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Submitted on March 30, 2005
Accepted on July 20, 2005
School of Women's and Infants' Health, University of Western Australia; Department of Clinical Immunology & Biochemical Genetics, Royal Perth Hospital and School of Surgery and Pathology, University of Western Australia; Department of Clinical Immunology & Biochemical Genetics, Royal Perth Hospital; Sydney Centre for Reproductive Health Research, F.P.A. Health and Department of Obstetrics and Gynaecology, University of Sydney, Australia; Prince Henry's Institute of Medical Research, Melbourne, Victoria, Australia
* To whom correspondence should be addressed. E-mail: mhickey{at}obsgyn.uwa.edu.au.
Context: Irregular bleeding affects many users of combined menopausal hormone therapy (HT) and commonly leads to invasive and expensive investigations to exclude underlying malignancy. In most cases no abnormality is found.
Objective: The main objective of this study was to explore the role of uterine natural killer (uNK) cells and their regulatory cytokine IL-15 in irregular bleeding in HT users.
Design: Prospective observational study conducted between 2002-04.
Setting: Tertiary referral menopause clinic at King Edward Memorial Hospital, Western Australia
Patients: One hundred and seventeen postmenopausal women taking continuous combined HT.
Interventions: Outpatient endometrial biopsies taking during and outside bleeding episodes.
Main Outcome Measures: The relationship between endometrial uNK cells (CD56+) and bleeding patterns. We also addressed the impact of HT exposure on uNK cell populations, the relationship between endometrial IL-15 expression and uNK cell populations and KIR genotype in subjects with irregular bleeding.
Results: Endometrial CD56+ uNK cells were significantly increased in biopsies obtained during bleeding episodes (P < 0.001) compared with HT users with no bleeding. The highest level of IL-15 expression was also seen in biopsies taken during bleeding. No clear relationship between KIR genotype and bleeding on HT was observed.
Conclusions: Little is known about the mechanisms underlying irregular bleeding in HT users. This is the first report of uNK cells and of their association with regulating cytokines in postmenopausal endometrium and demonstrates a possible mechanism by which HT may induce irregular bleeding.
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