Science Student Journal

Ehlers Danlos Syndromes (EDS) are a class of 13 genetically similar inherited connective tissue disorders, typically categorized by joint hypermobility and connective tissue abnormalities. Due to the resulting connective tissue laxity and issues in collagen synthesis, female EDS patients experience higher rates of gynaecological impact such as dysmenorrhea, hypermenorrhea, and menorrhagia. Healthcare providers (HCPs) are increasingly prescribing combination estrogen-progesterone monophasic oral contraceptive pills (OCPs) as the primary method to treat these conditions.

 

While previous studies have demonstrated interactions between sex hormones and collagen, the impacts of increased estrogen and progesterone levels on those with connective tissue disorders, which typically lead to prescription of OCPs, has yet to be studied. This has led to a knowledge gap on how increased hormone levels interact with the pathogenic collagen produced in EDS.  

 

To fill this gap, using CRISPR-Cas9 genome editing, a mouse model can be created to represent classical EDS (cEDS) using known mutations. Using this model, it is then possible to directly analyze the impacts of fourth and second generation combination OCPs on connective tissue in those with cEDS. This can be done using translationally relevant doses in mice of both ethinyl estradiol and drospirenone to mimic fourth generation OCPs, and ethinyl estradiol and levonorgestrel to mimic second generation OCPs. These models can be used to determine if there is any interaction between estrogen, progesterone, and disordered collagen, and to see if these interactions lead to better or worse outcomes long-term in cEDS, and other connective tissue disorder, patients.