Hormonal risk factors and androgen and glucocorticoid dysregulation in Sjogren's disease and non-Sjogren's sicca.

Abstract

The strong female sex bias in Sjögren's disease (SjD) remains poorly understood. We evaluated hormonal risk factors and steroidal hormones in a well-characterized cohort. Newly presenting patients investigated for SjD at a multidisciplinary clinic completed a hormonal risk factor questionnaire. One hundred eighty-four females with a diagnosis of SjD or non-SjD Sicca were included. Steroids were extracted from 88 consecutively recruited SjD and 59 Sicca serum samples and analysed via liquid chromatography tandem mass spectrometry. Sex steroid, glucocorticoid and mineralocorticoid data were compared with those from 165 healthy controls. A history of hirsutism was negatively associated with SjD even when corrected for smoking status, ethnicity, age and symptom duration (OR 0.14, 95% CI 0.04, 0.57; P = 0.006), whereas hysterectomy and ovary removal were positively associated, whether up to time of recruitment (hysterectomy OR 3.29, 95% CI 1.19, 9.11; P = 0.02) or to symptom onset (hysterectomy OR 5.8, 95% 1.52, 22.1; P = 0.01). Participants reporting hirsutism had higher androstenedione levels (2.51 vs 1.80 nmol/l; P = 0.03) and in pre-menopause, androstenedione and testosterone were higher in non-SjD sicca than both SjD and healthy controls. Within the whole cohort, androstenedione levels were inversely correlated with minor salivary gland focus score (r = -0.44; P = 0.03). Lower glucocorticoids were seen in both SjD and Sicca compared with healthy controls and negatively correlated with symptoms. Participants with SjD were less likely to report hirsutism and had lower androstenedione and testosterone pre-menopause when compared with non-SjD sicca. The role of androgens in modulating salivary gland inflammation should be further investigated.