Treatment of Prolonged Uterine Bleeding of Etonogestrel (ENG)-Releasing Implant
Status:
Not yet recruiting
Trial end date:
2022-04-01
Target enrollment:
Participant gender:
Summary
Long-acting reversible contraceptives [LARC; copper-intrauterine devices (IUDs), the
levonorgestrel-releasing intrauterine system (LNG-IUS) and subdermal implants] are the most
effective reversible contraceptives available. A common side effect of these methods is
changes in menstrual bleeding. Dissatisfaction with unpredictable bleeding is the main reason
for early discontinuation of LARC methods.
The mechanism of unpredictable bleeding is unknown; it is likely related to the progestogen
dilating superficial veins and capillaries, which are fragile and susceptible to focal
bleeding. Other potential influences include changes in structural support of the
endometrium, altered matrix metalloproteinase activity, and changes in endometrial perfusion
and hemostasis. Local genetic alterations of the hormonal receptors of endometrium can also
play a role in the etiology of the unpredictable bleeding experienced by some women.
Regarding etonogestrel (ENG)-releasing implant, some evidences suggest that the use of
mefenamic acid, mifepristone with estradiol or doxycycline, or doxycycline alone can
temporally stop the bleeding; however, all these therapies cannot avert the recurrence of the
bleeding. Recently, a randomized clinical trial (RCT) evaluated the effectiveness of a
short-term use of combined oral contraceptive (COC) in stopping bleeding episodes and
preventing bleeding recurrence. The authors found that bothersome bleeding in ENG-implant
users stopped within 14-day of COC treatment, but bleeding most often resumes within 10 days
of treatment cessation.
Although COC can stop the bleeding, it is not known which component of the COC is responsible
for this effect. There is evidence suggesting that estrogen alone is not effective in
stopping the bleeding of progestogen-only contraceptives or a high dose of ethinyl estradiol
is needed to obtain this effect. Furthermore, the recurrence of the bleeding shown with the
COC use could be explained by the interruption of the estrogen. For this reason, our
hypothesis is that a progestogen-only pill could be superior to placebo in stopping the
bleeding associated with the ENG-implant use as well as being superior to placebo in
recurrence of bleeding after discontinuation of the therapy.