Piltonen Terhi

Reproductive and metabolic health in women with polycystic ovary syndrome (PCOS) – a translational research approach to the most common endocrinological disorder of women

 

 Research unit: PEDEGO

 

Group leader

Terhi Piltonen MD, PhD  (ORCHID ID: https://orcid.org/0000-0002-9921-7300) is a professor at the Department of Obstetrics and Gynecology in Oulu University Hospital, and in University of Oulu, FINLAND. She also practices at the Reproductive Endocrinology and IVF Unit in the Oulu University Hospital. She has been principal investigator since 2013 after returning from her post-doctoral training period in UCSF, CA, US (2010-2012). Since then her team has focused on the lifelong health in women with polycystic ovary syndrome (PCOS); hyperandrogenism, mental and metabolic health issues. Lately, her research has also focused on early onset of PCOS.  Dr. Piltonen has also interest on endometrial function and hormonal contraceptives and she has carried out several clinical trials focusing on this area. Currently, she also runs a large clinical data collection in the Northern Finland birth cohort to screen gynecological symptoms and diseases that translate into adverse metabolic or psychological outcomes and decreased quality of life in women. Dr. Piltonen serves as associate editor in Fertility and Sterility and as a board member in the Androgen Excess and PCOS Society and the Finnish Endocrine Society. Dr. Piltonen has published extensively in the field of PCOS, contraception and endometrial functions with over 60 peer reviewed publications. 

 

Professor Terhi Piltonen

 

What do we do

Polycystic ovary syndrome (PCOS) affects 10-18% of fertile aged women and it is characterized by hyperandrogenism and chronic oligo-anovulation. Up to 50-70% of women with PCOS are obese and the women present with metabolic derangements. Interestingly, some women will not present the clinical, diagnostic features (oligo-anovulation, hyperandrogenism) until gaining weight, thus the syndrome is tightly linked with obesity. Due to anovulation, some women have difficulties to achieve spontaneous pregnancy and most of the diagnosis are set in the infertility clinics. However, especially the obese women with PCOS would benefit life style counselling, glucose metabolism testing and antiandrogenic treatments for excessive body hair even outside fertility context. Considering that the syndrome has been shown to associate with several co-morbidities (type 2 diabetes, hypertension, dyslipidemia, stroke, pregnancy complications, and endometrial cancer) and psychosocial burden (anxiety, depression, eating disorders), correct, timely diagnosis, early support and common guidelines are warranted.

Anti-müllerian hormone (AMH) – the culprit for PCOS transgenerational transmission?

The heritability of the syndrome has been estimated to be as strong as 70 % but genetic factors explain less than 10 % of the cases.  To date it is thought that the syndrome stems from androgen exposure during fetal life. Anti-Müllerian hormone (AMH) is expressed from growing antral follicles and its levels correlate well with antral follicle counts, thus reflecting the size of the follicle reserve. Women with PCOS have 2-3 times higher levels of AMH compared to other women. In mice high AMH can increase gonadotrophin releasing hormone (GnRH) pulsatility in brain, leading to increased luteinizing hormone (LH) pulsatility and hormonal imbalance, features often detected in women with PCOS also. In addition, a recent publication revealed that high AMH exposure in mice during pregnancy induced a PCOS-like phenotype in the female offspring later in life. We have shown that women with PCOS have higher AMH-levels even at the end of their pregnancies and we intend to study how high AMH levels affect the placenta and fetus, and whether women with PCOS, who have high AMH levels, have an increased risk for pregnancy complications. Starting in 2021 a new PEPPI study will shed light on the heritability and pregnancy risks in women with PCOS.

Function of the endometrium in women with PCOS

The inner epithelial lining of the uterus, called endometrium, is a hormone responsive tissue which grows and sheds in response to fluctuating levels of ovarian-derived steroid hormones. Endometrium lining consists of simple columnar epithelium that is in tight connection with underlying stromal cells, enabling complex interaction between these two cell compartments. Resident and migrating immune cells are also important for the function of the endometrium. Interestingly, perivascular stem cell populations have also been identified in human endometrium possibly contributing in the monthly renewal of the endometrial lining. Women with PCOS have been show to present with an altered endometrial function related to steroid hormone action and/or metabolism possibly contributing to infertility/subfertility as well as to endometrial cancer risk in women with PCOS.

Effects of hormonal contraception on female health

Hormonal contraceptives, commonly used in treating women with PCOS and endometriosis but also many other gynaecological conditions, have crucial role in female hormone therapy. Besides well documented benefits, recent studies have indicated impairment in metabolic parameters (glucose and lipid metabolism and low grade inflammation) in women with no previous risk factors.  Whether some estrogen/progestin combinations are metabolically more beneficial and should thus be recommended to women with pre-existing unfavourable metabolic profile is not well established.

Epidemiological studies

The epidemiological studies mostly base on both 1966 and 1986 Northern Finland Birth Cohorts (http://www.oulu.fi/nfbc/node/44315). The main interests of the epidemiological side are PCOS and endometriosis and their impact on health and quality of life of the affected women. In 2020 the Piltonen lab started conducting a data collection for all women who are part of the Northern Finland Birth Cohort 1986. The aim of the collection is to improve health of women in their reproductive years and to study the incidence of health conditions, that affect Finnish women, e.g. PCOS, endometriosis, diastasis recti and ovarian aging. The collection is conducted in collaboration with Roche. More info on the study can be found at: http://nfbc1986-naiset.fi/.

Main focuses of the research team are:

  • To investigate the role of steroid hormones (hyperandrogenism or hypoestrogenism) on long-term metabolic and reproductive health in women, especially in women with PCOS.
  • Unravel the role of AMH in PCOS pathogenesis, especially the effects of AMH levels during pregnancy
  • To reveal mechanisms/pathways responsible for the altered endometrial function of women with PCOS
  • To assess the inflammatory and metabolic effects of hormonal contraceptives
  • To elucidate the role of inflammation, hypoxia and metabolism-related factors in endometrial regeneration and health - outcomes related to implantation and endometrial cancer
  • To assess the role of gynecological hormone-related disorders (PCOS and endometriosis) on mental distress, quality of life, life style factors and co-morbidity
  • To develop means and tools to increase awareness of female health and develop treatment guidelines

Materials and methods and facilities

The team has several ongoing clinical trials related to contraceptive use, endometrial function and metabolic health in women with PCOS. The molecular biology laboratory, cell culture facilities and the endometrial tissue bank are situated in the Clinical Research Center at the Faculty of Medicine (Kieppi building) whereas all patient visits take place in the Reproduction Unit at the Oulu University Hospital (OYS).

 

     

Wendy-team in Helsinki

 

Our team

Postdoctoral researchers

  • Riikka Arffman, PhD, Research Manager
  • Meri-Maija Ollila, MD, PhD

    Doctoral students

    • Marika Kangasniemi, MD
    • Salla Karjula, MD
    • Masuma Khatun, MSc
    • Emilia Koivuaho, BM
    • Elina Komsi, MSc, BM
    • Linda Kujanpää, MD
    • Henna-Riikka Rossi, MD
    • Seungbaek Lee, MSc
    • Lena Luyckx, MSc
    • Yiqun Tang, MD
    • Natalia Pujol Gualdo, MSc
    • Julius Nurmenniemi, BM
    • Mona-Marika Nurkkala, MD
    • Fia Sundelin, MD
    • Saara Vuontisjärvi, MD
    • Henri Lähdesmäki, MD

    Other staff

    • Elisa Korhonen, MSc, Statistician
    • Maarit Haarala, Laboratory technician

    Women's Health Study (WENDY) staff

    Oulu:

    • Susanna Savukoski, Research doctor
    • Jenni Kinnunen, Research doctor
    • Lotta Vuokila, Coordinating research nurse
    • Elina Huikari, Research nurse
    • Tuija Anttonen, Research nurse

    Helsinki:

    • Kaisu Luiro-Helve, MD, PhD, Research doctor
    • Maria Rajecki, MD, PhD, Research doctor
    • Birgit Björkroth, Research nurse
    • Maaret Ahola, Research nurse

     

     

    Where are we headed

    Improve long-term health and wellbeing of women with PCOS and increase PCOS awareness

     

    Our main collaborators

    ReproEndo-Team

    • Laure Morin-Papunen, Adjunct Professor, Department of Obstetrics and Gynecology, University of Oulu
    • Juha Tapanainen, Professor, Department of Obstetrics and Gynecology, University of Helsinki
    • Hannu Martikainen, Professor, Department of Obstetrics and Gynecology, University of Oulu
    • Maarit Niinimäki, MD, PhD, Department of Obstetrics and Gynecology, University of Oulu

    The Nordic PCOS Network

    • Marianne Anderssen, Professor, Odense University Hospital, Denmark
    • Dorte Glintborg, Associate Professor, Odense University Hospital, Denmark
    • Francisco Gomez Real, University of Bergen, Norway
    • Helle Karro, MD, PhD, University of Tartu, Estonia
    • Angelica Linden-Hirschberg Professor, Karolinska Institute, Sweden
    • Pernille Ravn, MD, PhD, Odense University Hospital, Denmark
    • Inger Sundström-Poromaa, Professor, University of Uppsala, Sweden
    • Elisabet Stener-Victorin, Associate Professor, Karolinska Institute, Sweden
    • Eszter Vanky, Professor, University of Trondheim, Norway

    PCOS-FINnetwork

    • Laure Morin-Papunen, MD, PhD, Adjunct Professor, Department of Obstetrics and Gynecology, University of Oulu
    • Juha S. Tapanainen, MD, PhD, Professor, Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital
    • Päivi Polo-Kantola, MD, PhD, Professor, Department of Obstetrics and Gynaecology, Turku University Hospital and University of Turku
    • Varpu Jokimaa, MD, PhD, Department of Obstetrics and Gynaecology, Turku University Hospital and University of Turku, Turku, Finland
    • Paula Kuivasaari-Pirinen, MD, PhD, Department of Obstetrics and Gynaecology, Kuopio University Hospital and University of Kuopio
    • Pia Das, MD, PhD, Department of Obstetrics and Gynecology, Tampere University Hospital and University of Tampere

    PCOS-Awareness Alliance

    • Helena Teede, Professor, School of Public Health and Preventive Medicine, Monash University, Australia
    • Robert Norman, Professor, University of Adelaide, Australia
    • Steven Franks, Professor, Imperial College, London
    • Anuja Dokras, Professor, University of Pennsylvania, USA
    • Joop Laven, Professor, Erasmus MC, University of Rotterdam, Netherlands
    • Kathleen Hoeger, Rochester University, USA

    Center for Life Course Health Research (ELITE), University of Oulu

    • Marjo-Riitta Järvelin, MD, PhD, Professor
    • Sylvain Sebert, PhD, Adjuct Professor
    • Leena Ala-Mursula, MD, PhD, Professor
    • Sirkka-Liisa Keinänen-Kiukaanniemi, MD, PhD, Professor
    • Johannes Kettunen, PhD, Professor
    • Jouko Miettunen, PhD, Professor
    • Juha Auvinen, MD, PhD

    Other collaborators

    • Andres Salumets, PhD, Professor, Professor of Reproductive Medicine, Senior Research Fellow in Genetics, Department of Obstetrics and Gynecology, University of Tartu, Estonia
    • Paolo Giacobini, PhD, French National Institute of Health and Medical Research (INSERM, tenured position), Jean-Pierre Aubert Research Center, Lille, France   
    • Joris Vriens, PhD, Associate Professor, Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeranation, KU Leuven, Leuven, Belgium
    • Peppi Karppinen, MD, PhD, Professor, Dean, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland
    • Linda C. Giudice, MD, PhD, Professor and Chair Department of Obstetrics, Gynecology & Reproductive Sciences, UCSF, San Francisco, California, USA
    • Kaarel Krjutškov, PhD, Head of Genomic Service Laboratory; Senior Researcher, Competence Center on Health Technologies, Estonia
    • Minna Ruddock, PhD, Associate Professor, Research Director in the Northern Finland Birth Cohort (NFBC)
    • Oskari Heikinheimo, Professor, Department of Obstetrics and Gynecology, University of Helsinki
    • Leif Andersson, Emeritus Professor, Department of Pathology, University of Helsinki
    • Ralf Butzow, Professor, Department of Pathology, University of Helsinki
    • Ulla Puistola, Professor, Department of Obstetrics and Gynecology, University of Oulu
    • Outi Uimari, MD, PhD, Department of Obstetrics and Gynecology, University of Oulu
    • Heikki Huikuri, Professor, Department of Internal Medicine /Cardiology, University of Oulu
    • Tuula Salo, Professor, Department of Dentistry, Oral pathology, University of Oulu
    • Petri Lehenkari, Professor, Department of Molecular Biology and Anatomy, University of Oulu
    • Annikki Liakka, MD, PhD, Department of Pathology, University of Oulu
    • Mikko Hallman, Professor (Emeritus), Department of Paediatrics, University of Oulu
    • Mika Rämet, Professor, Department of Paediatrics, University of Oulu
    • Marja Vääräsmäki, MD, PhD, Department of Obstetrics and Gynecology, University of Oulu
    • Marja Ojaniemi, Associate Professor, Department of Paediatrics, University of Oulu
    • Jaana Nevalainen, MD, PhD, Department of Obstetrics and Gynecology, University of Oulu
     

    How to find us

    Department of Obstetrics and Gynecology
    PEDEGO Research Unit
    Medical Research Center Oulu
    Oulu University Hospital
    University of Oulu, FINLAND
     
    terhi.piltonen[at]oulu.fi

     

    Last updated: 6.4.2021