ABSTRACT
Purpose: After the age of fifty years, the incidence of osteoarthritis (OA) increases rapidly in women, suggesting an effect of menopause on the development of OA. Because it is still unclear how menopause precisely influences the development of OA, we aim to investigate this in a novel human model: the Females discontinuing Oral Contraceptives Use at Menopausal age (FOCUM) model. This model consists of women between fifty and sixty years of age, who are currently using a combined oral contraceptive (OC) and aim to stop OC use at short term. When these women stop using OC, a rapid change in hormones is expected, modelling a “sudden menopause”. Therefore, this model provides an opportunity to study changes occurring during menopausal transition. Because the FOCUM model is new, it is unknown if women want to participate, are willing to stop OC use shortly, and will not start hormone replacement after stopping OC use. Therefore, we aim to investigate the feasibility of the FOCUM study. We define the study to be feasible when: 1) 50 participants are included within one year and received their baseline measurements (including questionnaires, blood samples and Magnetic Resonance Imaging (MRI) assessments), 2) the loss of follow-up at 6 weeks is less than 5%, and 3) no hormone replacement therapy is used by the participants at 6 weeks follow-up. Methods: For the inclusion of participants, pharmacies in and nearby Rotterdam were invited to participate. Pharmacies were asked to search in their information systems to identify all possible eligible subjects, based on age and OC use. All eligible subjects received an invitation letter with information about the study. Interested subjects were contacted by the researchers for more information. Inclusion criteria were: 1) woman, 2) between 50 and 60 years of age, 3) currently using a combined OC (with Anatomical Therapeutic Chemical (ATC) code G03AA or G03AB), and 4) started OC use before the age of 45. Exclusion criteria were: 1) already known with osteoarthritis (self-reported or registered by their general practitioner), 2) already known with another inflammatory rheumatic condition, 3) having a contra-indication for MRI assessment, 4) having a terminal or mental illness, and 5) not being able to give informed consent. In this study, measurements are performed at baseline, just before stopping OC use (T0 = 0 to 30 days), and after (T1 = 6 weeks;T2 = 6 months;T3 = 1 year;T4 = 2 years) stopping OC use. At every time point, a digital questionnaire is filled in and a blood sample is drawn. At T0 and T4, also an MRI of one of the knees is performed. Results: In January 2020, invitations were sent to 106 pharmacies of which 48 were willing to participate. Due to COVID restrictions, the first invitations to possible eligible subjects were sent in July 2020. Until April 2021, a total of 1037 invitation letters were sent. 206 subjects replied positively, of which 175 were screened by the researchers. After screening for in- and exclusion criteria, 85 subjects were eligible. The most common reason why subjects were not eligible, was because they did not use their OC anymore. Eventually, 54 subjects gave informed consent and were all seen for their baseline measurements between August 2020 and July 2021. All baseline questionnaires, blood samples and MRI assessments were available. At 6 weeks follow-up, all 54 subjects were still participating in the study. From one participant the blood sample has not been drawn at 6 weeks follow-up and one participant started hormone replacement therapy after baseline measurements (see flowchart 1). [Formula presented] Conclusions: We reached the number of 54 participants within one year, which is more than the initially targeted number of 50. All baseline measurements, including questionnaires, blood samples and MRI assessments, have been collected from these 54 participants. At 6 weeks follow-up, there was no loss of follow-up, of one participant no blood sample was available and one participant started hormone replacement therapy. Therefore, we conclude that the FOCUM study is feasible. The next step will be to investigate differences in cardiometabolic and inflammatory biomarkers, joint complaints and structural OA features between baseline and follow-up measurements.