Progestogen addition with low-dose levonorgestrel intrauterine system in menopausal hormone treatment gives less normal breast tissue proliferation than oral norethisterone acetate or medroxyprogesterone acetate.

Background The impact of hormones on the development of breast cancer is despite extensive studies, incompletely understood. Combined estrogen-progestogen treatment augments the risk for breast cancer beyond that of estrogen alone, according to numerous studies. The role of breast cell proliferation as a promoter in the development and growth of breast cancer is well recognized. Materials and methods Seventy-nine patients from three randomised trials were subject to a re-analysis of breast cell proliferation: (1) 22 women received continuous combined treatment with oral estradiol (E2) 2 mg/norethisterone acetate (NETA) 1 mg once daily for 3 months. (2) Thirty-seven women received 2 months of sequential treatment with oral conjugated equine estrogens (CEE) 0.625 mg daily combined with medroxyprogesterone acetate (MPA) 5 mg for 14/28 days of each cycle. (3) Twenty women received oral estradiol-valerate (E2V) 2 mg daily combined with levonorgestrel (LNG) intrauterine system (IUS), 20 µg/24 h for 2 months. Fine needle aspiration (FNA) (studies 1 and 3) and core needle biopsy (CNB) (study 2) were used for the assessment of breast cell proliferation. Results There were no baseline proliferation differences, but at the end of treatment there was a highly significant between-group difference for E2V/LNG IUS versus the other two groups (p = 0.0025). E2/NETA and CEE treatments gave a 4-7-old increase in proliferation during treatment (p = 0.04) and (p = 0.007), respectively, which was absent in the E2V/LNG group, showing a significant correlation with insulin-like growth factor binding protein-3 (IGFBP-3) serum levels. Conclusion E2V in combination with very low serum concentrations of LNG in the IUS gives no increase in proliferation in the normal breast.