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Elective oophorectomy or ovarian conservation at the time of hysterectomy

Authors: Susan D Reed, MD, MPH, Barbara Goff, MD

Section Editor: Howard T Sharp, MD
Deputy Editor: Sandy J Falk, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2018. | This topic last updated: Sep 26, 2016.

INTRODUCTION — Hysterectomy (surgical removal of the uterus) is the second most common major surgical procedure (cesarean section is the most common) performed among United States women [1]. Women undergo
oophorectomy at the time of hysterectomy less frequently than in the past [2]. A 2005 United States nationwide study reported that unilateral or bilateral oophorectomy was performed in 68 percent of women at the time of
abdominal hysterectomy, 60 percent at laparoscopic hysterectomy, and 26 percent at vaginal hysterectomy [3]. A study from 2013 to 2014 showed that 44 percent of women younger than 51 years had oophorectomy at the
time of hysterectomy for benign disease (outcomes were: normal ovaries 23 percent; ovarian cancer 0.2 percent; and benign pathology 21 percent).

Historically, it had been common practice to counsel women in their mid-40s or older who were planning hysterectomy for benign indications to undergo concomitant bilateral salpingo-oophorectomy [4]. The rationale for this
approach was that oophorectomy greatly decreases the risk of ovarian cancer and the need for future ovarian surgery, and that there is little disadvantage of ovarian preservation, since women in this age range are close to
or beyond menopause. This approach also assumed nearly universal treatment with postmenopausal hormone therapy.

A growing understanding of the potential long-term health risks of elective oophorectomy and potential advantages of elective salpingectomy in premenopausal women has changed clinical practice [5,6]. In the setting of
benign disease, the decision to retain or remove tubes and ovaries should be based upon the long-term health effects. The pendulum has swung toward ovarian conservation in women under age 51 [4,7].

For women with a gynecologic malignancy, there are often clear indications for salpingo-oophorectomy. For those at high genetic risk of ovarian cancer, risk-reducing salpingo-oophorectomy or salpingectomy may be
indicated.

An evidence-based approach to management of the tubes and ovaries at the time of hysterectomy for benign disease will be reviewed here. Techniques for salpingectomy and oophorectomy, risk-reducing salpingectomy
and oophorectomy for women with a hereditary ovarian cancer syndrome, and general principles of menopause are discussed separately. (See "Oophorectomy and ovarian cystectomy" and "Risk-reducing bilateral salpingo-
oophorectomy in women at high risk of epithelial ovarian and fallopian tubal cancer" and "Clinical manifestations and diagnosis of menopause".)

TERMINOLOGY

● Elective salpingo-oophorectomy – Removal of the ovaries and fallopian tubes in a woman who has no known indication for this procedure (eg, ovarian pathology, hereditary ovarian cancer syndrome). Ovaries and
tubes are typically removed, rather than the ovaries alone.

● Risk-reducing salpingo-oophorectomy – Removal of the ovaries and fallopian tubes in a woman with a hereditary ovarian cancer syndrome. Risk reduction requires removal of the tubes as well as the ovaries
because some malignancies currently categorized as ovarian cancers may arise in the tubal epithelium. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal
cancer".)

● Risk-reducing salpingectomy – Removal of just the fallopian tubes in a woman with a general population risk of ovarian cancer syndrome. Risk reduction removes the tubes because many malignancies currently
categorized as ovarian cancers may arise in the tubal epithelium.

The term prophylactic salpingo-oophorectomy has been used inconsistently, and so will not be used in this review, except when it was the term used in a particular study. It has been used variously to refer to salpingo-
oophorectomy for the prevention of ovarian cancer in either women at an average risk or those with a hereditary ovarian cancer syndrome [8,9].

SURGICAL EFFECTS ON OVARIAN FUNCTION

Surgical menopause — The ovary is an endocrine organ, with widespread physiologic effects during the postmenopausal, as well as the reproductive, years.

In women who haven’t previously undergone natural menopause, bilateral oophorectomy or remaining oophorectomy (removal of an ovary in a woman who has previously undergone unilateral oophorectomy) results in
surgical menopause. The rapid change in the reproductive hormonal milieu and abrupt symptom onset that occurs in surgical menopause contrasts with the typical gradual waxing and waning in the hormonal profile and
concomitant menopausal symptoms that occur in natural menopause.

Surgical menopause results in an abrupt drop in estrogen levels, an abrupt rise in follicle stimulating hormone (FSH) level, and the complete cessation of ovarian hormone production, including androgens, estradiol, and
progesterone [10-13].

By contrast, the transition into natural menopause is characterized by variable estradiol and FSH levels, in association with unpredictable ovulatory and anovulatory cycles. The variability in hormone levels is most dramatic
over a period of four years, and typically continues over an interval of up to 10 years [14,15]. Ultimately, estrogen levels remain low and FSH levels high, but there is no specific hormone level profile that unequivocally
characterizes the onset of natural menopause. Intact postmenopausal ovaries continue to be hormonally active for many years beyond menopause, producing androgens including testosterone, androstenedione, and
dehydroepiandrosterone (DHEA), as well as very small amounts of estradiol and estrone [16]. Although estrogen secretion by the postmenopausal ovary eventually ceases, ovarian secretion of small amounts of testosterone
and the androgen precursor, DHEA, may continue into the eighth decade of life [12,16].

Extraovarian sources of sex steroids throughout life include the adrenal glands and widespread target tissues, including fat, where aromatization of androgens into estrogen occurs. The extent to which extraovarian sex
steroid hormone synthesis differs between women who have experienced natural versus surgical menopause has been debated [12,13], but it appears that total androgen levels remain lower after surgical menopause than
after natural menopause [12].

Early menopause following hysterectomy — Hysterectomy appears to alter ovarian function over the long-term, even if the ovaries are conserved. This effect is incompletely understood, but is possibly due to impairment
of the ovarian blood supply or other yet unknown mechanisms [17-20]. Observational studies have found that women who undergo hysterectomy develop menopausal symptoms and menopausal hormone profiles earlier
than controls that did not have a hysterectomy. As an example, a prospective cohort study found that menopause (defined as follicle stimulating hormone ≥40 IU/L) occurred 3.7 years earlier in premenopausal women who
had a hysterectomy (both ovaries retained) compared with those who did not have a hysterectomy [20]. And, among all women who underwent hysterectomy, those who had only one ovary conserved reached menopause
4.4 years earlier than those who had both ovaries conserved.

INDICATIONS FOR OOPHORECTOMY — Women who undergo hysterectomy for benign indications may also have an indication for concurrent oophorectomy. Oophorectomy in this context is not elective. However, even in
this circumstance, the risk-to-benefit balance of bilateral oophorectomy should be considered.

Ovarian pathology is the usual indication for oophorectomy (eg, ovarian neoplasms). These indications are reviewed separately. (See "Oophorectomy and ovarian cystectomy", section on 'Oophorectomy versus
cystectomy'.)

Some women with extraovarian pathology may also benefit from oophorectomy, including:

● Endometriosis – The risk of reoperation for endometriosis-related concerns appears to be lower if the ovaries are removed at the time of hysterectomy [21]. (See "Endometriosis: Treatment of pelvic pain", section on
'Surgical treatment options'.)

● Tubo-ovarian abscess – In women requiring surgical management of tubo-ovarian abscess, the risk of reoperation is higher if one or both ovaries are conserved [22]. (See "Management and complications of tubo-
ovarian abscess", section on 'Surgery'.)

● Pelvic adhesions/pelvic pain – The incidence of residual ovary syndrome, characterized by post-hysterectomy pelvic pain, is 0.9 to 3.4 percent [23]. Subsequent oophorectomy may be required to manage such
symptoms. Preoperative pelvic pain and adhesions are risk factors for this syndrome. Thus, hysterectomy with bilateral salpingo-oophorectomy has been a common approach for such patients [24].

STUDIES REGARDING ELECTIVE OOPHORECTOMY — The highest quality data regarding long-term health outcomes of elective oophorectomy compared with ovarian conservation at time of surgery are from two large
prospective studies and a single retrospective cohort study discussed below; no randomized trial has investigated this issue:

● The Nurses’ Health Study was a prospective cohort study that included 29,380 women who had a hysterectomy for benign disease [25,26]. The average age at time of surgery was approximately 43 to 47 years and the
average age at enrollment was 51 years; 94 percent were white; women were followed for 28 years.

● The Women’s Health Initiative Observational Study was a prospective study that included 25,448 women who had a hysterectomy for benign disease [27]. Women in this study were initially invited to participate in the
Women’s Health Initiative randomized trial that evaluated postmenopausal hormone therapy, but were either found ineligible or declined to participate in the trial. The majority of women were 49 years or younger at the
time of hysterectomy and the average age at enrollment was 63 years; 82 percent were white; women were followed for an average of only eight years.

● The Mayo Clinic Cohort Study of Oophorectomy and Aging was a retrospective population-based cohort study of 2365 women in Olmstead County, Minnesota who underwent unilateral or bilateral oophorectomy for
benign disease; almost all women were white [28]. For some analyses, women from the cohort were compared with controls who had not had an oophorectomy and were identified via random digit telephone dialing
[29]. The median age at time of surgery was 44 years among premenopausal women who had a bilateral oophorectomy and 62 years among postmenopausal women. Women who had a bilateral oophorectomy were
followed for an average of 25 years; 95 percent had the oophorectomy at the time of hysterectomy. Although this study was retrospective, it includes prospective data from centralized medical records regarding the

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surgical, pharmacy, and outcome data for all participants. Thus, recall bias was limited and there was access to long-term follow-up data.

Findings from these studies, as well as from other relevant studies, are reviewed in the sections that follow. Data from the Women’s Health Initiative conflict with data from the Nurses’ Health Study and the Mayo Clinic
Cohort Study regarding many outcomes, including risk of all-cause mortality, cardiovascular disease and osteoporotic fractures. We regard the Nurses’ Health Study as having the best available data, based upon several
methodologic limitations of the Women’s Health Initiative Observational Study. Both the Nurses’ Health Study and the Mayo Clinic Cohort Study had long follow-up periods (28 to 30 years), adequate to assess outcomes that
are more common for women over age 60 years: cardiovascular disease and stroke, dementia, osteoporosis, breast cancer, ovarian cancer and all-cause mortality, and shorter gaps between oophorectomy and enrollment.
In contrast, women in the Women’s Health Initiative were followed for only a mean of 8 years with an average gap of 14 years from oophorectomy to enrollment. The average age at enrollment in the Women’s Health
Initiative Observational Study was 63 years. Thus, women who had outcomes of interest (cardiovascular disease and stroke, dementia, osteoporosis, breast cancer, ovarian cancer and all-cause mortality) that occurred
during the interval from hysterectomy to enrollment were not included, introducing a significant survivor bias to the analysis. Finally, the Women’s Health Initiative Observational Study reported that bilateral salpingo-
oophorectomy did not have significant adverse effects on all-cause mortality, coronary heart disease, hip fracture, or cancer, but the study has insufficient statistical power to detect differences for these outcomes.

BENEFITS OF ELECTIVE OOPHORECTOMY

Ovarian cancer risk reduction — Bilateral salpingo-oophorectomy (BSO) reduces, but does not eliminate, the risk of developing ovarian cancer. Ovarian-like cancers of the peritoneum, known as peritoneal cancer, may
develop after oophorectomy. Oophorectomy performed for ovarian cancer risk reduction should include removal of the fallopian tubes since occult primary fallopian tubal cancers have been reported in women undergoing
risk-reducing BSO. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Incidental operative finding'.)

BSO is an important risk reduction strategy for women who are at high risk of ovarian cancer. The lifetime risk of ovarian cancer in the general population is 1.4 percent compared with 13 to 46 percent in women with BRCA1
or BRCA2 gene mutations (table 1) and 3 to 14 percent in those with Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome) (figure 1) [30]. Salpingo-oophorectomy in these women is considered risk-
reducing and not elective. (See "Endometrial and ovarian cancer screening and prevention in women with Lynch syndrome (hereditary nonpolyposis colorectal cancer)" and "Risk-reducing bilateral salpingo-oophorectomy in
women at high risk of epithelial ovarian and fallopian tubal cancer" and "Overview of hereditary breast and ovarian cancer syndromes".)

The degree of ovarian cancer risk reduction from hysterectomy with BSO in the general population was illustrated in prospective data from the Nurses' Health Study (see 'Studies regarding elective oophorectomy' above)
[26]. The analyses were adjusted for family history of ovarian cancer and duration of oral contraceptive use. Women who underwent oophorectomy had significant reductions in ovarian cancer mortality compared with
women who conserved their ovaries (hazard ratio [HR] 0.06, 95% CI 0.02–0.17).

Similar results were reported by the Women’s Health Initiative Observational study, another large prospective cohort study, in which the number needed to treat to avoid one case of ovarian cancer was 323 [27].

The decision regarding BSO at time of hysterectomy is more difficult for women who have some risk factors for ovarian cancer (table 2), but who do not have, or have not been tested for, a hereditary ovarian cancer
syndrome. Women for whom a familial cancer syndrome is suspected should be offered genetic counseling and testing (table 3 and table 4). Counseling of patients who have some of the known risk factors for ovarian
cancer, but who do not meet criteria for a high risk of ovarian cancer, must be individualized and should include review of all advantages and disadvantages of the procedure. This is an area of uncertainty in which further
research is needed to guide the practice. (See "Management of patients at high risk for breast and ovarian cancer".)

Alternatives to BSO for ovarian cancer risk reduction — Surgical procedures other than BSO may reduce the risk of ovarian cancer, without resulting in surgical menopause.

Procedures that interrupt or remove the fallopian tubes appear to reduce the risk of ovarian cancer, but not to the same extent as BSO. Hysterectomy alone was associated with a 34 percent reduction in the risk of ovarian
cancer in a meta-analysis of 12 case-control studies [31]. Tubal ligation was found to be associated with a 34 percent reduction in ovarian cancer risk in meta-analysis of case-control studies [32].

Bilateral salpingectomy alone without oophorectomy has also been proposed [5,6,33,34]. The Society of Gynecology Oncology (SGO) suggests that for women at average risk of ovarian cancer, risk-reducing salpingectomy
should also be discussed and considered with patients at the time of abdominal or pelvic surgery, hysterectomy, or in lieu of tubal ligation [6] (see "Opportunistic salpingectomy for ovarian, fallopian tubal, and peritoneal
carcinoma risk reduction"). Potential mechanisms for the protective effect of these procedures include: (1) eliminating lesions that may have originated in the fallopian tubes; (2) limiting the potential for upward migration of
carcinogens through the vagina, cervix, and fallopian tubes into the peritoneal cavity; and (3) providing a cancer screening effect [35].

Unilateral oophorectomy has not been proven to reduce the risk of ovarian cancer. Although this observation is counterintuitive, available data have not consistently demonstrated that removing half of the tissue at risk
results in half the risk of ovarian cancer. A multicenter case-control study of 1031 women with ovarian cancer who were compared with women who did not undergo pelvic surgery found no significant decrease in ovarian
cancer risk over a period of seven years in those who underwent unilateral oophorectomy either with hysterectomy (1.4 versus 2.6 percent) or without hysterectomy (1.0 versus 1.6 percent) compared with no pelvic surgery
[36]. In contrast, a case-control study of 129 women with ovarian cancer found a significantly decreased rate of ovarian cancer over a period of 16 years in women who had undergone unilateral oophorectomy (2.9 versus
13.6 percent) [37]. Further study of this issue is needed.

Breast cancer risk reduction — Oophorectomy appears to reduce the risk of breast cancer in women who are 45 years old or younger at time of surgery. The reduced risk of breast cancer is likely due to reduced exposure
to estrogen from the premenopausal ovary. This effect is also seen in women at high risk of breast cancer. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal
cancer", section on 'Breast cancer'.)

The Nurses' Health Study, a large prospective study, found that oophorectomy was associated with a significant reduction in breast cancer incidence only in women who underwent the procedure at age 47.5 years or
younger [26]. (See 'Studies regarding elective oophorectomy' above.)

In contrast, the Women's Health Initiative Observational study found a significant reduction in breast cancer risk ONLY in women who underwent oophorectomy at age <40 and also did not take estrogen therapy; these
findings can be explained by limitations in the study design [27]. (See 'Studies regarding elective oophorectomy' above.)

Avoiding the need for subsequent oophorectomy — Reoperation for ovarian pathology, termed residual ovary syndrome, occurred in 3 to 4 percent of women who retained one or both ovaries after hysterectomy, based
upon two case series performed between 1970 and 1990 [23,38]. The majority of these surgeries were performed within five years of the hysterectomy for the indication of pelvic pain or a pelvic mass. In one series of 2561
hysterectomies, among 73 women with residual ovary syndrome, histologic examination revealed functional cysts in 51 percent, benign neoplasms in 43 percent, and ovarian carcinoma in 12 percent of cases (some patients
had more than one diagnosis) [23]. The other series included 1265 women and found that the frequency of residual ovary syndrome was twice as high in women who had one ovary preserved, rather than both (7.6 versus
3.6 percent) [38]. In addition, residual ovary syndrome was more common in women who underwent hysterectomy at a young age, possibly because of the longer period of post-procedure ovarian function with a greater
opportunity for functional ovarian pathology.

Some data suggest that the reoperation rate is higher in women who undergo abdominal or laparoscopic hysterectomy compared with a vaginal route [39]. The reason for such a difference is uncertain, but it could be that
vaginal hysterectomy is typically not performed when ovarian pathology in one or both ovaries is suspected.

In women who require oophorectomy subsequent to hysterectomy, laparoscopic techniques have reduced the surgical morbidity of such procedures. However, surgical adhesions from prior hysterectomy may make a
laparoscopic approach more difficult. One small study reported that 32 of 35 women with a prior hysterectomy were able to have a successful laparoscopic oophorectomy [24]. Thus, minimally invasive surgery will provide a
solution for most women who develop ovarian pathology following hysterectomy. Therefore, the possible need for subsequent surgery does not appear to justify the deleterious long-term consequences of BSO for most
women undergoing hysterectomy.

RISKS OF ELECTIVE OOPHORECTOMY

Added surgical risk — Operative complications are uncommon in women undergoing elective bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy. The risk of such complications is increased if adhesions or
other intraabdominal pathology are present.

The impact of BSO on surgical morbidity is controversial. This may depend somewhat upon surgical route. For hysterectomy performed via laparotomy or laparoscopy, BSO does not appreciably increase the complexity of
the procedure. In contrast, when BSO is combined with vaginal hysterectomy, the procedure is potentially more difficult. The degree of difficulty depends upon the extent of descensus of the ovaries and the extent to which
the ovaries can be brought into the narrow surgical field. This is consistent with the findings of a study of over two million women in the United States who underwent hysterectomy for benign indications from 1998 to 2006
[40]. There was an increase in complications when BSO was performed in women undergoing vaginal hysterectomy (odds ratio [OR] 1.12; 95% CI 1.08-1.17), but not for those who had an abdominal (OR 0.91; 95% CI
0.89-0.94) or laparoscopic hysterectomy (OR 0.89; 95% CI 0.83-0.94). (See "Abdominal hysterectomy", section on 'Adnexal conservation or removal' and "Vaginal hysterectomy", section on 'Adnexal evaluation and
surgery'.)

In contrast, an increase in morbidity with BSO was found in another study of over nine million women who had a hysterectomy performed between 1979 and 2004 identified via the United States National Hospital Discharge
Survey database. Most were abdominal hysterectomies (84 percent); individual rates of other surgical routes were not given [41]. Although a study population with a predominantly abdominal surgical route is no longer
representative of current practice, findings showed that hysterectomy with oophorectomy compared with hysterectomy alone had significantly increased risks of circulatory/bleeding complications (1.4 versus 1.2 percent; OR
1.34, 95% CI 1.05–1.70), organ injury (1.3 versus 0.9 percent; OR 1.35, 95% CI 1.02–1.79), and gastrointestinal complications (1.7 versus 0.7 percent; OR 1.76, 95% CI 1.31–2.37) [3].

The available data do not take into consideration whether the oophorectomy was elective or indicated. Some indications for oophorectomy may contribute to surgical morbidity (eg, pelvic adhesions, large adnexal mass).
Further study is needed to evaluate whether elective BSO impacts surgical morbidity.

Long-term health risks — Accumulating evidence indicates that surgical removal of the ovaries may have serious long-term health consequences [25-28,42-46]. It appears that risks are greater for women who are younger
at the time of oophorectomy and did not take estrogen therapy [28,42-44,47].

All-cause mortality — The available evidence suggests that bilateral oophorectomy at younger age is associated with increased all-cause mortality, especially among women who do not take estrogen therapy. Questions
remain regarding the potential mechanism of this effect, but evidence is suggestive that hypoestrogenism may be an important factor.

The Nurses’ Health Study found that women who underwent bilateral oophorectomy had a significantly increased risk of death from all causes compared with those who conserved their ovaries (16.8 versus 13.3 percent; HR
1.13, 95% CI 1.06–1.21). (See 'Studies regarding elective oophorectomy' above.) This can also be expressed as one additional death over a period of 24 years for every 24 women who undergo bilateral oophorectomy at
time of hysterectomy.

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The etiology of the increase in all-cause mortality with oophorectomy in the Nurses’ Health Study is unknown, but among women younger than 50 years, the increase in risk following oophorectomy was significantly higher
for those who never used estrogen therapy (HR 1.41, 95% CI 1.04–1.92) than those who had ever used, or were currently, using estrogen therapy (HR 1.05, 95% CI 0.94–1.17) [26]. Among all women, oophorectomy was
associated with a significant increase in death due to lung cancer (HR 1.29, 95% CI 1.04–1.61), and colorectal cancer (HR 1.49, 95% CI 1.02–2.18).

As in the Nurses’ Health Study, younger women in the Mayo Cohort Oophorectomy and Aging Study who underwent prophylactic BSO had an increased all-cause mortality risk (HR 1.67, 95% CI 1.16-2.40) [28].

Elective and indicated oophorectomies were analyzed separately in only one study, the Mayo Cohort Study of Oophorectomy and Aging [28]. (See 'Studies regarding elective oophorectomy' above.) A significant increase in
all-cause mortality compared with referent women without oophorectomy was found only in those in whom the oophorectomy was indicated due to a benign tumor or inflammation. The causes of death were not reported.
The risk of death was significantly increased in women who underwent prophylactic oophorectomy compared with no oophorectomy only in those who were younger than age 45 years and did not use subsequent estrogen
therapy (29 versus 26 percent). The study lacked sufficient statistical power to detect a difference in outcome in other women who underwent prophylactic oophorectomy. Further study of the distinction between indicated
and elective oophorectomies is needed. (See 'Indications for oophorectomy' above.)

In contrast to findings from the Nurses’ Health Study and the Mayo Cohort Study of Oophorectomy and Aging, the Women’s Health Initiative Observational Study found no increase in mortality in women who underwent
hysterectomy with bilateral oophorectomy compared to ovarian conservation, overall (797 versus 791 per 100,000 person-years; HR 0.98, 95% CI 0.87-1.10) or for any age group subset [27]. A discussion of study limitations
can be found above. (See 'Studies regarding elective oophorectomy' above.)

Cardiovascular disease and stroke — The available evidence suggests that BSO at a younger age is associated with an increased risk of cardiovascular disease [26,47,48]. It is uncertain whether an increase in
cardiovascular risk is the result of early menopause, or is associated specifically with surgical menopause. Some data suggest that estrogen therapy may mitigate adverse cardiovascular effects in this patient population
[25,44]. The relationship between postmenopausal hormone therapy and cardiovascular disease is discussed in detail separately. (See "Menopausal hormone therapy and cardiovascular risk".)

The association between cardiovascular disease and oophorectomy is supported by data from a meta-analysis and large observational studies [26,47-49]. Women who undergo bilateral oophorectomy appear to be more
likely than premenopausal women to develop cardiovascular disease, based upon a meta-analysis of 18 studies that found a significantly increased risk of cardiovascular disease in women who underwent bilateral
oophorectomy compared with premenopausal women (RR 2.62, 95% CI, 2.05-3.35) [48]. In contrast, no significant difference was found between natural menopause and premenopause (RR 1.14, 95% CI 0.86-1.51).
Surgical menopause was not directly compared with natural menopause. Early age at oophorectomy had a deleterious effect. The increase in cardiovascular risk was significantly higher in women who underwent bilateral
oophorectomy before age 50 years compared with 50 years or older (RR 4.55, 95% CI 2.56-8.01).

On the other hand, early natural menopause (≤44 years old) has been associated with an increase in the risk of cardiovascular disease in two large epidemiologic studies [50,51]. In one, this effect was limited to current
smokers [50], while the second study only included women who never smoked [51]. (See "Overview of cardiovascular risk factors in women", section on 'Menopause'.)

The Nurses’ Health Study found a significant increase in cardiovascular disease (HR 1.19, 95% CI 1.01–1.39) and an increase in coronary heart disease that was not statistically significant (HR 1.23, 95% CI 1.00–1.52) [26].
Among women younger than 50 years, the increased risk following oophorectomy was significantly higher for those who never used estrogen therapy (HR 1.60. 95% CI 0.68–3.74) than those who had ever, or were currently,
using estrogen therapy (HR 1.00, 95% CI 0.76–1.33).

Similarly, among younger women in the Mayo Cohort Oophorectomy and Aging Study, women who underwent BSO and were not treated with estrogen from the time of BSO through age 45 years had an increased
cardiovascular mortality risk (HR 1.84, 95% CI 1.27-2.68), while those who were treated with estrogen therapy were not found to have a significantly increased risk (HR 0.65, 95% CI 0.30-1.41), although this analysis had
insufficient statistical power [44].

There may not be an increased risk for cardiovascular disease among women who undergo BSO in the menopause transition. The Study of Women's Health Across the Nation, a prospective cohort study of over 3000
premenopausal women from diverse ethnic backgrounds, followed 42- to 52-year-old women for up to 11 years. By 2008, 1769 had become menopausal, 77 had hysterectomy, and 106 had hysterectomy with bilateral
salpingo-oophorectomy. Women were followed annually for changes in risks for cardiovascular disease, 4.7 +/- 2.3 years after the final menstrual period or surgery [52]. No differences between groups were observed in
annual changes in CVD risk factors: lipids, insulin resistance, blood pressure, hemostatic, and inflammatory factors.

The Women's Health Initiative Observational study found no significant association between oophorectomy (study population age at BSO: <40, 22 percent; 40 to 49, 47 percent; ≥50, 31 percent) and coronary heart disease
(380 versus 353 per 100,000 person-years; HR 1.00, 0.85 to 1.18). This could be due to older age at BSO (menopause transition or greater) or methodologic issues that limit confidence in this finding [27]. A discussion of
study limitations can be found above. (See 'Studies regarding elective oophorectomy' above.)

No study found a significant association overall between oophorectomy and stroke.

Cognitive function and neurologic disease — Oophorectomy prior to menopause appears to be associated with an increased risk of cognitive impairment or dementia, as well as parkinsonism. Estrogen therapy may
be neuroprotective in these women. (See "Estrogen and cognitive function", section on 'Timing of exposure' and "Menopausal hormone therapy: Benefits and risks", section on 'Cognitive function and dementia'.)

This was illustrated in the Mayo Clinic Cohort Study of Oophorectomy and Aging [53,54]. Among women who underwent bilateral oophorectomy before menopause compared with those who did not undergo oophorectomy,
a significant increase in the risk of cognitive impairment or dementia was restricted to those who were younger than 48 years old at time of surgery and who did not take estrogen therapy from time of surgery through age 50
years (HR 1.89, 95% CI 1.27–2.83).

Small observational studies have shown a significant decrease in specific cognitive functions after bilateral oophorectomy, including verbal fluency, verbal memory, procedural learning, and some other executive functions
[42,55]. Neurocognitive performance was worse when oophorectomy occurred at younger ages and worse with a greater decline in estradiol levels, but it was better when hormone therapy was initiated after oophorectomy.
The extent to which observed improvements in neurocognitive performance with estrogen therapy might be attributable to improvements in sleep and relief of hot flashes versus direct effects on the brain has been debated
[55].

In the Mayo Clinic Cohort Study of Oophorectomy and Aging, women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with no oophorectomy (2.6
versus 1.2 percent), and the risk increased with younger age at oophorectomy [54,56]. An increase in the risk of Parkinson’s disease was also found, but did not reach statistical significance.

Depression and anxiety — Some data suggest that early bilateral oophorectomy at the time of hysterectomy is associated with an increased risk of developing depression or anxiety [42,57,58].

The Mayo Clinic Cohort Study of Oophorectomy and Aging reported that women who had bilateral oophorectomy compared with those who did not had a significant increase in the onset of symptoms of depression (as
diagnosed by a physician, 11 versus 7 percent) or anxiety (7 versus 3 percent) [42]. The median time from oophorectomy to the onset of symptoms of depression or anxiety was approximately 14 years, but differences in the
rates of occurrence of anxiety and depression were observed within three years following hysterectomy, and persisted throughout more than 30 years of follow-up.

The Study of Women Across the Nation compared risk of depression and anxiety among women who had hysterectomy with ovarian conservation (n = 76) versus women who had hysterectomy with bilateral oophorectomy
(n = 101). For all women, depressive and anxiety symptoms decreased in the years after final menstrual period or surgery [58].

Data from shorter-term studies have been inconsistent regarding the effect of bilateral oophorectomy on psychological well-being [59,60].

Glaucoma — Neuroprotective effects of estrogen on the optic nerve and a decreased risk of glaucoma, the second leading cause of blindness world-wide, have been described [45,46]. (See "Open-angle glaucoma:
Epidemiology, clinical presentation, and diagnosis".)

The Mayo Clinic Cohort Study of Oophorectomy and Aging reported that women who had bilateral oophorectomy before the age of 43 years compared with those who did not have a significant increase in open-angle-
glaucoma (as identified by diagnostic codes and confirmed in a subset chart validation study). The risk (aHR 1.60, 95% CI 1.15-2.23) was not ameliorated in women who took estrogen, although numbers were small [45]. In
the Nurses’ Health Study, glaucoma risk was 50 percent lower in women who underwent menopause at 54 years or older, compared with those under 54 years [46].

Sexual dysfunction — Studies report negative sexual outcomes after oophorectomy in premenopausal women not treated with hormones.

Adverse effects of bilateral oophorectomy can involve several different domains of sexual function, including libido, arousal, and orgasm [57]. In a survey of European women with no known increased risk of cancer, those
who underwent bilateral oophorectomy were twice as likely to have hypoactive sexual desire symptoms compared with women who were premenopausal or had gone through natural menopause [61].

Greater impairment of sexual function may be associated with surgical versus natural menopause since only surgical menopause is associated with an abrupt decrease in androgen output. In a cross-sectional study of over
30,000 women, surgical, but not natural, menopause was associated with orgasm problems and the decrease in arousal was greater in women after surgical menopause [62]. Similarly, in one retrospective study of women
following hysterectomy, women who had bilateral oophorectomy reported significantly decreased sexual satisfaction postoperatively, despite estrogen treatment, compared to women who had their ovaries preserved [59]. On
the other hand, this result was not observed in a subsequent prospective study in which sexuality was unaltered postoperatively in women following hysterectomy with bilateral oophorectomy compared with hysterectomy
only [63]. (See "Sexual dysfunction in women: Epidemiology, risk factors, and evaluation", section on 'Age and menopause'.)

Other studies have found that overall sexual function is unaltered after oophorectomy, or that alterations were explained by preoperative sexual function, indications for surgery, severity of symptoms, and personality traits,
rather than by the oophorectomy itself; however, the majority of women studied were in the menopause transition or were postmenopausal. [4,64-66].

Osteoporosis — Menopause is a known risk factor for osteoporosis. Among women in the Mayo Clinic Cohort of Oophorectomy and Aging who were postmenopausal at the time of surgery, there was a significant
increase in the risk of any osteoporotic fracture (moderate trauma fractures of the hip, spine, or distal forearm) as compared to expected rates (standardized incidence ratio [SIR] 1.54; 95% CI, 1.29–1.82), but almost as large
an increase in fractures at other sites (SIR 1.35; 95% CI, 1.13–1.59) [67]. Likewise, women who were premenopausal at the time of surgery had an increased risk of distal forearm (SIR 1.4, 95% CI 1.0-2.0) and vertebral
fractures (SIR 1.9, 95% CI 1.3-2.8), but not hip fracture (SRI 1.1, 95% CI 0.6-1.9) [29].

However, oophorectomy at time of hysterectomy was not found to be associated with hip fracture in either the Nurses’ Health Study or the Women’s Health Initiative Observational Study [25,27]. (See 'Studies regarding
elective oophorectomy' above.)

CLINICAL DECISION-MAKING — The decision regarding elective oophorectomy at time of hysterectomy for benign indications relies on an understanding of genetic risk factors for cancer. The approach to decisions must
include comprehensive counseling regarding risks and benefits and shared decision-making between the clinician and patient.

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The first step is to determine whether the choice regarding oophorectomy is truly elective (see 'Indications for oophorectomy' above). All women planning hysterectomy should be assessed for risk factors for ovarian and
breast cancer. In addition, an appropriate evaluation for extrauterine pelvic pathology should be performed. Strategies for cancer risk reduction in women at high risk of ovarian cancer due to hereditary ovarian and breast
cancer syndromes are discussed separately. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal cancer", section on 'Cancer risk reduction' and "Management
of patients at high risk for breast and ovarian cancer".)

Bilateral oophorectomy is associated with a small absolute cancer risk reduction for women who are at an average risk of ovarian or breast cancer. Ovarian cancer is not a common disease and hysterectomy itself provides a
small preventive effect. Removal of the fallopian tube may provide added risk reduction. Some data suggest an association between oophorectomy and decreased risk of breast cancer in women who are younger than 45
years, but no decrease in breast cancer mortality has been found. (See 'Ovarian cancer risk reduction' above and 'Breast cancer risk reduction' above.).

There are conflicting data on long-term health effects of elective oophorectomy beyond ovarian and breast cancer risk reduction. The best available data are from observational studies, some of which conflict with each
other. Given the current evidence, elective oophorectomy may be associated with an increase in long-term risks of all-cause mortality and cardiovascular disease, particularly in women who are younger than 45 to 54 years
at the time of surgery (see 'All-cause mortality' above and 'Cardiovascular disease and stroke' above). Cognitive impairment, parkinsonism, psychiatric symptoms, sexual dysfunction, and osteoporosis are additional risks.
(See 'Cognitive function and neurologic disease' above and 'Depression and anxiety' above and 'Sexual dysfunction' above and 'Osteoporosis' above.)

In the short-term, premenopausal women who undergo bilateral oophorectomy will experience the abrupt onset of menopause and will typically have bothersome menopausal symptoms (eg, hot flashes, sleep disturbance,
and mood changes). These symptoms may be treated with postmenopausal estrogen therapy; significant risks of therapy have not been demonstrated in premenopausal women. Withholding estrogen therapy from young
women who experience premature or early menopause due to oophorectomy, however, may, on the other hand, pose significant risks, based on the evidence presented here. (See "Menopausal hormone therapy: Benefits
and risks".)

For women who have already experienced natural menopause, elective bilateral oophorectomy may be health neutral. Although, a decision analysis based upon a comprehensive review of observational data concluded that
ovarian conservation at time of benign hysterectomy until age 65 years benefits long-term survival, and that the risks and benefits of elective oophorectomy approximate each other after age 65 years [68].

The American College of Obstetrics and Gynecology (ACOG) advises strong consideration of ovarian conservation at time of hysterectomy in premenopausal women who are not at an increased genetic risk of ovarian
cancer [4]. They advise consideration of oophorectomy at time of hysterectomy in women who are postmenopausal or who have a condition that may benefit from oophorectomy (eg, endometriosis, pelvic inflammatory
disease, chronic pelvic pain).

Given these considerations and the available data, for most women who undergo hysterectomy for benign indications in the absence of ovarian pathology or a familial cancer syndrome, we suggest ovarian conservation and
discussion regarding removal of the fallopian tubes. Oophorectomy is reasonable for women who place a higher priority on ovarian cancer prevention than on other long-term health risks, particularly those who are 51 years
old or older.

The decision regarding salpingo-oophorectomy is more difficult for women who have some risk factors for ovarian cancer (table 2), but who do not have a hereditary cancer syndrome. Ovarian cancer risk assessment tools
have been proposed, but are not well validated. As an example, one case control study found a 4 percent lifetime increased risk of ovarian cancer in women with five or more of the following risk factors: Jewish ethnicity, less
than one year of oral contraceptive use, nulliparity, no breastfeeding, no tubal ligation, painful periods or endometriosis, polycystic ovarian syndrome or obesity, and talc use [69]. Counseling of such patients believed to be at
intermediate risk of ovarian cancer must be individualized, and should include a full discussion of all of the advantages and disadvantages of elective oophorectomy versus elective salpingectomy versus elective salpingo-
oophorectomy. (See 'Ovarian cancer risk reduction' above.)

ESTROGEN THERAPY AFTER OOPHORECTOMY — Women experiencing premature or early menopause due to bilateral oophorectomy at the time of hysterectomy are different from women who reach menopause at the
median age of 51 years, and data regarding the use of hormone therapy in naturally menopausal women should not be extrapolated to women who have surgical menopause at the time of hysterectomy [70,71].
Observational data consistently indicate that several of the serious long-term health consequences of bilateral oophorectomy can be ameliorated by taking estrogen therapy until at least age 50 to 51 years [28,44,53].

Women who are treated with hormone therapy after hysterectomy may take estrogen therapy alone, since a progestogen for endometrial protection is not needed. Among women under 60 years of age, risks associated with
hormone therapy in the Women's Health Initiative were greater in women taking estrogen plus progesterone as compared with the minimal to no risks associated with hormone therapy in women taking estrogen alone [72].
Following bilateral oophorectomy, some clinicians treat women with androgen therapy for sexual dysfunction; other indications for androgens in this population are not well established and concern for increased risk of breast
cancer and cardiovascular disease has been raised [73,74]. (See "Sexual dysfunction in women: Management", section on 'Androgens'.)

SUMMARY AND RECOMMENDATIONS

● Many premenopausal women undergo oophorectomy at the time of hysterectomy but rarely without an indication. It has been common practice to counsel women who were planning hysterectomy for benign indications,
particularly in their mid-40s or older, to undergo concomitant bilateral oophorectomy. This recommendation is now replaced by consideration of elective salpingectomy for women at general population risk of ovarian
cancer in the absence of other benign ovarian pathology. (See 'Introduction' above.)

● Elective oophorectomy refers to the removal of the ovaries in a woman who has no known indication for this procedure (eg, ovarian pathology, hereditary ovarian cancer syndrome). Risk-reducing salpingo-
oophorectomy refers to the removal of the tubes and ovaries in a woman at high risk of ovarian or breast cancer due to a known gene mutation. (See 'Terminology' above.)

● Oophorectomy is associated with a reduction in the risk of ovarian cancer. Some data suggest that breast cancer risk is probably reduced in women who are premenopausal at time of surgery but only if performed
before age 47.5. (See 'Ovarian cancer risk reduction' above and 'Breast cancer risk reduction' above.)

● Oophorectomy appears to increase long-term mortality and cardiovascular risk in women under the age of 45 to 50 years who do not take estrogen therapy. (See 'Long-term health risks' above.)

● Oophorectomy, particularly before menopause, has potential deleterious effects on the risk for cognitive decline, parkinsonism, depression and anxiety, glaucoma, sexual dysfunction and osteoporotic fractures. (See
'Cognitive function and neurologic disease' above and 'Depression and anxiety' above and 'Sexual dysfunction' above.)

● For most women who undergo hysterectomy for benign indications, in the absence of ovarian pathology or a familial cancer syndrome, we suggest ovarian conservation (Grade 2C). We also recommend that there be a
discussion about elective salpingectomy with ovarian preservation. Oophorectomy is reasonable, particularly for those who are 51 years of age or older, for women who place a higher priority on ovarian cancer
prevention than on the potential risks of mortality and cardiovascular disease that have been suggested by some studies. (See 'Clinical decision-making' above and "Opportunistic salpingectomy for ovarian, fallopian
tubal, and peritoneal carcinoma risk reduction".)

● Counseling of women with risk factors for ovarian cancer (table 2), but who do not have a hereditary cancer syndrome, must be individualized. (See 'Clinical decision-making' above.)

● Women who undergo oophorectomy inducing premature (before age 40 years) or early (before age 45 years) menopause are likely to benefit from estrogen therapy until they reach the average age of natural
menopause. (See 'Estrogen therapy after oophorectomy' above and "Management of spontaneous primary ovarian insufficiency (premature ovarian failure)".)

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45. Vajaranant TS, Grossardt BR, Maki PM, et al. Risk of glaucoma after early bilateral oophorectomy. Menopause 2014; 21:391.
46. Pasquale LR, Kang JH. Female reproductive factors and primary open-angle glaucoma in the Nurses' Health Study. Eye (Lond) 2011; 25:633.
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Topic 14198 Version 12.0

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GRAPHICS

Estimated cancer risks associated with BRCA1 and BRCA2 mutations

Cancer type Risk in BRCA1/2 carriers to age 70 years General population risk to age 70 years Comments

Breast 40 to 75 percent 7 percent The range of risk reported in the literature is wide. In most
studies, risk in BRCA1 carriers is higher than that observed
in BRCA2 carriers.
The incidence of breast cancer diagnosed younger than 50
years of age is higher in BRCA1 carriers compared with
BRCA2 carriers, but both groups have an increased risk of
premenopausal breast cancer, as well as increased lifetime
risks.

Contralateral (opposite) breast
BRCA1: up to 65 percent 0.5 to 1 percent per year after diagnosis Risk is affected by other factors such as tamoxifen use and
BRCA2: up to 50 percent oophorectomy (ovary removal).
For BRCA1/2 carriers who have had lumpectomy: Risk of
developing a second breast cancer in the affected breast
appears to be elevated over long follow-up periods.

Ovarian BRCA1: Approximately 40 percent
BRCA2: Approximately 15 percent
<1 percent The risk estimates provided here are representative of
findings from multiple studies.
The incidence of ovarian cancer diagnosed younger than 50
years of age is higher in BRCA1 carriers, and overall rare in
all carriers younger than 40 years old; risk of fallopian tube
cancer is also substantially elevated.

Colon Unclear 2 percent If elevated, risk is small; studies have not been consistent
about whether risk is elevated.

Prostate Elevated; absolute risk not well defined 8 percent Whites Risk appears to be higher in BRCA2 carriers and possibly in
12 percent African Americans men younger than 65 years old.

Male breast Elevated but <10 percent <1 percent Risk appears to be higher in BRCA2 carriers; rarely occurs
in men younger than age 50.

Pancreatic Elevated but <10 percent <1 percent Risk appears to be higher in BRCA2 carriers.

Other sites To be determined Varied These sites may include cancer of the stomach and skin
(melanoma).

These risks are estimates based upon review of the literature. Specific studies have reported risks that are lower or higher than the ranges or estimates quoted; however, the estimates reported here are representative of findings from
high-quality studies. Risks will also vary based on an individual's current age and other risk factors.

Graphic 68548 Version 8.0

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Lynch syndrome cancer risk

Lifetime risk for colon, endometrial, and ovarian cancer in individuals compared
with the general population.

Data from:
1. Koornstra JJ, Mourits MJ, Sijmons RH, et al. Management of extracolonic
tumours in patients with Lynch syndrome. Lancet Oncol 2009; 10:400.
2. Barrow E, Robinson L, Alduaij W, et al. Cumulative lifetime incidence of
extracolonic cancers in Lynch syndrome: a report of 121 families with proven
mutations. Clin Genet 2009; 75:141.

Graphic 57830 Version 4.0

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Risk factors for ovarian cancer

Relative risk Lifetime probability, percent [1]

General population 1.0 1.4 [1]

BRCA1 gene mutation 35 to 46 [2]

BRCA2 gene mutation 13 to 23 [2]

Lynch syndrome (hereditary nonpolyposis colon cancer) 3 to 14 [3,4]

Family history of ovarian cancer (with negative testing for a familial ovarian cancer syndrome) Uncertain [5,6]

Infertility 2.67 [7]

Polycystic ovarian syndrome 2.52 [8]

Endometriosis (increase in risk of clear cell, endometrioid, or low grade serous carcinomas) 2.04 to 3.05 [9]

Cigarette smoking (increase in risk of mucinous carcinoma) 2.1 [10]

Intrauterine device 1.76 [11]

Past use of oral contraceptives 0.73 [12]

Past breast feeding (for >12 months) 0.72 [13]

Tubal ligation 0.69 [14]

Previous pregnancy 0.6

References:
1. http://seer.cancer.gov/statfacts/html/ovary.html.
2. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25:1329.
3. Koornstra JJ, Mourits MJ, Sijmons RH, et al. Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol 2009; 10:400.
4. Barrow E, Robinson L, Alduaij W, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: A report of 121 families with proven mutations. Clin Genet 2009; 75:141.
5. Kauff ND, Mitra N, Robson ME, et al. Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families. J Natl Cancer Inst 2005; 97:1382.
6. Lee JS, John EM, McGuire V, et al. Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations. Cancer Epidemiol Biomarkers Prev 2006; 15:359.
7. Ness RB, Cramer DW, Goodman MT, et al. Infertility, fertility drugs, and ovarian cancer: A pooled analysis of case-control studies. Am J Epidemiol 2002; 155:217.
8. Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S. Polycystic ovary syndrome and the risk of gynaecological cancer: A systematic review. Reprod Biomed Online 2009; 19:398.
9. Pearce CL, Templeman C, Rossing MA, et al. Association between endometriosis and risk of histological subtypes of ovarian cancer: A pooled analysis of case-control studies. Lancet Oncol 2012; 13:385.
10. Jordan SJ, Whiteman DC, Purdie DM, et al. Does smoking increase risk of ovarian cancer? A systematic review. Gynecol Oncol 2006; 103:1122.
11. Tworoger SS, Fairfield KM, Colditz GA, et al. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 2007; 166:894.
12. Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, et al. Ovarian cancer and oral contraceptives: Collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and
87,303 controls. Lancet 2008; 371:303.
13. Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality's evidence report on breastfeeding in developed countries. Breastfeed Med 2009; 4 Suppl 1:S17.
14. Cibula D, Widschwendter M, Májek O, Dusek L. Tubal ligation and the risk of ovarian cancer: Review and meta-analysis. Hum Reprod Update 2011; 17:55.

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Risk assessment criteria for inherited breast-ovarian cancer syndome, combining several guidelines

Non-Jewish families
Any of the following:

One case of breast cancer ≤40 years old in a first- or second-degree relative

One first- or second-degree relative with breast and ovarian cancer, at any age

Two or more cases of breast cancer in first- or second-degree relatives if one is diagnosed at ≤50 years old, or is bilateral cancer

One first- or second-degree relative with breast cancer at ≤50 years old, or bilateral breast cancer, and one first- or second-degree relative with ovarian cancer

Three cases of breast and ovarian cancer (at least one case of ovarian cancer) in first- or second-degree relatives

Two cases of ovarian cancer in first- or second-degree relatives

One case of male breast cancer in a first- or second-degree relative if another first- or second-degree relative has (male or female) breast or ovarian cancer

Jewish families
Any of the following:

One or more cases of breast cancer ≤50 years old in a first- or second-degree relative

One or more cases of ovarian cancer at any age in a first- or second-degree relative

One or more first- or second-degree relatives with breast cancer at any age, if another first- or second-degree relative has breast and/or ovarian cancer at any age

One or more cases of male breast cancer in a first- or second-degree relative

Adapted from: Hampel H, et al. J Med Genet 2004; 41:81.

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Amsterdam II criteria for Lynch syndrome

There should be at least three relatives with any Lynch syndrome-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis)

One should be a first-degree relative of the other two

At least two successive generations should be affected

At least one should be diagnosed before age 50

Familial adenomatous polyposis should be excluded in the colorectal cancer case(s), if any

Tumors should be verified by pathological examination

Adapted from Vasen HF, Watson P, Mecklin JP, et al. Gastroenterology 1999; 116:1453.

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Contributor Disclosures
Susan D Reed, MD, MPH Grant/Research/Clinical Trial Support: Bayer Pharmaceuticals [Uterine fibroids, endometriosis, uterine perforation (Levonorgestrel IUS)]. Barbara Goff, MD Employment (Spouse): Lilly [General
oncology (Gemcitabine, pemetrexed)] - No relevant conflict on topics. Howard T Sharp, MD Nothing to disclose Sandy J Falk, MD, FACOG Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to
support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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