Different Estrogen Sensitivity of Urogenital Tissue from Women with and Without Stress Urinary Incontinence

Aims: Oral hormone replacement therapy (HRT) based on estradiol-17beta (E2), E2 esters or conjugated equine estrogens gives rise to huge amounts of circulating estrone (E1) as a result of the first liver pass. E1 is an estrogen (ER) receptor agonist but has also been reported to act as a partial E2 antagonist in vitro. Our aim was to investigate the influence of circulating estrogens on estrogen sensitivity of urogenital tissue collagen turnover in patients with stress urinary incontinence (SUI) and in urologically healthy women, with and without HRT, in view of possible effects of E1 as a partial E2 antagonist.

Methods: Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and E1 and E2 were analyzed in serum from 54 patients with SUI and 29 urologically healthy women.

Results: In the total control group only a significant positive correlation was found between E2 and T-PICP. Lowering the upper serum E1 limit resulted in significant positive correlations also between E2 and T-PIIINP and finally also between E2 and T-ICTP. This pattern was found also in subgroups of post- and premenopausal controls. No association between serum E2 and collagen turnover markers and no effects of lowering the upper serum E1 limit was found in the total and postmenopausal SUI patients, while the correlation pattern in premenopausal SUI patients showed some resemblance to that in the controls.

Conclusion: At physiological E1 levels E2 increases collagen turnover in urogenital tissue in urologically healthy women but not in women with SUI in general; however, there was a certain effect of E2 in premenopausal but not in postmenopausal SUI patients. Urogenital tissue in SUI patients and in urologically healthy women may differ in estrogen sensitivty and in SUI patients this difference may be related to menopause. Circulating E1, which is present in huge amounts during oral HRT, may act as an estrogen receptor agonist as well as a partial E2 antagonist also in humans in vivo.