Is androgen production in association with immune system activation potential evidence for existence of a functional adrenal/ovarian autoimmune system in women?

Abstract

BackgroundLow functional ovarian reserve (FOR) is at all ages associated with low testosterone (T) levels. Causes are, however, unknown. We, therefore, investigate whether androgens with low FOR are associated with non-specific immune system activation.Methods322 infertile women with low and normal FOR (controls) were assessed with a broadly based immune profile, which in previous studies has proven effective in differentiating infertile patients with and without immune system activation. Patients were either immune-positive (greater than or equal to one positive tested parameter) or immune negative (no positive test). 135 suffered from prematurely diminished FOR (POA/OPOI; < age 38), 155 from physiologic diminished FOR due to age (DOR; > age 40), and 32 were controls (< age 38 with normal age-specific FOR). Prevalence of immune-positive vs. negative was assessed in all 3 patient groups.ResultsWomen with immune abnormalities, overall, demonstrated higher total T (TT, P = 0.004) and free T (FT, P < 0.001) levels than those without. The three clinical and two immunologic-defined patient groups demonstrated significant statistical interaction in mean TT (P = 0.008), with mean TT and FT in women with positive immune findings being significantly higher in control than in POA/OPOI and physiologic DOR patients (all 4 differences P < 0.001). No such differences between the three groups were seen in women without immune abnormalities.ConclusionsIn this study we used a definition of immune-positivity, which favors sensitivity over specificity, resulting in significant numbers of false-positives but likely only few false-negatives. The study allows suggesting the possibility of an immune system-derived androgen-production factor (APF), which maintains normal androgen levels but is deficient in women with low FOR and immune system inactivity. Existence of such an APF would suggest the presence of a still unknown functional adrenal autoimmune system.

High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

“…CCL2 and other proinflammatory cytokines are negatively associated with testosterone serum levels in obese men . Recently, several studies have indicated that testosterone is a potent immunosuppressor that may negatively influence the recruitment of macrophages to tumor tissue at higher serum concentrations . This is the first study to show a gender‐specific effect of CCL2 and CX3CL1 mRNA expression on the disease‐specific survival of STS patients.…”

Some aspects of interactivity between endocrine and immune systems required for successful reproduction

“…Fully expecting a high degree of false-positivity, any positive finding in the panel is clinically considered to represent immune system activation, and only complete absence of any positive findings is clinically considered a quiescent immune system [11]. …”

“…Yet, somewhat counter intuitively, we also discovered that they demonstrated no evidence whatsoever of immune system activation as we initially had hypothesized; yet, young, healthy control patients with normal androgen levels, to some degree did demonstrate evidence of immune system activation [11]. …”

Genetic associations with diminished ovarian reserve: a systematic review of the literature

“…Several studies have suggested an autoimmune association with DOR [48,49,4,50]. Unfortunately, no standard exists for defining those with autoimmune features.…”

“…Unfortunately, no standard exists for defining those with autoimmune features. Most studies have used only one positive autoimmune antibody to classify a patient as having abnormal autoimmune function [48,4,49].…”