This study will explore the role of oral contraceptive pills in managing uterine bleeding in
women who have low blood platelet counts as a result of aplastic anemia. Oral contraceptive
pills have been shown to be effective in managing uterine bleeding in healthy women, but the
effects have not been thoroughly studied in women who have low platelet counts. The purpose
of the study is to determine whether oral contraceptive pills are a useful complement to
platelet transfusions in women with aplastic anemia and uterine bleeding.
Volunteers for this study must be women between 12 and 55 years of age who have been
diagnosed with aplastic anemia (with a platelet count of less than 50,000/microl) and
currently have active uterine bleeding. Candidates must not be pregnant or breastfeeding,
must have a uterus and at least one functioning ovary, and must be willing to use
nonhormonal methods of birth control (such as condoms or a diaphragm) for the duration of
the study. On the first visit, candidates will be screened with a complete medical history
(including obstetric and gynecological history) and will undergo a physical examination, a
pelvic exam and a pelvic ultrasound. Blood and urine samples will also be taken on this
The study will last approximately two weeks. Participants will be asked to monitor their
medication doses and severity of bleeding during the course of the study. After the first
visit, participants will be separated into two randomized groups and will receive either one
tablet of oral contraceptive or a placebo twice daily, to be taken 12 hours apart at the
same times each day. Participants will also receive platelet transfusions as needed to
ensure that their platelet counts remain over 20,000/microl. After seven days, researchers
will assess participants' uterine bleeding and all participants will be given oral
contraceptives in the second week of the study. Participants whose bleeding has decreased
will receive only one tablet; participants who still have moderate to severe uterine
bleeding will receive two tablets. A final assessment will be performed on day 14 of the
Low platelet counts can occur as a result of blood diseases like bone marrow failure, or
from undergoing procedures such as chemotherapy treatment or stem cell transplantation. A
major complication of low platelet counts in reproductive aged women is uterine bleeding,
which can be life threatening. Sometimes this bleeding begins with a normal menstrual cycle
but may start unexpectedly. In either instance, stopping uterine bleeding not only requires
blood products including platelets but also hormonal treatments.
The hormones estrogen or progesterone can aid in this setting presumably by promoting
endometrial angiogenesis. Continuous oral contraceptive pills (OCP) have been shown to be
very effective in the management of heavy menstrual bleeding in healthy women, but few
studies have been carried out in women with low platelet counts. Moreover, they have few
side-effects and are contraceptive. High-dose intravenous Premarin is also useful but only
for a couple of days after which heavy bleeding will ensue. Progestin hormones are similarly
effective and are also contraceptive.
Oral contraceptive pills are routinely used to control uterine bleeding in thrombocytopenia
secondary to bone marrow failure, chemotherapy and/or stem cell transplantation, during
episodes of severe thrombocytopenia. There are no current data supporting whether the use of
hormonal management is necessary in addition to platelet transfusion. We expect to show that
using continuous OCP in addition to having platelet transfusions will result in a better and
more rapid control of uterine bleeding than having platelet transfusions only.
Eligible subjects will be hemodynamically stable, menstruating women aged 12-55, who have
bone marrow failure, or are undergoing chemotherapy and/or stem cell transplantation for
other diseases with platelet levels less than 50,000 microliters and present with heavy
menstrual bleeding which is expected to last at least 2 weeks. Subjects will be randomized
to either continuous OCP (Lo-ovral) 1 tablet twice daily or placebo twice daily for one
week. All subjects will receive platelet transfusions to keep platelet levels above 20,000
microliters throughout the study. After one week, all subjects who continue to bleed will
receive continuous OCP 1 tablet twice daily. Those who have stopped bleeding will receive
continuous OCP 1 tablet daily. Treatments will be compared for the proportion who stop
vaginal bleeding 7 and 14 days after starting treatment.
- INCLUSION CRITERIA:
Women aged 12-55 years who have a uterus and at least one functioning ovary.
Women with any active uterine bleeding more than spotting
Diagnosed with bone marrow failure, and other disease that require treatment with
chemotherapy or stem cell transplantation with platelet counts less than 50,000
microliters at study entry
Do not desire pregnancy for the duration of the study.
Willing and able to give informed consent.
Willing and able to comply with study requirements.
Age less than 12 years
Hormone level in menopausal range: FSH greater than 40 IU/L, E (2) less than 20 pg/ml
History of liver disease that precludes OCP use
History of thrombosis, thromboembolism and/or thrombophilia.
Currently on 2 or more tablets of any oral contraceptive pills per day at study entry
Having 2 or more DMPA injections in the past 12 months or having DMPA injection in the
past 90 days
Leuprolide acetate injection in the past 30 days
Smoker over the age of 35
Women with estrogen dependent tumor e.g. breast cancer.
Underlying sickle cell anemia
Women who are taking chemotherapeutic agents known to cause ovarian failure such as
Allergy to any medication in this protocol