Estetrol drospirenone effective as firstline endometriosis treatment: Study
Endometriosis is a chronic inflammatory condition affecting
women of reproductive age that worsens their quality of life (QoL) because of
various chronic pelvic pain symptoms, including dysmenorrhea, intermenstrual
lower abdominal and back pain, defecation pain, and dyspareunia. Guidelines
recommend combination estrogen and progestin drugs as the first-line therapy.
Ethinyl estradiol (EE), a widely used estrogen in combined oral contraceptives
(OCs), affects the vascular endothelium and liver protein synthesis related to
hemostasis and blood pressure, increasing the risk of cardiovascular
complications. Estetrol (E4) is a native estrogen produced in fetal liver that
specifically binds to estrogen receptors (ERs) a and b. Estradiol activates
both nuclear and membrane ERa equally, whereas E4 acts as an agonist of nuclear
ERa and an ERa-dependent membrane-initiated steroid signaling antagonist.
Therefore, E4 was termed the first native estrogen with selective tissue
activity and was classified differently from selective ER modulators. The
combination of E4 (15 mg)/drospirenone (DRSP) (3 mg) achieved sufficient
ovulation suppression, with a low frequency of unscheduled bleeding and minimal
effects on lipid and glucose metabolism and hemostasis.
Estetrol/drospirenone has lower estrogenic activity than
EE-based OCs, possibly with decreased thromboembolic risk. To evaluate the
efficacy and safety of 24-week cyclic administration of estetrol (E4) (15
mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis, a
24-week, multicenter, randomized, double-blind, placebo-controlled,
parallel-group study was carried across Twenty-five study centers in Japan. A
total of 162 Japanese women were diagnosed with endometriosis. Participants
were randomly allocated to the E4/DRSP group or the placebo group. In the
E4/DRSP group, participants were orally administered one tablet containing E4
(15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4
days for a hormone-free interval, constituting a 1-cycle regimen. One placebo
tablet was administered once daily for 28 days to participants in the placebo
group. The treatments were continued for six cycles (24 weeks) throughout the
confirmatory period. Changes in visual analogue scale (VAS) scores for the most
severe pelvic pain (lower abdominal and back pain) from baseline to six
treatment cycles at the end of the confirmatory study period were studied.
Estetrol/drospirenone showed changes in the mean VAS scores
for the most severe pelvic pain from baseline to the end of the 6-cycle
treatment. The between-group difference was significant, showing superiority to
placebo. The responder rates, R30% and R50% reductions in the VAS scores from
baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs.
29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac,
pelvic tenderness, and limited uterine mobility) were significantly improved by
E4/DRSP treatment, and the proportions of stable and worsened participants were
significantly lower than in the placebo group.
Estetrol/drospirenone decreased the size of endometriomas
and improved quality of life, on the basis of quality of life–related
questionnaires and global impression scores. No safety concerns were observed
with E4/DRSP treatment. Few differences were observed in the proportion of
participants with hemostasis parameters outside the reference range between the
E4/DRSP and placebo groups.
Endometriosis and its associated symptoms negatively affect
educational attainment, work productivity, career choices and success, social
life and activities, family choices, personal relationships, mental and
emotional health, and QoL (21), which may alter women’s life course
trajectories. Furthermore, there is often a prolonged delay from symptom onset
to diagnosis and treatment of endometriosis, increasing the impact on the life
course. Therefore, early diagnosis, effective intervention, and comprehensive
care are required to minimize the impact of endometriosis.
This study demonstrated that E4/DRSP is clinically effective
for EAPP treatment, with improved objective gynecological findings, QoL, and
global impressions in patients with endometriosis. Estetrol/drospirenone should
be considered a firstline endometriosis treatment.
Source: Tasuku Harada, M.D., Ph.D.,a Takao Kobayashi, M.D.,
Ph.D.,b Akihiro Hirakawa; Fertil Steril® Vol. 122, No. 5, November 2024
https://doi.org/10.1016/j.fertnstert.2024.07.011
