Preventive MedicinePreventive Medicine Research Program
The program concentrates on the role of estradiol production in female adipose tissue depots with regard to cardiovascular and breast cancer prevention, and in register-based studies on the evaluation of cardiovascular risk associated with use of estradiol-containing postmenopausal hormone therapy.
Female breast. Human adipose tissue can produce estradiol (E2). Local reduction of estrogen production in the female breast adipose tissue may reduce breast cancer risk, while an increase may have the opposite effect. In postmenopausal women we have, unexpectedly, demonstrated lower E2 levels in the fat in cancer breasts than in controls. Another study in premenopausal women showed that E2 levels in breast fat appeared to be regulated by the menstrual cycle, but the regulation differed in cancerous breasts from that in control women.
Cardiovascular (CV) protection. We are investigating the E2 production in both subcutaneous and visceral fat aiming at finding out if this endogeneous estrogen could influence CV protection in the postmenopause. We report that the two prohormones dehydroepiandrosterone sulfate and estrone sulfate are hydrolyzed by steroid sulfatase liberating these steroids for endogenous E2 production in fat tissue. This possibility is of interest as CV protection by exogenous administration of conjugated estrogen-based hormone therapy (HT) in treatment trials in the USA has not proven possible.
Register-based studies. In our nationwide studies we have evaluated the risk of CV mortality among Finnish women who used E2-based HT as compared to the background population: HT was associated with reduced CV mortality, particularly in women initiating HT before age 60. HT discontinuation was accompanied by an increased risk for CV death, particularly in the first post-treatment year. These findings do not lend support to the current practice of yearly HT discontinuation to evaluate whether the woman could manage without HT. Further analyses will be carried out to shed light on this issue.
Veera Vihma, MD, PhD
Natalia Hetemäki, MD
Anne Ahmanheimo, Laboratory Nurse
Kirsti Räsänen, Laboratory Nurse
Paatela H, Wang F, Vihma V, Savolainen-Peltonen H, Mikkola TS, Turpeinen U, Hämäläinen E, Jauhiainen M, Tikkanen MJ. Steroid sulfatase activity in subcutaneous and visceral adipose tissue: a comparison between pre- and postmenopausal women. Eur J Endocrinol. 2016;174:167-75.
Vihma V, Wang F, Savolainen-Peltonen H, Turpeinen U, Hämäläinen E, Leidenius M, Mikkola TS, Tikkanen MJ. Quantitative determination of estrone by liquid chromatography-tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women. J Steroid Biochem Mol Biol. 2016;155:120-5.
Mikkola TS, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O. Vaginal estradiol use and the risk for cardiovascular mortality. Human Reproduction, 2016; 31:804-9.
Savolainen-Peltonen H, Tuomikoski P, Korhonen P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O, Mikkola TS. Cardiac Death Risk in Relation to the Age at Initiation or the Progestin Component of Hormone Therapies. Journal of Clin Endocrinol Metab, 2016;101:2794-801.
Fidarov AF, Vihma V, Bogautdinov RP, Morozkina SN, Shavva AG, Tikkanen MJ. Novel structural features increase the antioxidant effect of estrogen analogues on low density lipoprotein. J Steroid Biochem Mol Biol. 2015 Nov;154:142-9.
Mikkola TS, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab 2015;100:4588-94.
Folkhälsan Research Foundation
EVO Governmental Grants
Jane and Aatos Erkko Foundation
Päivikki and Sakari Sohlberg Foundation
Sigrid Jusélius Foundation
Academy of Finland
Hanna Savolainen-Peltonen, MD, PhD
Kirsi Pietiläinen, MD, PhD
Matti Jauhiainen, PhD
Esa Hämäläinen, MD, PhD
Ursula Turpeinen, PhD