Uterine fibroids and endometriosis are two frequent diseases among women of reproductive age. They can be responsible for chronic and/or menstrual pelvic pain and abnormal uterine bleeding. The first-line management of these conditions relies on medical treatment. Hormonal treatment with contraceptive pill can be effective, although up to 30% of patients do not respond to this line of treatment. In this context, GnRH antagonists have been introduced. By suppressing ovulation, they inhibit the action of the gonadal axis and thus can reduce bleeding and pain associated with uterine fibroids and endometriosis. More recently, the GnRH antagonist known as Relugolix has been associated with a low-dose oestradiol and progesteron-line molecule, a medication known as Ryeqo. The goal of this type of treatment is to suppress ovulation while also minimizing symptôms which may derive from lack of oestrogen and progesterone in reproductive age women.
While Ryeqo's efficacy has been proven by multiple large randomized controlled trials, its impact on blood coagulation has yet to be determined. Venous thromboembolism (VTE) is the main, potentially fatal, dleterious effect of oestrogen-containing hormonal treatmen, such as combined oral contraceptives (COC). Several epidemiological studies have found a 3-6 increase in the risk of VTE among women on COC. The thrombogenic risk can be assessed by measuring specific blood biomarkers, which are known to be correlated to the thrombogenic phenotype and allow an overview of the VTE risk prior to conducting large population-scale studies directly measuring the adverse event's prevalence.
The aim of this study is to document the effects of Ryeqo® on hemostasis parameters in order to estimate the risk of VTE associated with its employ. An improved understanding of the VTE risk associated with Ryeqo® will allow to adapt hormonal treatment based on each woman's personal risk profile.
The study will be explained to all women whose medical condition allows the prescription of Ryeqo. All women who give their consent to participate in the study will have a urinary pregnancy test and a blood sample drawn before beginning treatment with Ryeqo. A second visit will be scheduled at 3 months, throughout which a second blood sample will be drawn. A questionnaire including socio-demographic data and clinical symptoms will be completed both on the first and the second visit.
Women consulting at the DFEA of the HUG, who are prescribed Ryeqo® for a qualified medical condition
Age ≥ 18 years
Unable to speak and/or read French
Having used either an oestro-progestin pill (oral, patch or vaginal ring) or oral estrogens in the past 3 months, or DMPA or nomegestrol acetate
Women not having given their consent to participate in the study
Single group
Ryeqo treatment
DrugRyeqo treatment will be administered and hemostasis markers will be measured at T0 and T1
Change from baseline in the mean value of normalized activated protein C resistance (nAPCsr) at 3 months of treatment with Ryeqo
Blood dosage of normalized activated protein C resistance (nAPCsr)
Mean change from baseline to 3 months of treament in the value of sexual hormone-binding globulin (SHBG)
Mean value of SHBG as expressed in nmol/l units
Mean change from baseline to 3 months of treament in the value of normalized thrombomodulin sensitivity ratios (nTMSR)
Mean value of nTMSR as expressed as ratio
Mean change from baseline to 3 months of treament in the value of D-Dimers
Mean value of D-dimers as expressed with ng/ml units
Mean change from baseline to 3 months of treament in the value of thrombin generation markers
Mean value of thrombin generation markers, such as : thrombin generation markers * endogenous thrombin potential (ETP), expressed in nMxmin * peak value, expressed in nM * time to peak, expressed in min * lag time, expressed in min
Mean days of headache at 3 months of treatment
Number of participants having headache and, if so, mean numberof days spent experiencing headache
Mean number of days with pelvic pain at 3 months of treatment
Number of participants experiencing pelvic pain and, if so, mean number of days spent with pelvic pain
Mean difference from baseline on the Higham scale of bleeding at 3 months of treatment
There is no minimum or maximum value. A score inferior to 100 indicates normal flow, a score of 100 or more suggests heavy bleeding, and a score of 150 or more signifies heavy bleeding
Mean number of days of experiencing hot flush
Number of participants experiecing hot flush and, if so, mean number of days spent experiecing hot flush
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