Ovarian endometriomas (or "chocolate cysts") are present in up to 50% of patients with
endometriosis - a chronic gynecological disorder associated with pain and infertility.
These cysts directly impact fertility and ovarian reserve and can cause additional
symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture,
or more rarely torsion).
While endometriomas tend to require surgical excision for definitive resolution, medical
management with a variety of agents has been shown to be effective in reducing their
size; these agents include combined oral contraceptives (COC), aromatase inhibitors,
progestins, androgens, cabergoline, and gonadotropin-releasing hormone agonists (GnRH-a).
Medical management to reduce their size can help alleviate symptoms indefinitely without
damaging ovarian reserve prior to fertility treatments, or to temporize until surgical
management can be offered. Medical management has become particularly important in light
of the COVID-19 pandemic, with significantly reduced access to surgery, and resource
allocation to alleviate an overburdened healthcare network.
Estetrol/drospirenone (Nextstellis™) is a prescription-only COC available in Canada
containing two hormones: a progestin (drospirenone - well known as both a standalone
contraceptive and in other combined formulations), and an estrogen (estetrol - newly
introduced with this product). While ethinyl estradiol (EE) is the most common estrogen
currently used in COC, estetrol (E4) has proven safety and tolerability, and emerging
evidence points towards a lower risk of thrombosis than traditional EE used in other COC.
Studies have documented efficacy and safety for the combination estetrol/drospirenone,
with a favourable bleeding profile, and very low rates of adverse reactions. While there
exists already encouraging data on drospirenone and drospirenone containing products on
alleviating symptoms of endometriosis and reducing the size of endometriomas, there are
no studies to date evaluating this novel combination of estetrol/drospirenone in managing
ovarian endometriomas.
The primary objective of this study is to determine the effectiveness of
Estetrol/drospirenone, a combined oral contraceptive (COC), in the reduction of ovarian
endometriomas after a 3- and 6-month period of treatment.
This is a single-center, open label, single arm interventional study that will be
performed at the McGill University Health Centre (MUHC) Royal Victoria Hospital (RVH).
Women 18 years of age or older with at least one ovarian endometrioma, of at least 3cm,
who are seeking a hormonal treatment for their endometrioma(s), will be recruited. The
study will aim to recruit 21 women.
Consenting participants will be given a 6-month course of oral estetrol/drospirenone (15
mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration. An
ultrasound assessment of ovarian endometrioma(s) will be performed prior to drug
initiation (baseline), and will be repeated at 3-months and 6-months time. All
ultrasounds will be performed by the same ultrasonographer using a standardized technique
and 3-D volumetric assessment. At each of these hospital visits, participants will have
their weight and blood pressure measured and they will complete questionnaires regarding
their endometriosis symptoms with a research coordinator. Safety, tolerability, and the
incidence of adverse effects will also be monitored at the same time intervals.