1 The overall rate of hysterectomy for all women over the age of 1
5 was 5.4 per 1 000 in 1991 (1). The data contained in Table 1
could not be analyzed by menopausal status, but are presented by
age. In 1991, the highest rate of hysterectomy was for women
between the ages of 45 and 64 (calculated from data in reference
2).

TABLE 1: HYSTERECTOMY RATES PER 1,000 WOMEN IN 1991

Age Hysterectomy Rates

15-44 6.0

45-64 7.5

Over 65 3.1

NCHS Data

*1 Federal hospitals include those of the four armed services, Veteran's hospitals, and Indian Health Service hospitals.  These 8,000 cases are not included in the subsequent data used in this statement.

The last year for which hysterectomies were categorized by whether
or not the ovaries were removed at the same time (bilateral
salpingo-oophorectomy) was 1987. In that year, the overall
percent
of hysterectomy with removal of both ovaries was 45.5 percent;
without removal of ovaries, 54.5 percent (3). Table 2 shows the
change with age.

TABLE 2: PERCENT OF HYSTERECTOMIES WITH REMOVAL OF BOTH OVARIES,
BY
AGE, IN 1987

Age Percent with
Removal of Both
Ovaries

20-29 24.2
30-39 27.7
40-49 57.6
50 and over 61.6
NCHS Data

Information on minority women is sparse, largely historical, and
anecdotal. There are, however, some recent data. One survey of
women in Pittsburgh, ages 40-52, found a prevalence of
hysterectomy
of 23.7 percent in whites but 46.9 percent in Blacks (4) In the
Behavioral Risk Factor Surveillance Survey, a sixteen-state
survey
of women over age 18, higher hysterectomy rates were shown for
women
with less education and lower incomes, but no independent
differences between Blacks and Whites (5).

Reasons for Hysterectomies

In tabulating the number of specific diagnoses for hysterectomy,
the
NCHS has used three-year intervals, the latest of which is 1985-
1987. In Table 3 these data are expressed as percentages of the
total by indication for each age group. Overall, of 1,967,000
hysterectomies during that period, 1 0 percent were for cancer, 6
percent for endometrial hyperplasia (excessive growth of the
uterine
lining), 30 percent for myoma (also known as fibroids), 19
percent
for endometriosis (uterine lining cells growing in abnormal
locations), 16 percent for uterine prolapse (loss of support for
the
pelvic organs), and 19 percent for other conditions such as
chronic
pelvic pain, pelvic inflammatory disease, and obstetrical
complications (6).

TABLE 3: THE INDICATION FOR HYSTERECTOMY BY AGE (PERCENT) IN
1985-

1987.

AGE CANCER HYPER- MYOMA ENDOME UTERINE OTHER
PLASIA TRIOSIS PROLAPSE

15-44 6 3 30 24 12 24
45-55 6 10 45 15 14 10
55+ 31 11 12 3 33 10

Calculated from reference (6)

The more frequent indication for hysterectomy changes
dramatically
with age. For women under 55 years of age, endometriosis and
myoma
are the most common causes of hysterectomy, while for women 55
and
over, cancer and uterine prolapse predominate (6).

Risks Associated With Hysterectomy

Death rates immediately after hysterectomy vary considerably. In
the absence of cancer or pregnancy, rates range from 6 to 11
deaths
per 1 0,000. For obstetrical indications, the reported rates are
28
to 39 per 1 0,000; for cancer patients, reported surgical
mortality
rates relating to hysterectomy range from 70 to 200 per 10,000;
and,
for benign diseases they are estimated to total about 300 deaths
annually in the United States (7).

In a series of studies, the incidence of nonfatal complications
of
hysterectomy ranged from 25 to 50 percent of cases. The most
common
complication is fever (1 5-32 percent) from a respiratory,
urinary,
or wound infection, or an unknown source. Other complications
include hemorrhage requiring transfusion (8-15 percent), injury
to
adjacent organs (0.5-1.4 percent) and pulmonary embolism (blood
clot
to the lungs, 0.2-0.3 percent). In all categories, vaginal
hysterectomy, which does not require an incision in the abdomen,
was
less risky than abdominal (reviewed in reference 7).

A number of long-term effects of hysterectomy have been
described,
but not well documented. There is a significant need for more
data
in this area, particularly with respect to any racial and ethnic
differences. The long-term effects may include premature ovarian
failure, persistent pelvic pain, constipation, urinary symptoms,
fatigue, depression, and diminished sexual interest and response
(7). From the few psychiatric studies on this topic, it appears
that the emotional response to hysterectomy relates to the
woman's
presurgical personality traits, strength of her support system,
and
family history. Studies also suggest that patients at greatest
risk
of depression after hysterectomy are women under 35, those who
have
not had children, those who desire future children, and those who
experienced a postoperative fall in ovarian steroids.

Of particular importance are the long-term effects related to
removal of the ovaries, rather than the uterus itself. These are
the loss of bone which leads to osteoporosis, and a pattern of
serum
lipids (cholesterol and triglycerides) associated with increased
cardiovascular disease risk. These changes are associated with
the
loss of estrogen due to the removal of both ovaries. Estrogen
replacement therapy is effective in ameliorating the bone changes
and reversing the lipid changes seen after removal of both
ovaries
(8).


Recent studies have indicated that prevention of ovarian cancer
alone is not a sufficient justification for removal of the
ovaries
at the time when hysterectomy is performed for other reasons.
The
lifetime risk of death from ovarian cancer for a 50-year-old
women
is 0.8 percent (7). The patient's age, menopausal status, and
willingness to adhere to a hormone replacement therapy regimen
should also be weighed in the decision. Most discussions of the
benefits to the cardiovascular and bone systems of hormone
replacement therapy assume that the patient will take the
medication
perfectly. In reality, medicine-taking behavior in general is
less
than ideal. Leaving the ovaries in has to be weighed against
"preventively" taking them out when followed by hormone
replacement
taken the way people really take medicines. When this is taken
into
account, keeping the ovaries in results in longer calculated
survival (9).

Alternatives to Hysterectomy

Benign Disease. Expectant management, or watchful waiting, is
indicated and appropriate when symptoms of benign disease are not
distressing to the patient and the uterus is not enlarged.
In premenopausal women, conditions such as endometriosis and
myoma
usually stabilize or regress at the time of natural menopause.

Furthermore, recent advances in technology have enabled us to
follow
more closely the status of many conditions which may lead to
hysterectomy. New ways of forming an image of the internal
organs
without X-rays, such as ultrasound with a vaginal probe, and more
recently, magnetic resonance imaging (MRI), are extremely
accurate
and reproducible for measuring and following the size of the
uterus,
the size of myomas, and thickness of the endometrium (uterine
lining).

When the effects of benign disease become more symptomatic, the
usual first line of treatment consists of medical therapies and
conservative surgical approaches (7). Since endometriosis and
myoma
generally require the female hormone estrogen for growth, medical
treatments have centered on medications which interfere with the
effects of estrogen. These include progestins (which resemble
the
ovarian hormone, progesterone), danazol (an anti-hormone), and
more
recently, analogs of gonadotropin releasing hormone (GnRH) (a
brain
hormone involved in reproduction). Abnormal uterine bleeding may
also be treated with steroids or danazol, or with nonsteroidal
anti-
inflammatory agents similar to aspirin (7).

Some patients, however, cannot tolerate the side effects of
steroids
or danazol. GnRH analogs and antiprogestins, a new class of
hormone
blocker, are promising, but have only been used in short term
trials
so far. GnRH analogs, in particular, have produced an overall
reduction in myoma size and uterine size of 40-50 percent, but
the
effects last only as long as therapy is continued. The
low-estrogen
state produced by GnRH analogs, however, limits their usefulness
because it can lead to decreased bone density. Therefore, these
drugs are most useful, for brief periods, as a preparation for
surgery, or if the patient is expected to enter menopause shortly
(7).

Conventional treatment of chronic pelvic pain consists of oral
contraceptives or nonsteroidal anti-inflammatory drugs. This
condition, however, responds even more readily when a multi-
disciplinary strategy is undertaken, including medical,
behavioral,
and other approaches.

There are simple approaches to mild or moderate uterine prolapse.
These include placement of a pessary (an internal device to
support
the uterus mechanically) and exercises to strengthen the pelvic
muscles. Major surgery is usually indicated for severe prolapse.

In the past, total hysterectomy for benign disease has been
justified on several grounds, including; 1) prevention of
future
ovarian cancer (by removal of the ovaries), 2) the fear and
risk
of missing a hidden malignancy, 3) pressure on adjacent organs,
4) increased surgical risk if this operation is postponed until
a
later time, 5) compromised fertility if conservative surgery is
attempted, or 6) risk of worsening the benign disease by
postmenopausal hormone replacement therapy.

There is, however, no convincing evidence that hysterectomy
conveys
a benefit because of these reasons, and, as discussed earlier,
the
risks are not negligible (10, 11). For example, historically,
physicians have considered major surgery necessary when the
patient
has a mass in the pelvis, because of the fear that the uterus or
ovaries might be harboring an undetected malignancy.


However, high-resolution ultrasound now allows the exact location
and other characteristics of such a mass to be identified, and
allows its size and character to be carefully followed. Uterine
masses in premenopausal women are overwhelmingly benign.
Therefore
the decision on management can often be made based on the woman's
status, presence of bleeding or other symptoms, and information
over
time from modern imaging techniques (10, 11).

Now, conservative surgical approaches which spare the uterus are
growing in use. Benign abnormal uterine bleeding that does not
respond to drug therapy can often be controlled by dilatation and
curettage. An increasing number of practitioners are using
endometrial ablation, the removal or scarring of the endometrium,
to
treat intolerable abnormal bleeding. Simple removal of myomas,
or
myomectomy, either through an incision or using a hysteroscope,
can
be highly effective, and has a low complication rate. Repeat
myomectomy or hysterectomy is required in less than 20 percent of
cases (7).

New approaches, including vaginal hysterectomy with laparoscopic
assistance, and hysterectomy through a laparoscopic incision,
have
not been thoroughly evaluated in terms of outcome. In the past,
hysterectomies performed for benign conditions and for cancer
could
not be performed vaginally. Large fibroids, for example, may
have
made a uterus too large to remove through the vagina. Adhesions
from endometriosis or pelvic inflammatory disease may make
hysterectomy unsafe except from the traditional abdominal
approach.
Exploration of the pelvis and upper abdomen recommended for
patients
with cancer could not be performed through the vagina.

Approaches that use hormone replacement therapy to shrink
fibroids
before surgery, including laparoscopic surgery, have made vaginal
hysterectomy a realistic option for many more women than in the
past. For prolapse, surgery to lift and support the pelvic
organs
usually suffices unless the degree of prolapse is extreme.
Endometriosis is usually treated by local removal of lesions when
medical management fails or produces undesirable side effects
(7).

In obstetrical complications such as severe hemorrhage,
uncontrollable infection, and inversion of the uterus, measures
which spare the uterus may be tried if the patient desires future
fertility. As a last resort, hysterectomy is done when these
fail
and there is a potentially life-threatening emergency (7).

Malignant Disease. For malignant disease, the choice of
management
varies with the type and stage of the cancer. Early, localized
cervical cancer usually may be managed with conservative surgery,
such as removal of part of the cervix, that leaves the body of
the
uterus intact. Intermediate stages of cervical cancer can be
treated with radiotherapy or hysterectomy. Advanced cervical
cancer
is treated with radiotherapy.

Hysterectomy is the accepted treatment for endometrial cancer and
cancer of the uterine muscle (leiomyosarcoma). On occasion,
hormonal agents may be tried in young women with low-grade
endometrial cancer who wish to preserve fertility. Hysterectomy
with removal of both ovaries is generally performed for all
stages
of ovarian cancer. When cancer is confined to one ovary in a
young
woman desiring future fertility, removal of one ovary is an
option
which may be considered.

In summary, modern techniques for non-invasive monitoring of
benign
disease, as well as availability of medical and conservative
surgical treatments, have contributed to the decline in
hysterectomy
rates. Physicians are developing greater confidence that
treatment
which spares the uterus can be safe for the patient. New
developments and wider access to these techniques and treatments
will continue to make alternative strategies even more reliable
and
attractive.

NIH-Supported Activities Relating to Conditions Which Can Lead to
Hysterectomy, and Treatment Alternatives

NIH has been increasingly involved in supporting research and
related activities on diseases and disorders for which
hysterectomies are being done, and on developing alternatives to
hysterectomy. I would like to detail some of these initiatives
and
studies being conducted or supported by various NIH components.

National Cancer Institute (NCI : Research by the NCI-funded
Multi-
institutional Gynecologic Oncology Group is examining the safety
of
estrogen replacement therapy in women with endometrial cancer who
have been treated with hysterectomy and removal of both ovaries.
Retrospective data suggests that estrogen replacement may be safe
for these women. This summer, NCI's Clinical Oncology Program
will
expand the Surgery Branch to include a new gynecologic section
evaluating treatment of gynecological malignancies.

National Institute on Aging (NIA) The NIA is stimulating an
expanded
research focus on the menopause and the role of age-related
changes
in the female reproductive tract in the development of
gynecologic
disorders. A major research conference on menopause recently
sponsored by NIA in conjunction with ORWH and NCNR helped
formulate
recommendations for future NIA research strategies. Topics
covered
a wide range of biomedical and behavioral areas, including
ovarian
biology, cardiovascular health, changes in bone, and
genitourinary
function, and the impact of this life event on minority women.
The
discussion included, for example, ongoing research on effects of
hormone replacement therapy on urinary incontinence, an important
concern for women undergoing either surgical or natural
menopause.

NIA will soon issue a Request for Applications (RFA) in
collaboration with ORWH calling for a comprehensive,
multidisciplinary research effort on the natural history of the
menopause and the role of the perimenopausal transition on
women's
aging and subsequent susceptibility to disease. The initial
phase
of this effort will establish cohorts of premenopausal women, and
will include minority women to redress the previous neglect of
determining ethnic differences in menopause research. The
research
effort will also focus on the postmenopausal ovary and the
dynamics
of hormone replacement therapy and therapeutic alternatives,
contributing important knowledge to the debate on oophorectomy.

NIA has already begun a perimenopausal study of African-American
and
Caucasian women in its intramural research program, as part of
the
Baltimore Longitudinal Study of Aging. NIA is also planning a
major
initiative to explore the impact of age-related changes in the
female reproductive tract on development of gynecologic
disorders,
including myoma and other causes of abnormal bleeding, that can
lead
to hysterectomies in midlife. This solicitation seeks new
strategies to reduce the burden and the high rate of hysterectomy
stemming from disorders or conditions such as myoma and aberrant
gonadotrophin and/or ovarian hormone dynamics as women progress
from
pre- to postreproductive status.

National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS): Longitudinal, prospective clinical studies
funded
by NIAMS are investigating the specific dose and formulation of
estrogen that is most effective in estrogen-deficient women and
the
assessment technologies necessary to follow carefully the
clinical
course of bone health in these women who may be at increased risk
of
fracture. Several studies are directed to the measurement of
bone
quality and quantity using dual energy X-ray absorptiometry,
computed tomography, magnetic resonance and ultrasound. In
addition, biochemical markers of bone remodeling, found in blood
and
urine, may in the future prove to be extremely useful in the
assessment of treatment effectiveness as well as in the
prediction
of risk. The development of biomarkers for osteoporosis was the
subject of a Workshop held by NIAMS in December 1991 and will be
a
major thrust in the NIAMS BONES (Basic Osteoporosis New
Experimental
Strategies) Initiative to be launched in 1993 and implemented in
1994.

National Institute of Child Health and Human Development
(NICHD): Two workshops were held in 1992 on conditions which
can result in hysterectomy--endometriosis, abnormal uterine
bleeding, and myoma. The NICHD and ORWH cosponsored the second
workshop. An explicit emphasis of these workshops was the desire
of
NIH to stimulate research leading to new diagnostic and
therapeutic
advances that would reduce the number of hysterectomies done for
these conditions.

The NICHD and ORWH, with guidance from the workshop participants,
and in response to a direction from the 102nd Congress, jointly
issued a request for applications on endometriosis and myoma,
which
resulted in the award of six new research grants in September,
1992.

In addition, the NICHD currently supports four ongoing clinical
projects on endometriosis. The four ongoing grants include two
projects on the interactions between endometriosis and immune
cells,
and two involving antibodies against endometriosis or proteins
made
by endometriosis cells that could be used as diagnostic markers.
One grant in each of these two areas was co-funded by ORWH.

Some other projects have been the research of three groups
working
with animal models of endometriosis, and an animal study of post-
surgical adhesions (scarring), a common complication of
hysterectomy. Recent clinical investigations have included a
preliminary study of antiprogestin therapy for myomas, and a
study
of prevention of bone loss by ovarian hormones in women with
myomas
treated with GnRH analog.

NICHD-supported research tells us that the uterus has functions
other than as a site for fetal growth. Little is known about the
impact of these functions elsewhere in the body. Removal of the
uterus may thus have unsuspected consequences beyond loss of
fertility. Therefore, it is important to know what the normal
endocrine and metabolic functions of the uterus are. Seven
projects
are addressing this area.

Three investigations are components of a large program project
grant
devoted to the production, metabolism, and regulation of hormones
in
the uterus. Specifically, they involve metabolism of steroid
hormones, regulation of the receptor which allows the uterus to
respond to steroids, and regulation and production of another
class
of hormone, the prostaglandins. Two grants support studies on
interaction between steroids and proteins known as growth factors
in
regulating the growth of endometrial cells. One study looks at
how
prostaglandins act on their target tissues, including mediating
effects of estrogen on the uterus. A young physician scientist
is
directing her investigations at a molecule involved in the immune
response which is especially abundant in endometriosis tissue.

Other projects currently underway include a novel drug delivery
system that could be used for GnRH analogs or other drugs used in
benign disease such as endometriosis or myoma; and a Small
Business
Innovative Research (SBIR) pilot project on an instrument to
quantify changes in uterine physiology in patients with pelvic
pain.

NIDDK: The NIDDK supports studies on irritable bowel syndrome
(IBS),
a very common bowel disorder associated with abdominal pain and
altered bowel habits. Approximately 67 percent of the people who
have symptoms of IBS are women, and approximately 85 percent of
those who seek treatment for this disorder are women. Women with
IBS frequently consult gynecologists, and are three times as
likely
as women without IBS to receive a hysterectomy. Hysterectomy
usually does not relieve their pain, and, may, as a side effect,
predisposes the woman to urinary incontinence. Preliminary
studies
indicate that women have lower thresholds for pain due to
distension
of the colon. Current research is evaluating some of the
physiologic responses to colonic distention and the role of
abdominal pain in reference to menses.

National Heart, Lung, and Blood Institute (NHLBI): The
risk/benefit
picture for hormone replacement therapy is a critical issue for
women facing a decision about hysterectomy with or without
removal
of one or both ovaries. Several NIH Institutes, led by NHLBI, *2
support the Postmenopausal Estrogen/Progestin Intervention (PEPI)
Trial of hormone replacement therapy. The goal of this trial is
to
examine the effects of various hormone replacement strategies on
cardiovascular risk factors, cancer, and osteoporosis.

*2 The NIH institutes participating in the PEPI Trial include,
in
addition to NHLBI: National Institute of Child Health and
Human
Development; National Institute of Diabetes, Digestive, and
Kidney Disease; National Institute of Arthritis,
Musculoskeletal, and Skin Diseases; and National Institute
on
Aging.

Another NHLBI clinical investigation on cardiovascular risk
factors
includes a study of effects of intensive dietary intervention
levels
of HDL and LDL cholesterol, weight gain at the time of menopause,
age at menopause, percent of women using hormone replacement
therapy, or having a hysterectomy.

Several ongoing observational studies are collecting information
on
the use of estrogen and estrogen plus progestin and their
association with lipid levels, coagulation factors, and clinical
events (8).

National Institute for Environmental Health Sciences (NIEHS):
NIEHS
conducts and supports research into environmental hazards that
may
be related to diseases and conditions that are often treated
surgically by hysterectomy. NIEHS studies of substances in the
environment that are estrogens or that act biologically as
estrogens
suggest that these substances may be casually related to cancers
of
the uterus or uterine fibroids. Both of these health conditions
may
be treated by hysterectomy. In addition, NIEHS studies of DES
and
its effect on the children of women given this drug are also
relevant. The goal of this environmental health sciences research
is
to identify and prevent the kinds of environmental exposures that
lead to diseases and conditions of the female reproductive system
and to prevent unnecessary surgical interventions.

National Institute of Mental Health (NIMH): NIMH has an extensive
extramural research program focusing on women's mental health
across
the reproductive cycle. The intramural program of the NIMH has
recently established a women's mental health research center. Of
particular interest is mood changes during the perimenopausal
period, and their relationship to biological changes. The
dramatic biological consequences of hysterectomy, and their
potential effects on mood, are obviously relevant and of great
interest to these programs. In addition, NIMH has a national
education program on Depression Awareness, Recognition and
Treatment, that reaches women and the clinicians who treat them.

National Center for Nursing Research (NCNR): An organization that
is
poised and ready to make a meaningful contribution to our
knowledge
about the behavioral aspects of hysterectomy is the National
Center
for Nursing Research, soon to be NIH's newest institute. The
nursing research community is well positioned to study such
issues
as promoting more rapid healing and recovery following surgery;
describing, analyzing, and ameliorating post-surgical symptoms;
studying symptom management through such therapies as diet and
exercise alone or in combination with hormone replacement
therapy;
and helping women make informed decisions about elective surgery
and
postoperative therapy.

The NCNR is already quite active in this type of research.
Scientific studies address how to manage the well woman's typical
symptoms during menopause, which can also help promote
understanding
of what goes wrong when a woman's symptoms are abnormal. The
goals
are to distinguish and treat, or ameliorate, the normal or
abnormal
symptoms that occur during a woman's middle years. NCNR
supported
NIH's first Center for Women's Health Research, located in
Seattle,
Washington. That Center focuses on such typical mid-life
symptoms
as sleep disruption and gastrointestinal disturbance, as well as
how
women respond to stress.

NCNR has recently funded a study on transitional care. The study
involved releasing women who had hysterectomies early from the
hospital, and subsequently providing them with home follow-up
care
from clinical nurse specialists. These women evidenced improved
health outcomes and expressed greater satisfaction with their
care.
There was also a cost savings of 6 percent which, given the
number
of hysterectomies performed in this country, could be substantial
if
the study findings were to be replicated nationwide.

The NCNR will soon issue a Request for Applications aimed at
studying issues associated with hysterectomy in premenopausal
women.
The request will include studies concerning women's decision
making,
transitional care, post-surgical recovery, symptom management,
and
the long-term implications of the operation.

National Center for Research Resources (NCRR): NCRR supports a
nationwide network of General Clinical Research Centers (GCRCs).
These provide a clinical setting in which investigators with
other
sources of research funding conduct their studies. Current
studies
include a number of basic, clinical and epidemiologic
investigations
into diseases and disorders that lead to hysterectomy, including
myoma, endometriosis, and endometrial and cervical cancers.
Examples of recent projects under way in GCRCs include the
following: Treatment of endometriosis and myoma with
antiprogestin;
long-term treatment of myoma with GnRH analog; treatment of
endometriosis with GnRH analog delivered by nasal spray;
recurrence
rates for myoma following myomectomy; outcome after endoscopic
management of endometriosis; and basic studies of the role of
hormones in the development of endometrial cancer. The NCRR also
supports animal model research, including studies of myoma
response
to hormones and GnRH analogs in primates, and development of a
transgenic animal to study the link between papilloma virus
infection and cervical cancer.

Office of Research on Women's Health (ORWH): The Office
coordinates
the development of an overall NIH women's health agenda and funds
research studies through other NIH components. Examples of such
collaborative efforts range across the biomedical research
spectrum
and include: an animal model testing transformation of normal
ovarian cells to cancerous cells (NCI); testing a model for the
hospital to home transition for women needing that special
attention
required by a patient newly arrived at home (NCNR); a study in
low-
income African American women examining their perceptions and
knowledge of menopause, interest in hormone replacement therapy,
and
health-seeking behaviors (NCNR); and a study of reproductive
failure
as a result of endometriosis (NICHD). Of the 95 awards made by
ORWH
in 1992, 19 (20 percent) related directly to the problems or
issues
faced by women as a result of menopause including surgery.

The Women's Health Initiative (WHI): The largest women's health
research effort ever undertaken, the WHI is a prevention study
to
examine the major causes of death, disability, and frailty --
heart
disease and stroke, cancers (particularly breast and colorectal),
and osteoporosis -- in postmenopausal women (ages 50 through 79
years) of all races and socioeconomic strata. The study will
ultimately involve about 160,000 women. It will examine, through
clinical trials and observational studies, the effect of a
low-fat
diet in preventing breast and colorectal cancer and heart
disease;
the benefits and risks of hormone replacement therapy in
preventing
cardiovascular disease and osteoporotic fractures; and the
effects
of calcium and vitamin D supplements in preventing osteoporotic
fractures and colorectal cancer. The WHI will also study the
effect
of ERT on endometrial cancer.

About 30 percent of the women to be recruited into the clinical
trial are expected to have had an hysterectomy. Of particular
interest are the benefits of estrogen replacement therapy in
reducing the risks for cardiovascular diseases and osteoporosis
in
these women. The randomized clinical trial will also examine
psychosocial and quality of life issues in women on hormone
replacement therapy. For example, cognitive functioning and
various
behavioral measures related to lifestyle events will be studied
with
the goal of assisting women to adopt healthful behaviors that
will
reduce their risk of disease and maximize their health. These
guidelines will also enable health care professionals to assist
and
support their patients.

Research Needs Addressing Alternatives to Hysterectomy

While we have begun to explore the use of new medical therapies,
much more data are needed on their use alone, or in combination
with
surgery that spares the uterus. Studies are also needed on the
effectiveness of conservative surgery with respect to both relief
of
symptoms and likelihood of repeat or more extensive surgery.

For benign disease such as endometriosis, myoma, and pelvic pain,
there is a need for longer-term trials (greater than six months
duration) of medical treatments, especially protocols which use
lower doses, and, alternatively or in combination, include
steroid
replacement to prevent bone density loss and adverse lipid
changes.

While we have some knowledge about medical and surgical treatment
for benign gynecologic disease, we have little information about
less conventional interventions. These modalities could be
effective alone or enhance the utility of medical management,
especially for such conditions as chronic pelvic pain.

As the population of the United States continues to age, the
impact
of aging in development of conditions leading to hysterectomy
takes
on added importance. We do not know if there are functions other
than estrogen production of the endometrial tissue or the ovaries
that continue to be important in postmenopausal health. For
example, it is not well understood whether removal of the
postmenopausal ovary plays a role in osteoporosis. Removal of
the
premenopausal ovary is known to be a major factor in developing
osteoporosis.

Research efforts might be directed at developing combinations of
ovarian hormones and other agents as a potential treatment for
endometrial cancer. Younger women with endometrial cancer may be
treated effectively with these combined new agents, with
hysterectomy being reserved for those with persistent disease.

Because the risks of hormonal replacement therapy are unclear in
patients with a history of ovarian cancer, many clinicians do not
prescribe it for these women. The safety of replacement therapy
needs to be tested in women with a history of ovarian cancer or
ovarian tumors of low malignant potential.

In women for whom hysterectomy is unavoidable, more information
is
needed on the long term biomedical and behavioral consequences of
hysterectomy alone, with removal of the ovaries, and with or
without
hormone replacement therapy. The safety of estrogen replacement
therapy in women with a history of ovarian cancer or ovarian
tumors
of low malignant potential still needs to be determined.

There may be differences in the long-term consequences of
hysterectomy, with or without removal of one or both ovaries, for
members of different racial, ethnic, and socioeconomic groups.
These should be sought as necessary guidance for management
decisions regarding treatment and followup.

Both the public and health care professionals need more
information
on what can be done to minimize, eliminate, or manage the
biomedical
and behavioral consequences of hysterectomy. A wide range of
options must be pursued.

Research is needed on the extent to which the diseases and
conditions leading to hysterectomy are preventable. This would
primarily include factors that influence the development and
growth
of endometriosis, myomas, endometrial hyperplasia, and
gynecological
cancer; and causes of pelvic relaxation.

Strategies Addressing these Needs

The National Institutes of Health has a portfolio of research on
issues surrounding the prevention of hysterectomy as well as
those
interventions which preserve quality of health and life should
hysterectomy become necessary. Yet, further efforts are clearly
required.

The Office of Research on Women's Health (ORWH), the NIH office
whose mandate is to identify and foster a trans-NIH research
agenda
on women's health across the life span of women, has defined
areas
for action in a recent report: The National Institutes of Health:
Opportunities for Research on Women's Health (12). This
document, created from a 1991 public hearing and scientific
workshop, delineates gaps in knowledge in women's health in
specific
age categories and cross-cutting areas of science.
Recommendations for addressing biomedical and behavioral research
issues surrounding hysterectomy, particularly those which
emanated
from the working groups on the ages of the life span, provide
valuable guidance.

The ORWH Workshop Working Group on Young Adulthood to
Perimenopausal
Years (15-44 years of age) recommended that researchers pursue
several parallel lines of inquiry. Those recommendations
included:


ù What can be done to prevent hysterectomy, infertility, and
early fetal loss if a woman suffers from endometriosis or
myomata?

ù How can fertility can be enhanced? How can the potential for
childbearing be preserved in premenopausal women with benign
diseases which were frequently treated in the past by
hysterectomy?

ù What are recommended treatments for women who suffer from
chronic pelvic pain?

ù What methods should be implemented during this life segment
for
preventing lung, breast, colorectal, uterine, and ovarian cancers
in
later years?

The ORWH Workshop Working Group on Perimenopausal to Mature Years
(45-64 years of age) recommended additional studies on a variety
of
different research issues. Such recommendations included:

. What are the effects of hormone replacement therapy on heart
disease; breast, uterine, and other cancers; osteoporosis; and
mental health?

. What are the changes, both psychological and physiological,
that
occur in a woman as she approaches and enters into menopause?

ù What are the effects of early menopause on the health of a
woman?

ù What are the psychological and physiological effects on
women
as they age?

The ORWH Workshop Working Group on Mature Years (65 years and
older)
provided similar recommendations.

ù What are the long-term psychological and physiological
effects
of menopause?

ù What are the ways that health care workers can be made aware
of
the special problems faced by women over age 65?

ù What measures can lead to an improvement in women's
self-esteem
during this part of the life span?

ù Can the increased prevalence of depression among women
having
had an hysterectomy (either pre or post menopausal) be prevented
or
reversed?


With an estimated 35 percent of women in this country over the
age
of 60 having had a hysterectomy, and a substantial number of
younger
women at risk for hysterectomy, finding answers to these and
related
research questions, becomes critically important.


As the focal point for action on women's health across the NIH,
our
goal is to make women's health issues an integral part of
scientific
inquiry at NIH and throughout the scientific community. Drawing
together the different NIH initiatives relating to hysterectomy
has
provided yet another important opportunity to examine gaps in
knowledge and to stimulate change to enhance women's health.
Your
interest and support has encouraged us to redouble our efforts in
this important area of women's health.

Conclusions

While hysterectomy rates are declining, 35 percent of American
women
will have had an hysterectomy by the time they reach the age of
60.
Approximately 300 deaths per year occur after hysterectomy for
benign disease. Some medical therapies are available, but each
has
potential problems for many women. More information is needed on
non-surgical interventions and other treatments. The risks and
benefits of surgery that spares the uterus also need further
study.

The NIH is committed to focusing its efforts on this significant
public health issue. In particular, we are strengthening our
activities to expand the knowledge base that will lead to either
the
prevention of those conditions that today frequently result in
hysterectomy, or the development of an array of improved
alternative
therapies for these disorders. NIH recognizes that prevention
may
be an important key to avoiding unnecessary hysterectomies.

We are grateful to you, Senator Mikulski, for providing the
impetus
and leadership to concentrate our attention even more intently on
hysterectomy and alternatives to this procedure, and to spur us
to
increased collaborative efforts.

I shall be pleased to answer any questions you may have.


1 National Center for Health Statistics, Pokras R, Hufnagel
VG.
Hysterectomies in the United States, 1965-1984. Vital and Health
Statistics. Series 13, No. 92. DHHS Publication no. (PHS)
88-1753.
Washington. US Government Printing Off ice (1 988).

2. Personal communication from Mr. Robert Pokras.

3. National Hospital Discharge Survey, National Center for
Health
Statistics, CDC (unpublished data), 1991.

4. Meilahn EN, Matthews KA, Egeland G, Kelsy SF.
Characteristics
of women with hysterectomy. Maturitas 11:319-329 (1989).

5. Kjerulff, K, Langenberg P, Guzinski, G. The Socioeconomic
correlates of hysterectomies in the United States. American
Journal
of Public Health 83:106-108 (1993).

6. Pokras, R. Hysterectomy: Past, Present, and Future.
Statistical Bulletin, 70:12-21 (1989).

7. Carlson KJ, Nichols DH, Schiff 1. Indications for
hysterectomy.
New England Journal of Medicine, 328:856-60 (1993).

8. Nabulsi, A, et al. Association of Hormone Replacement
Therapy
with Various Cardiovascular Risk Factors in Postmenopausal Women.
New England Journal of Medicine, 328:1069-1075 (1993).

9. Speroff T, Dawson NV, Speroff L, Haber RJ A risk-benefit
analysis of elective bilateral oophorectomy: effect of changes in
compliance with estrogen therapy on outcome. American Journal of
Obstetrics and Gynecology 164:165-74 (1991)

10. Friedman AJ, Haas ST. Should uterine size be an indication
for
surgical intervention in women with myomas? American Journal of
Obstetrics and Gynecology 168:751-55 (1993).

11. Reiter RC, Wagner PL, Gambone JC. Routine hysterectomy for
large asymptomatic uterine leiomyomata: a reappraisal.
Obstetrics
and Gynecology 79:481-4 (1992)

12. National Institutes of Health. Opportunities for Research
on
Women's Health. Bethesda: National Institutes of Health;
1992.

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