Hormonal Regulation of Cardiometabolic Health (HoCa)

The overarching aim of the HoCa study is to understand how loss of ovarian function affects health and well-being. The HoCa study focuses on revealing the effects of oophorectomy, i.e., surgical removal of ovaries resulting in immediate menopause, on quality of life, cardiometabolic health, central nervous system functioning and adipose tissue biology.

Table of contents

Project duration
-
Core fields of research
Physical activity, health and wellbeing
Research areas
JYU.Well
Physical activity through life span
Physical activity, wellbeing and behaviour change across the life-span
Molecular mechanisms of exercise and health
Neuromuscular function and adaptation
Active aging
Co-operation
Laakkonen's research group, the MENSA study, the CURE3D lab (Department of Cardiac Surgery, University Hospital Düsseldorf, Germany), Central Finland, Pirkanmaa, North Savo, Southwest Finland and North Ostrobothnia Wellbeing Services Counties, and HUS
Faculty
Faculty of Sport and Health Sciences
Funding
Research Council of Finland
(applied), the Novo Nordisk Foundation (term: 1.1.2025-31.12.2027)

Project description

The overarching aim of the HoCa study is to understand how loss of ovarian function affects health and well-being. The HoCa study focuses on revealing the effects of oophorectomy, i.e., surgical removal of ovaries resulting in immediate menopause, on quality of life, cardiometabolic health, central nervous system functioning and adipose tissue biology.

HoCa is a multidisciplinary research project that not only investigates the molecular regulatory pathways orchestrating physiological consequences of menopause but also performs qualitative interviews, allowing women’s perspectives, interpretations and feelings about surgically induced menopause to be heard. By combining clinical data with advanced 3D adipose tissue models, HoCa offers a unique human-based approach to studying hormonal regulation, immune function, and metabolic health.

HoCa combines three research components:

  • A clinical study with women undergoing surgical menopause (ovary removal).
  • A qualitative interview study with a sub-sample of the clinical study participants.
  • A laboratory study using 3D adipose tissue models called adipoids, grown from human fat samples.
     

In the clinical study, we follow participants before and after surgery. Because the exact timing of estrogen loss is known, this design allows us to study its effects in a controlled way. We measure body composition, physical performance, central neural system functioning, metabolism, and quality of life. Blood samples are collected to analyze biomarkers such as non-coding RNAs and metabolic compounds related to cardiometabolic health.

At the same time, we develop 3D adipose organoids (adipoids) from fat samples taken during surgery. These organoids are grown from both visceral (deep abdominal) and subcutaneous (under-the-skin) fat. They closely mimic real human fat tissue and contain fat cells, immune cells, and structural cells, making them well-suited for testing how different fat depots respond to hormonal changes.

In lab experiments, these organoids are exposed to blood serum from pre- and postmenopausal women, pure estradiol (E2), or exercise-mimicking compounds such as AICAR or metformin. This allows us to assess changes in adipocyte cell structure, fat metabolism, inflammation, and immune cell composition.

By combining clinical data with organoid experiments, HoCa provides a detailed view of how menopause affects women’s adipose tissue and metabolism, and helps explore whether hormonal or pharmacological treatments can reduce health risks that increase after menopause.

We also interview women before and after the surgeries. This allows us to understand the reasoning process women go through, how they picture the process, who the significant contributors are and how they experience the whole process. it is important to understand how surgically induced menopause is received by women who experience it to be able to offer better, personalised care. 

Current state and recent news

Desing, methods and data

Repeated measurement for about 120 women undergoing ovarian removal. Quite often, these operations are done to healthy women with a genetic predisposition to ovarian cancer, such as Lynch syndrome, BRCA1 and BRCA2 carriers.

Timepoints:
• before surgery (baseline)
• 1 to 2 months after surgery
• 12 months after surgery

Participation in HoCa includes at least two visits to the Ä¢¹½Ö±²¥ labs at each of the three time points. However, it is also possible to participate solely by filling out the questionnaires without any laboratory visits.

What we measure:

  1. Body composition: DXA scan, bioimpedance
  2. Vascular and metabolic health:
    • Blood pressure, lipid profile, glucose tolerance
    • Energy expenditure (at rest and during exercise)
  3. Physical performance and physical activity
  4. Central nervous system function (for a subsample)
  5. Questionnaires:
    • Menopause symptoms
    • Sleep and quality of life
    • Medical and gynaecological history
    • Lifestyle and socioeconomic variables
  6. Blood samples:
    • Hormones, metabolomics, inflammation markers and ncRNA sequencing
  7. Interviews to assess participants' experiences, reasoning and thoughts about surgical menopause (for a subsample)

Cell- and molecular biology laboratory component (Adipoids)

Source: Paired SAT and VAT samples for organoid development
Stimuli: for example, pre- and postmenopausal sera and sex hormones to assess the effects of menopause
Assays:
• Functional profiling: lipid uptake, insulin sensitivity, and cytokine response assays
• Secretome profiling: Olink, Quansys, and ncRNA-sequencing
• Fenotyping: flow cytometry and single-cell RNA sequencing

Eligibility criteria for study participants

  1. Having at least one functional ovary and going to oophorectomy as part of personal health care. If having two functional ovaries, both will be removed.
    • Surgery will induce menopause
    • Removal of other organs, such as fallopian tubes or uterus, does not lead to exclusion.
  2. A person does not have ovarian cancer or current treatment for any cancer.
  3. Age between 35 and 50 years.
  4. Not yet postmenopausal.
  5. Not using systemic estrogen-based medications (hormone therapy or contraception with estrogenic component).

Additionally, health-related issues, such as heart disease, kidney disease, or mobility limitations, may pose an obstacle to performing exercise load tests in the HoCa study. Furthermore, participating in the neurological function measurements is prohibited if the participant has epilepsy, diabetic neuropathy, psychiatric disorder, or another disease that affects the function of the heart and circulatory system, respiratory system, musculoskeletal system, or nervous system (such as stroke, brain haemorrhage, Parkinson's disease, MS disease, etc.). Having a pacemaker, cochlear implant, or any other metal or electronic device implanted in the body also prevents participation. Bioimpedance measurement cannot be performed on individuals with a pacemaker.

Note! Persons who do not qualify as participants for exercise tests or neurological measurements may still be suitable participants for other sections of the HoCa study.

Recruitment for the study will be done across Finland in the following areas:

  1. Wellbeing Services County of Central Finland (Hyvaks)
  2. Wellbeing Services County of Pirkanmaa (Pirha)
  3. Wellbeing Services County of North Savo
  4. Wellbeing Services County of Southwest Finland (Varha)
  5. Wellbeing Services County of North Ostrobothnia (Pohde)
  6. HUS

The HoCa study will start accepting study participants in Autumn 2025.

If you are interested in participating or collaborating with HoCa, please contact Eija Laakkonen or other members of the HoCa working group.

Project team

External members

Elvira Weber

Dr. rer. nat. (CURE3D lab group leader)

Pauliina Aukee

Head of Obstetric and Gynecological Department

Jaana Seikkula

Chief Physician of Obstetric and Gynecological Department

Synnöve Staff

Chief Consultant in Gynaecological Oncology

Niina Norppa

Specialist Physician in Obstetrics and Gynecology

Marjo Tuppurainen

Professor, specialist in obstetrics, gynaecology and gynaecological oncology

Titta Joutsiniemi

Specialist in gynaecological oncology

Seija Ala-Nissilä

Specialist in urogynaecology

Maarit Niinimäki

Chief physician in unit of reproductive medicine

Susanna Savukoski

Specialist Physician in Obstetrics and Gynecology

Hanna Savolainen-Peltonen

Chief Clinician in HUS Gynecology and Obstetrics

Mikko Loukovaara

Physician in charge of the ward, Gynecological Cancer Outpatient Clinic