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

Research group information

Unit and faculty

PEDEGO
Faculty of Medicine

Contact information

Research group leader

  • Professor
    Terhi Piltonen

Research group description

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).

Our team

Where are we headed

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

Our main collaborators

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