English Version Nov. 2003 Santiago, Chile
In 2003, the International Federation of Gynecology and Obstetrics (FIGO) decided to devote an entire supplement of its official publication, the International Journal of Gynecology and Obstetrics, to the subject of quinacrine sterilization (QS). This 159-page issue appeared on October 15, 2003. It includes 25 articles from 14 countries and reports on 40,242 cases. It was distributed at the XVII FIGO World Congress, November 2-7, 2003, in Santiago, Chile, a conference attended by some 8,500 obstetrician-gynecologists.
Title:
Quinacrine Non-Surgical Female Sterilization (QS) In A Private Office Practice
Author:
R.B. Whitney, M.D.
Medical Director
Family Planning Center, Florida, USA
INTRODUCTION
· HISTORY
OF QUINACRINE HYDROCHLORIDE
Quinacrine hydrochloride is a synthetic yellow dye and antibiotic manufactured
in powder form for medical usage. It has been available since the 1920’s
and was used extensively in oral tablet form as an anti-malarial prophylactic & treatment
in U.S. service men and women during World War 2 (as much as 36,500 to 52,000
mg. per year per person). A great deal of research on its oral usage has shown
it to be very safe in doses under 3000 mg per month; millions of American and
foreign children have taken the drug for the intestinal parasite, Giardia,
and it remains the only FDA approved drug for this purpose. Doctors around
the world continue to use it for these and other medical conditions such as
lupus and tapeworm. Unfortunately, the drug’s manufacture in the U.S.
was discontinued in the mid 90’s, and our FDA has refused to allow the
importation from a Swiss manufacturer of inexpensive, previously made Q pellets
for the sterilization procedure. Thus, at present, the powder must be imported
and “compounding” pharmacies are then able to laboriously make
much more expensive pellets for the IUD-like insertion process. Dr. Stephen
Mumford, Dr.P.H., president and director of the Center for Research on Population
and Security, one of the three noted American scientists advocating QS, is
the supplier of the pellets for international trials.
· INTERNATIONAL EXPERIENCE
In the past 25 years, more than 140,000 women in 34 countries have
undergone the quinacrine pellet intrauterine sterilization procedure.
This technique,
with its unquestionable safety, simplicity, good efficacy, and low
cost, has primarily been offered in third world countries. Both the
IFFH (International
Federation for Family Health) and FHI (Family Health International)
have endorsed
research into this method.
·
QS DEVELOPMENT & TECHNIQUE…DR. JAIME ZIPPER
The QS method was developed in Chile in the late 70’s by Dr. Jaime Zipper,
the inventor of the Copper--T IUD, and after some trial and error, the optimal
dose for trans-cervical insertion of the pellets was found to be 252 mg. in
7 pellets ejected from the modified copper IUD inserter high in the uterus
about .5 to 1 cm from the fundus with the sheath held steady at that depth
(slide 1). This must be done twice: in consecutive months, and in the week
following a menses (slide 2). If the woman is using the depo-mpa method of
contraception, which may enhance the success of the technique, there may be
no menses to guide one. It is important to the success or efficacy that there
be no blood in the uterus, as this interferes with the action of the quinacrine.
Concentrations of quinacrine in the uterus after insertion are higher than
for oral administration for only a matter of a few hours, but they are adequate
to cause a significant chemical endometritis from which the thick endometrium
always recovers. However, with proper flow into the proximal tubes where the
mucosal lining is only a single cell thick (slide 3), recovery is unlikely
and scar tissue “plugs” develop to obstruct any future access
of sperm to ovum (slide 4).
· AMERICAN HISTORY
It is only within the last five years that three American advocates,
all internationally respected scientists, began to focus efforts
to bring the
method into the mainstream
of reproductive control choices in the United States.
- FDA Modernization Act of 1997 Pharmacy Compounding Provisions: became effective
November 1998, thus enabling American physicians to offer QS
to their private patients with individual prescriptions filled by “compounding” pharmacists.
- 2000: FDA approval of an investigational new drug trial application
for the intra-uterine QS technique: clinical evaluation in U.S women.
- Jack Lippes, m.d. : Dr. Lippes, inventor of the famed Lippes loop intra-uterine
device, and now principal investigator with the FDA, has recently completed
a phase one trial with ten women. A national trial is expected soon.
RISKS AND THE OPPOSITION
·
DETRACTORS’ UNPROVEN SUPPOSITIONS
Many of the method’s detractors express concern about possible
increased likelihood for cancer, ectopic pregnancy, and birth defects
in any subsequent
pregnancies. We know there are none of these risks with oral consumption
of the drug-- at much higher doses than used in the sterilization
process-- and pathology studies suggest that if the quinacrine
reaches the fallopian
tubes, it closes them completely (7). The risk of ectopic pregnancy
following failure of surgical sterilization in the U.S. is higher
than for QS,
using newer insertion technique. Every year in my country there
are about a dozen
deaths and about a thousand hospitalizations from complications
of surgical sterilization. There has never been a death recorded
with the QS pellet
method---a remarkable safety record! ! This includes the rare case
of uterine perforation
with the inserter and depositing the pellets in the peritoneal
cavity. Although painful, once the quinacrine is absorbed, pain
diminishes and
there are no
other sequellae (8).
Antagonists make much of the fact that quinacrine is a mutagen
(so is tetracycline) and would have others believe such drugs can
cause
cancer
because of this
factor. Direct evidence of quinacrine carcinogenicity in humans
or animals has never been established. Finally, the drug does not
appear
to be terratogenic.
In a 31,781 case Vietnamese trial, “there were two cases
of quinacrine insertion during early pregnancy. One was a case
of ectopic pregnancy,
and the other woman gave birth after the study cut-off date. The
infant was normal
(9). There are some animal data for both monkeys and rats showing
that exposure of the fetus at the time of embryogenesis leads to
resorption
or abortion,
especially in early gestation, but there was no evidence for treatment-related
malformations (7). Nevertheless, fierce opposition from certain
quarters has led several countries to suspend their programs.
·
DR. MALCOLM POTTS, GUISEPPE BENAGIANO, & W.H.O.
Some detractors still insist on expensive and time-consuming
animal research before using women as subjects. Other investigators,
among
them Malcolm
Potts and Giuseppe Benagiano, have stated these “cannot prove human safety”.
They also observed that such animal tests can produce results “qualitatively
different from those subsequently found in humans, as occurred with Depo-Provera”(1).
It is interesting to note that for many years, the World Health Organization
(WHO), under the direction of Dr. Benagiano, opposed QS. In the above commentary,
the authors note a cumulative low risk of serious, immediate side effects,
but insufficient data to answer questions about potentially important, long
term side effects. They are glad FDA trials are underway, but, while admitting
the safety answer lies in “a very large scale of controlled use”,
they cautiously advise offering QS only to women who ask for sterilization
and “for whom existing methods are not available” or who “present
unacceptable risks”. A very conservative and limiting “middle
road” indeed!
AUTHOR’S AMERICAN EXPERIENCE
· ELEVEN QS PROCEDURES (2000 TO PRESENT)
The 11 women, ranging in ages from their late 20s to their early
40s, have tolerated the two insertions very well, with minimal
side effects:
mainly
low back and/or abdominal ache. None have required pain medications,
had fever or headache, or missed any daily activities, such as
work, afterwards.
Nine are Caucasian, one is Hispanic, and one is East Indian ---
all without insurance coverage. They have been extremely pleased
with
the method.
I will continue to follow them at 6-month intervals. Questions
asked of them recently
have produced negative responses about: 1) adverse menstrual
changes, such as a missed period followed by a heavy/crampy one
(which could
be an early
miscarriage); 2) sexual discomfort; 3) any changes or abnormal
feelings in the abdomen.
I use the IFFH sterilization register and follow-up to record
my cases, and have developed my own office protocol for information
calls, workup,
and
history and physical exam forms. My consent form is extensive
and
only slightly modified from that developed by Dr. Mumford and
others. I
have Spanish translations
of everything, including a training manual for providers.
· A FEW PRACTICE POINTS…
- Sedation before insertion is unnecessary, but one might wish to
do an anterior cervical lip anesthetic injection for the tenaculum (I use
a sharp toothed one), or an atraumatic instrument.
- Be certain of the position of the uterus in the body in the initial
bimanual pelvic exam. When sounding to the fundus, try a gentle rotation
or side-to-side motion of the sound to see if there might be a septum.
- Immediately after insertion, the woman should lie down on a couch
or bed so as to maximize the uterine fundal position downward. We are experimenting
with a long foam wedge to facilitate this (slide 5). and hopefully make
more of the quinacrine available to the cornuae.
- After 30 minutes, one can see thru a reasonably full bladder with
ultrasound whether there is quinacrine flowing to the cornuae.
- With the second insertion, one may encounter some immediate cervical
bleeding on sounding, probably a residual of the quinacrine inflammatory
effect of the previous insertion. I do not consider this a contra-indication
to continuing
with the insertion.
· FEMINIST CHALLENGE TO MY LICENSE
In early 2002, 4 women ( mostly radical feminists and sociologists
from a New England college ) brought a complaint against my medical
license
re my
advertising and practicing QS. There was absolutely no scientific
merit whatsoever, and the complaint was investigated by the Agency for
Health
Care Administration
and the Florida Department of Health. On 17 October 02, a letter
was written to my attorney stating: “Please be advised that the complaint in the
matter referenced above has been investigated and reviewed by the Probable
Cause Panel of the Board of Medicine. Pursuant to section 456.073(9)(c),
Florida statutes, the panel found that there was insufficient evidence to
support prosecution and directed the case be dismissed.” These
same women also oppose our FDA even investigating the validity and
safety of
QS with Dr. Lippes !!
DISCUSSION: UTERINE ANOMALIES AND FAILURE RATE
I suspect that some of our -/+ 5% failure rate may be due to uterine
anomalies, the most likely of which is some degree of intrauterine
septum (slide 6).
Various authors have estimated the incidence of anomalies as high
as 10% (2) (3) , but in my 35 years’ gyn experience with IUDs and abortion,
I believe some septum to be about 5%. Now we have 3-D vaginal ultrasound
to more accurately differentiate between a significant septum and a bicornuate
or arcuate uterus (slide 7), and also to better define the QS cornual scar
tissue (4)(5). Patients who have had significant pregnancy wastage or premature
labor and delivery may be good candidates for both pelvic and abdominal 3-D
sonography, for many studies have often shown ipsi-lateral agenesis of a
kidney with uterine body malformations (6). Any QS failure should have an
ultrasound study, and it would be very beneficial if all first insertions
had access to at least a reasonably good resolution machine to check for
symmetry of flow of “Q” toward the cornuae. I also suspect there
is a majority of fundal septae which are insignificantly shallow, or less
than 2 cm deep and would not likely cause pregnancy wastage. They might,
however, deflect the “Q” pellets to one side with high insertion.
Therefore, I have modified my insertion depth to 1 – 2 cm
back from the fundus for a more central ejection.
CONCLUSION
The level of need for contraception in the world is rising rapidly.
To satisfy the U.N. median variant population projection of 12
billion people
at the
end of the 21st century, we must achieve by 2035 a replacement
fertility rate of 2.1 children per woman. The UNFPA estimates that
this will
require 200 million sterilizations in the 10 years ending in 2005,
or two years
from now. About 85% of these were projected to be female, the rest
vasectomies. Given this situation, it is obvious that there is
urgent need for a safe,
effective, inexpensive method of sterilization that can be delivered
by paramedical
personnel in rural areas (10). QS may be the answer, and a wide,
controlled clinical study with good patient information and consent,
combined
with a parallel, retro-study of previous patients mentioned above,
should
be implemented
immediately. In the U.S.A., our society’s litigious nature
will be a severe restraint unless or until the FDA gives its seal
of approval
to
this remarkable method. Meanwhile, Dr. Mumford and others have
been informing clinicians about QS at their professional meetings.
The response
has been
gratifying, but we need more American physicians actively involved
with office patients.
IT IS TIME FOR QS TO BE MADE AVAILABLE TO WOMEN EVERYWHERE! I
HOPE YOU WILL JOIN US IN OFFERING IT TO THEM. THANK YOU!
YA ES HORA PARA QUE LA QUINACRINA SEA DISPONIBLE PARA LAS MUJERES
EN TODAS PARTES DEL MUNDO! ESPERO QUE USTEDES NOS ACOMPAÑEN A OFRECER ÉSTO
A ELLAS--- GRACIAS!!
References:
1) |
POTTS M, BENAGIANO G : QUINACRINE STERILIZATION: A MIDDLE ROAD [COMMENTARY
IN CONTRACEPTION 64 (2001): 275-276]
|
2) |
DACOSTA V, ET AL : SUCCESSFUL PREGNANCY AFTER HYSTEROSCOPIC METROPLASTY.
WEST INDIAN MED J 2002 DEC. 51 (4) :260-2 |
3) |
ZABAK K, ET AL : SEPTATE UTERUS AND REPRODUCTION DISORDERS: CURRENT OF HYSTEROSCOPIC
SEPTOPLASTY. GYNECOL OBSTET FERTIL 2001 NOV. 29 (11) : 829-40 |
4) |
WU MH, ET AL : DETECTION OF MULERIAN DUCT ANOMALIES USING THREE-DIMENSIONAL
ULTRASOUND. J CLIN ULTRASOUND 1997 NOV-DEC. 25 (9) : 487-92 |
5) |
SHETH S, SONKAWDE R : UTERINE SEPTUM MISDIAGNOSED ON HYSTEROSALPINGOGRAM
INT JL GYN & OB. 69 (2000) : 261-63
|
6) |
FRIED AM, ET AL : UTERINE ANOMALIES ASSOCIATED WITH RENAL AGENESIS: ROLE
OF GRAY SCALE ULTRASONOGRAPHY. AM JL ROENT 1978 DEC. 131 (6) : 973-5 |
7) |
KESSEL E : QUINACRINE STERILIZATION: AN ASSESSMENT OF RISKS FOR ECTOPIC
PREGNANCY, BIRTH DEFECTS AND CANCER. ADVANCES IN CONTRACEPTION, ‘98;
14:81-90 |
8) |
LIPPES J : QUINACRINE STERILIZATION SAFETY AND EFFICACY. AMERICAN PUBLIC
HEALTH ASSOCIATION ANNUAL MEETING, CHICAGO, IL.. NOV. 8,1999 |
9) |
HIEU DT ETAL: 31,781 CASES OF NON-SURGICAL FEMALE STERILIZATION WITH QUINACRINE
PELLETS IN VIETNAM THE LANCET 342 (JULY 24,1993) : 213-217 |
10) |
BLACK T : THE QUINACRINE IMPERATIVE. MARIE STOPES INTERNATIONAL, LONDON |
Quinacrine changed my life!
The procedure was essentially painless, affordable, and freeing!
I love my new lifestyle.
Thank you, Dr. Whitney!"
-B.H.