations

¹Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; ²Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom; ³Endocrine Bone Unit, Imperial College Healthcare NHS Trust, London, United Kingdom *Waljit Dhillo and Alexander Comninos are co-senior and co-corresponding authors

Background: Bone turnover disturbances in reproductive disorders are frequently attributed to altered oestrogen exposure. However, reproductive-endocrine conditions involve broader dysregulation across metabolic, adrenal, and hypothalamic axes. Whether bone turnover reflects shared or condition-specific endocrine regulation across these states remains unclear.

Methods: Using a comparative approach, fasting bone turnover markers (BTMs; P1NP, CTX) were measured in women aged 20-36 years not receiving hormonal therapy: healthy controls (n26), hypothalamic amenorrhea (HA; n29), congenital hypogonadotropic hypogonadism (CHH; n9), and polycystic ovary syndrome (PCOS; n56). Group differences were assessed using Kruskal-Wallis tests and within-group endocrine associations using Spearman correlations.

Results: Bone turnover was highest in CHH (median CTX 0.61 ng/mL; P1NP 86.7 ng/mL) compared with controls (CTX 0.38; P1NP 57.3), HA (CTX 0.39; P1NP 58.1), and PCOS (CTX 0.34; P1NP 53.1; all P ≤0.02 vs. CHH). Despite comparable oestradiol concentrations in CHH and HA, both resorption and formation markers were significantly elevated in CHH, implicating mechanisms beyond current sex steroid exposure. Across groups, androgens emerged as consistent positive correlates of bone turnover: CTX correlated with androstenedione and dihydrotestosterone in controls (r 0.44, P 0.04) and HA (r 0.46, P 0.03), and with DHEAS in PCOS (r 0.29, P 0.04). P1NP correlated with dihydrotestosterone and androstenedione in controls (r 0.45-0.53, P 0.03) and HA (r 0.46-0.49, P 0.03), testosterone in PCOS (r 0.36, P 0.01) and strongly with DHEAS in CHH (r 0.82, P 0.03). Condition-specific patterns were evident: in HA, P1NP associated with hypothalamic suppression indices (LH: r 0.51, P 0.01; oestradiol: r 0.53, P 0.008) and disruption across additional axes (IGF1: r 0.44, P 0.03; fT3: r 0.49, P 0.02). In PCOS, CTX correlated inversely with BMI (r 0.31, P 0.02), indicating adiposity-mediated suppression of bone resorption.

Conclusion: Androgens consistently correlate with bone turnover across reproductive-endocrine states, challenging purely oestrogen-centric models of female bone metabolism. Elevated bone turnover in CHH, despite profound oestrogen deficiency comparable to HA, highlights contributions of androgen and non-gonadal steroid pathways. In HA, bone formation associates with multi-axis endocrine disruption rather than isolated gonadal suppression, while in PCOS metabolic context modulates resorption. These findings identify androgens as underappreciated determinants of bone regulation and support condition-specific, phenotypic approaches to skeletal risk assessment beyond oestrogen alone.