STARSHIP: Study of Telomeres And Role of Sex Hormones In Pulmonary fibrosis
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Background
Fibrotic interstitial lung disease (F-ILD) has high mortality. Evidence suggests short telomere causality and sex hormone interactions. STARSHIP aimed to assess feasibility for future F-ILD sex hormone trials.
Methods
Leukocyte telomere length (LTL), complete blood count, sex hormone (testosterone and oestrogen), sex hormone binding globulin (SHBG) and albumin concentrations were determined in 102 F-ILD outpatients (age 49-89, male N=80 [78%]) and age/sex-matched controls (ASMCs). Patients undertook routine pulmonary function tests, 93 (91%) participated in bespoke telephone interviews. Survival was assessed at median 33 (28-39) months.
Results
77/79 (97.4%) male patients had haemoglobin and haematocrit below the upper reference limit. Mean LTL was shorter for patients than ASMCs (4.57kb [95%CI:4.46-4.69] vs 4.78kb [95%CI:4.67-4.89]; p<0.006). SHBG concentrations were higher for patients. Mean bioavailable testosterone was lower for N=80 male patients than ASMCs (4.95nmol/L [95%CI:4.50-5.41] vs 6.40nmol/L [95%CI:5.82-6.98]; p<0.0001). Post-menopausal oestrogen concentrations were low for female patients and controls. Mean free androgen index (FAI) was low for female patients but not ASMCs (mean 0.51 [95%CI:0.35-0.67] vs 1.23 [95%CI:0.77-1.69]; p=0.0036, N=22). Age/BMI-adjusted bioavailable testosterone concentration in male patients correlated with both DLCO% ( β =3.31, p=2.4×10 -4 ) and FVC% ( β =2.76, p=0.0030). FVC% associated with FAI in females ( β =34.3, p=0.0029). In all-confounder-adjusted Cox analysis, low free testosterone associated with mortality (HR=2.66, p=0.023, N=77) in male patients. Lower FAI (adjusted for age/lung function) suggested similar effects but more studies needed for females (HR=3.59, p=0.22, N=18).
Conclusions
ILD patients have low sex hormones concentration(s), which associated with reduced lung function and survival. Sex hormone supplementation studies are needed.
Key messages
Using population data, we have previously shown a three-way association between short telomeres, low sex hormones and higher pulmonary fibrosis (PF) prevalence. However, no clinical data on sex hormone concentrations for PF patients and links with lung function and survival have been reported. Here we show, in a prospective clinical study, that male and female patients presenting to the interstitial lung disease clinic with PF have lower sex hormone concentrations than age- and sex-matched controls, which is associated with worse lung function and reduced survival. The findings highlight the need to explore potential benefits of hormone supplementation in PF.
