INTRODUCTION — Hysterectomy can be performed with or without the removal of the ovaries and/or fallopian tubes. Historically, it had been common practice to counsel patients in their mid-40s or older who were planning hysterectomy for benign indications to undergo concomitant bilateral salpingo-oophorectomy (BSO). The rationale for oophorectomy in these patients was to reduce the risks of ovarian cancer and reoperation for ovarian pathology, and the short interval to spontaneous menopause. This approach also assumed nearly universal treatment with postmenopausal hormone therapy.
However, with a growing understanding of the potential long-term health consequences of elective oophorectomy, and the potential advantages of elective salpingectomy alone (without oophorectomy), the pendulum has swung toward ovarian conservation, particularly in premenopausal patients . Randomized trials comparing elective oophorectomy and ovarian conservation are lacking, therefore clinicians rely on data from cohort studies for patient counseling.
The management of the ovaries at the time of hysterectomy for benign disease will be reviewed here. Opportunistic salpingectomy, techniques for salpingectomy and oophorectomy, management of patients with gynecologic malignancy or those with a hereditary ovarian cancer syndrome, and general principles of menopause are discussed separately.
●Elective oophorectomy – Removal of the ovaries in a patient who has no known medical indication for this procedure (eg, ovarian pathology, hereditary ovarian cancer syndrome). Elective salpingo-oophorectomy (removal of the ovaries and fallopian tubes) may also be performed in such patients.
While the term "elective" is widely used in the literature, other terms, such as "opportunistic," "concurrent," or "incidental" may also be used. In this topic, we retain the term "elective" in most instances to emphasize shared decision-making and patient choice.
●Opportunistic salpingectomy – Removal of the fallopian tubes in a patient with a general population risk of ovarian cancer syndrome. Risk reduction occurs because many malignancies currently categorized as ovarian cancers may arise in the tubal epithelium. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction".)
●Risk-reducing salpingo-oophorectomy – Removal of the ovaries and fallopian tubes in a patient with a hereditary ovarian cancer syndrome. (See "Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer".)
Risk-reducing salpingectomy with delayed oophorectomy has also been described in selected patients. (See "Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer", section on 'BSO versus salpingectomy alone'.)
The term prophylactic salpingo-oophorectomy has been used inconsistently in the literature and will not be used in this topic, 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 patients at an average risk or those with a hereditary ovarian cancer syndrome [2,3].
HOW TO CHOOSE — The approach to oophorectomy at time of hysterectomy for benign indications must be individualized and includes comprehensive counseling regarding risks and benefits and shared decision-making between the clinician and patient.
Pelvic pathology — Patients undergoing hysterectomy for benign indications should be evaluated for extrauterine pelvic pathology (eg, with physical examination and/or pelvic imaging). Indications for concurrent oophorectomy may include:
●Benign ovarian neoplasms – Benign ovarian neoplasms (eg, mature cystic teratoma, serous cystadenoma, mucinous cystadenoma) and management with oophorectomy versus ovarian cystectomy are reviewed separately. (See "Adnexal mass: Differential diagnosis", section on 'Benign neoplasms' and "Oophorectomy and ovarian cystectomy", section on 'Oophorectomy versus cystectomy'.)
●Endometriosis – The risk of reoperation for endometriosis-related concerns appears to be lower if the ovaries are removed at the time of hysterectomy [4,5]. (See "Endometriosis: Treatment of pelvic pain", section on 'Surgical treatment options'.)
In a retrospective study of nearly 4500 patients undergoing hysterectomy for endometriosis, patients with ovarian conservation compared with oophorectomy were more likely to undergo at least one reoperation (13 versus 5.3 percent) during the 10-year (median) follow-up period . Oophorectomy and adhesiolysis were the most common reoperation procedures.
●Tubo-ovarian abscess – In patients requiring surgical management of tubo-ovarian abscess, the risk of reoperation is higher if one or both ovaries are conserved . (See "Management and complications of tubo-ovarian abscess", section on 'Drainage and surgery'.)
●Pelvic adhesions/pelvic pain – Preoperative pelvic adhesions and/or pelvic pain are risk factors for residual ovary syndrome (ROS), which is characterized by pelvic pain in a patient in whom an ovary was intentionally left in place during hysterectomy. In one study, the incidence of ROS was reported to be between 0.9 to 3.4 percent . However, the majority of such patients underwent open abdominal hysterectomy, and these data may not be transferable to patients today, who are more likely to undergo a laparoscopic procedure.
While hysterectomy with bilateral salpingo-oophorectomy (BSO) is a common approach for such patients, patients should be counseled that if hysterectomy is performed alone, subsequent oophorectomy can frequently be accomplished with a laparoscopic approach .
ROS differs from ovarian remnant syndrome (ORS) which is defined as the presence of ovarian tissue in a patient who has had previous oophorectomy. (See "Ovarian remnant syndrome".)
Oophorectomy in these contexts is not elective. However, even in these circumstances, patients should be counseled preoperatively about the risk-to-benefit balance of bilateral oophorectomy versus ovarian conservation.
Menopausal status — The choice of oophorectomy or ovarian conservation at the time of hysterectomy also depends on the patient's age and menopausal status.
●For most premenopausal patients who undergo hysterectomy for benign indications, we suggest ovarian conservation. While bilateral oophorectomy provides a small absolute cancer risk reduction for patients at an average risk of ovarian or breast cancer, it is associated with long-term health consequences. (See 'Benefits of elective oophorectomy' below and 'Long-term health risks' below.)
However, elective oophorectomy may be reasonable for patients who place a higher priority on ovarian cancer prevention than on other long-term health risks, particularly those who are age 51 years old or older [9,10].
●For menopausal patients, elective bilateral oophorectomy may be health neutral. In a decision analysis based on a comprehensive review of observational data, the risks and benefits of elective oophorectomy compared with ovarian conservation at time of hysterectomy approximated each other after age 65 years . Ovarian conservation until age 65 years benefited long-term survival. However, in a revised analysis of these data, those who had hysterectomy with or without oophorectomy at ≥50 years had similar survival to age 80 years . The results of these models may not be applicable to all patients as the study cohorts included mostly White patients and salpingectomy status was unknown. (See 'All-cause mortality' below.)
Ovarian cancer risk factors — All patients should be assessed for risk factors for ovarian and breast cancer. This is especially important when pelvic surgery is planned (table 1 and table 2). (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors".)
Patients for whom a familial cancer syndrome is suspected should be offered genetic counseling and testing (table 2 and table 3). (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes".)
For patients with some risk factors, but who do not have, or have not been tested for, a hereditary cancer syndrome, the decision regarding oophorectomy is more nuanced. Counseling must be individualized and include a detailed discussion of the advantages and disadvantages of elective oophorectomy, opportunistic salpingectomy, and elective salpingo-oophorectomy.
BENEFITS OF ELECTIVE OOPHORECTOMY
Ovarian cancer risk reduction — Bilateral oophorectomy reduces, but does not eliminate, the risk of developing ovarian cancer. Removal of the fallopian tubes provides additional risk reduction and there is an abundance of data demonstrating that the fallopian tubes, rather than the ovaries, are the primary site of most epithelial, fallopian tube, and peritoneal carcinomas (EOC). EOC discovered incidentally at the time of bilateral salpingo-oophorectomy (BSO) has also been described. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Incidental finding'.)
The degree of ovarian cancer risk reduction from BSO at the time of hysterectomy in the general population has been illustrated in the following studies:
●The Nurses' Health study (NHS) was a prospective cohort study including approximately 30,000 participants who had a hysterectomy for benign disease with or without ovarian conservation [12,13]. The average age at time of surgery was 43 to 47 years and the average age at enrollment was 51 years; the majority (94 percent) of subjects were White. Subjects were followed for up to 28 years, allowing adequate time to assess outcomes that are more common for patients over age 60 years, including cardiovascular disease (CVD) and stroke, chronic kidney disease, dementia, osteoporosis, breast cancer, ovarian cancer, and all-cause mortality (see 'Long-term health risks' below). Given the small gap between surgery and enrollment, and the long follow-up duration, we regard the NHS as having some of the best available data on this subject.
During the 28 years of follow-up, patients who underwent hysterectomy with bilateral oophorectomy compared with hysterectomy alone had fewer ovarian cancer-related deaths (4 versus 44 patients; hazard ratio [HR] 0.06, 95% CI 0.02-0.17) . The analyses were adjusted for family history of ovarian cancer and duration of oral contraceptive use.
●The Women's Health Initiative (WHI) Observational Study was a prospective study that included 25,448 females who had a hysterectomy for benign disease; 56 percent of study participants had concomitant BSO . Individuals in this study were initially invited to participate in the WHI randomized trial that evaluated postmenopausal hormone therapy but were either found ineligible or declined to participate in the trial. The average age at time of hysterectomy was 49 years or younger, and the average age at enrollment was 63 years; 82 percent of the subjects were White. Subjects were followed for only eight years.
During the 7.6 years (average) of follow-up, patients in the BSO group compared with the ovarian conservation group had fewer cases of incident ovarian cancer (2 versus 33 per 10,000 females) .
Limitations of the WHI Observational Study include:
•Short duration of follow-up (8 years compared with 28 years in the NHS).
•A long gap between surgery and enrollment (average 14 years).
•Potential for recall bias, which likely affects risk estimates.
•Patients who had outcomes of interest (CVD 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.
•The study also reported that BSO did not have significant adverse effects on all-cause mortality, coronary heart disease, hip fracture, or cancer, but the study had insufficient statistical power to detect such differences.
●In a subsequent cohort study including over 195,000 patients undergoing hysterectomy between 1996 and 2010 in Canada, 24 percent of patients underwent concomitant BSO . The cumulative 20-year incidence rate of ovarian cancer was lower among patients in the BSO group compared with the ovarian (and tubal) conservation group (0.08 versus 0.46 percent; absolute risk difference [ARD] 0.38 percent, 95% CI 0.32-0.45). In a subgroup analysis including patients ≥50 years, the ARD was slightly higher (0.62 percent, 95% CI 0.47-0.77). This study did not include patients who underwent bilateral salpingectomy with ovarian preservation at the time of hysterectomy in the analysis.
By contrast, unilateral oophorectomy has not been proven to reduce the risk of ovarian cancer. In a multicenter case-control study between 1992 and 1999 and including 1031 patients with ovarian cancer, rates of prior unilateral oophorectomy or unilateral oophorectomy plus hysterectomy were similar between groups . However, in another case-control study including 129 patients with ovarian cancer, patients with a history of unilateral oophorectomy compared with controls had a decreased rate of ovarian cancer (2.9 versus 13.6 percent, odds ratio [OR] 0.2; 95% CI 0.04-0.7) over the 16-year study period . Further study of this issue is needed.
Breast cancer risk reduction — Bilateral oophorectomy reduces the risk of breast cancer, although the age at which this benefit occurs is uncertain [18,19]. The reduced risk of breast cancer is likely due to reduced exposure to reproductive hormones (ie, estrogen and progesterone) from the premenopausal ovaries; taking hormone therapy following bilateral oophorectomy does not affect the risk reduction associated with oophorectomy . This effect is also seen in patients at high risk of breast cancer. (See "Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer", section on 'Candidates'.)
●In the NHS, oophorectomy was associated with a reduction in breast cancer incidence only in patients who underwent the procedure at age 47.5 years or younger .
●By contrast, in the WHI Observational Study, a reduction in breast cancer risk only occurred in patients who underwent oophorectomy at age <40 years and did not take estrogen therapy .
●In a retrospective study including over 49,000 patients at average risk for breast cancer who underwent hysterectomy for benign disease and were followed for a median of 4.5 years, those who had concomitant BSO compared with those who underwent hysterectomy alone had a lower risk of developing breast cancer (HR 0.86, 95% CI 0.75-0.98) after controlling for age, race, income, and comorbidities . Rates of incident breast cancer were lower for patients with BSO in every age group except those ≥60 years.
The effect of menopausal hormone therapy (MHT) on breast cancer risk is discussed separately. (See "Menopausal hormone therapy: Benefits and risks", section on 'Breast cancer'.)
Effects on other cancers — The effect of oophorectomy on the development of other cancers is less clear.
In the WHI Observational Study, patients undergoing oophorectomy compared with ovarian conservation had similar rates of lung and colorectal cancers . By contrast, in the NHS study, patients undergoing oophorectomy had higher rates of lung cancer (HR 1.26, 95% CI 1.02-1.56) but similar rates of colorectal cancers . In a subsequent cohort study evaluating the risk of cancer and premenopausal oophorectomy, those undergoing oophorectomy (1562 patients) compared with age-matched referent controls had a similar risk of lung and colorectal cancers during the 18-year (median) follow-up period .
Avoiding the need for subsequent oophorectomy — Reoperation for ovarian pathology occurs in 3 to 9 percent of patients who retain one or both ovaries after hysterectomy [7,22,23]. However, for most patients undergoing hysterectomy, the possible need for subsequent surgery does not appear to justify the deleterious long-term consequences of oophorectomy. (See 'Consequences of elective oophorectomy' below.)
The Mayo Clinic Cohort Study of Oophorectomy and Aging (MOA) is the largest study to report the risk of subsequent oophorectomy following hysterectomy . In this retrospective study of approximately 10,000 subjects, patients with versus without a history of hysterectomy had a higher rate of oophorectomy at 30 years of follow-up (9.2 versus 7.3 percent, HR 1.2, 95% CI 1-1.4). The cumulative incidence of subsequent oophorectomy at 30 years for patients with one preserved ovary or with both ovaries intact was 4 and 10.6 percent, respectively. Other studies that reported lower risk of reoperation had short follow-up, were not population based, and lacked a control group [7,22].
Some data suggest that the reoperation rate is higher in patients who undergo abdominal or laparoscopic hysterectomy compared with vaginal hysterectomy . The reason for such a difference is uncertain, but it may be that vaginal hysterectomy is typically not performed when ovarian pathology is suspected.
For patients in whom subsequent oophorectomy is required, a laparoscopic rather than an open abdominal technique can often be performed. In one study including 35 patients with pelvic pain after hysterectomy with ovarian conservation, almost all patients (91 percent) were able to have a successful laparoscopic oophorectomy . However, surgical adhesions from prior hysterectomy may make a laparoscopic approach difficult. In a retrospective study including 744 patients undergoing laparoscopic adnexal surgery at an academic tertiary care center, those with prior hysterectomy compared with no hysterectomy had higher rates of intraoperative (3.2 versus 0.8 percent; risk ratio [RR] 4, 95% CI 1.1–14.7) and postoperative complications (15.3 versus 9.4 percent; RR 1.6, 95% CI 1–2.6) . Patients with prior hysterectomy also had a fivefold increase in rates of conversion to laparotomy.
CONSEQUENCES OF ELECTIVE OOPHORECTOMY
Surgical menopause — Surgical menopause (caused by bilateral oophorectomy, or the removal of the remaining ovary in a patient who has previously undergone unilateral oophorectomy) results in an abrupt drop in circulating estrogen levels, abrupt rise in follicle-stimulating hormone (FSH) levels, and complete cessation of ovarian estrogen, androgen, and progesterone production [26-28]. Patients typically experience bothersome menopausal symptoms (eg, hot flashes, sleep disturbance, mood changes). When not contraindicated, these symptoms may be treated with menopausal hormone therapy; significant risks of such therapy have not been demonstrated in patients who were premenopausal at the time of oophorectomy, and withholding estrogen therapy from such patients may pose significant risks. (See 'Role of estrogen therapy after hysterectomy with oophorectomy' below and 'Long-term health risks' below and "Menopausal hormone therapy: Benefits and risks".)
This contrasts with natural menopause, which is typically characterized by a gradual waxing and waning of estradiol and FSH production, in association with unpredictable ovulatory and anovulatory cycles, that occurs over an interval of up to 10 years (though the variability in hormone levels is most dramatic over a period of four years) [29,30]. Intact postmenopausal ovaries continue to produce androgens including testosterone, androstenedione, and dehydroepiandrosterone (DHEA), and very small amounts of estradiol and estrone for many years . Although estrogen secretion by the postmenopausal ovary eventually ceases, ovarian secretion of small amounts of testosterone and DHEA may continue into the eighth decade of life [27,31].
Nonovarian sources of sex steroids include the adrenal glands and widespread target tissues, including fat, where aromatization of androgens into estrogen occurs. The extent to which nonovarian sex steroid hormone synthesis differs between patients who have experienced surgical compared with natural menopause has been debated [27,28], but it appears that total androgen levels remain lower after surgical than natural menopause .
Surgical morbidity — Operative complications are uncommon in patients undergoing elective oophorectomy at the time of hysterectomy. However, the risk of such complications is increased if adhesions or other intraabdominal pathology are present.
Risk of complications may also depend on surgical route; however, data are conflicting. For hysterectomies performed via laparotomy or laparoscopy, concomitant oophorectomy does not appreciably increase the complexity of the procedure. By contrast, when oophorectomy is combined with vaginal hysterectomy, the procedure is potentially more difficult. The degree of difficulty depends on adnexal anatomy (ie, high versus low in the pelvis), mobility, and the experience of the surgeon. Representative studies include:
●In a retrospective study of over two million patients in the United States who underwent hysterectomy for benign indications from 1998 to 2006 and identified via the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, those undergoing vaginal hysterectomy (15 percent of patients) with versus without bilateral salpingo-oophorectomy (BSO) experienced an increase in complications (odds ratio [OR] 1.12, 95% CI 1.08-1.17) . By contrast, patients undergoing abdominal (72 percent) and laparoscopic (13 percent) hysterectomy with versus without BSO had decreased rates of complications (OR 0.91, 95% CI 0.89-0.94 and OR 0.89, 95% CI 0.83-0.94, respectively).
●In a retrospective study of over nine million patients who underwent hysterectomy between 1979 and 2004 and identified via the United States National Hospital Discharge Survey database, those undergoing hysterectomy with versus without BSO had higher rates of complications (organ injury: adjusted OR 1.4, 95% CI 1-1.8; gastrointestinal complication: adjusted OR 1.8, 95% CI 1.3-2.4) . The majority (84 percent) of the procedures were open abdominal hysterectomies, which no longer reflects current practice patterns. Furthermore, the authors pooled complications from laparoscopic and vaginal procedures for the remaining 16 percent of patients.
Because available data do not consider the indication for oophorectomy (eg, pelvic adhesions, large pelvic mass), the potential effect of adnexal pathology on surgical morbidity is unknown. Therefore, further study regarding the impact of oophorectomy on surgical morbidity at the time of benign hysterectomy is needed.
Surgical risk of opportunistic salpingectomy, as well as the procedures for adnexal removal or conservation, are discussed in detail separately. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction", section on 'Perioperative outcomes' and "Hysterectomy: Abdominal (open) route", section on 'Adnexal conservation or removal' and "Hysterectomy: Laparoscopic", section on 'Adnexa' and "Hysterectomy: Vaginal", section on 'Adnexal evaluation and surgery'.)
Long-term health risks — Accumulating evidence indicates that surgical removal of the ovaries may be associated with serious long-term health consequences [12-14,34-42]. Such risks may also be greater for patients who are younger at the time of oophorectomy and those not taking estrogen therapy [35-38,41,42].
The highest quality data regarding long-term health outcomes of elective oophorectomy compared with ovarian conservation at time of hysterectomy are from prospective and retrospective studies. No randomized trials have investigated this issue . Potential long-term health effects are discussed in the following sections.
All-cause mortality — Bilateral oophorectomy at younger age appears to be associated with increased all-cause mortality [13,19,20,34,35,44-46], especially among patients who do not take estrogen therapy. While the mechanism of this effect is unknown, evidence is suggestive that hypoestrogenism may be an important factor leading to endothelial dysfunction.
The association of BSO at the time of hysterectomy with an increase in all-cause mortality has been illustrated in the following studies:
●In the Nurses' Health Study (NHS), patients who underwent bilateral oophorectomy compared with ovarian conservation had higher all-cause mortality (16.8 versus 13.3 percent, hazard ratio [HR] 1.13, 95% CI 1.06-1.21) over 28 years of follow-up . Among patients <50 years, the increased mortality risk associated with oophorectomy was seen primarily in patients who never used estrogen therapy, whereas there was little to no impact on mortality in patients who had ever used, or were currently using, estrogen therapy.
●In the United Kingdom study, a retrospective study of a United Kingdom national database including 113,679 patients ages 35 to 45 years old who underwent hysterectomy for benign conditions from 2004 to 2014, conservation of at least one ovary was associated with a lower all-cause mortality (0.6 versus 1 percent; HR 0.64, 95% CI 0.55-0.73) . While the finding was statistically significant, the absolute difference was quite small (0.4 percent).
●In the Australian Longitudinal Study on Women's Health including over 3300 females with a history of hysterectomy prior to age 50 years, the mortality rate was higher for those who underwent concomitant oophorectomy compared with hysterectomy alone (40 versus 32 deaths per 10,000 person-years) . The between-group difference in mortality was highest among patients not receiving hormone therapy (74 versus 30 deaths per 10,000 person-years), whereas there was no between-group difference among patients taking hormone therapy (35 deaths per 10,000 in each group).
●The Mayo Clinic Cohort Study of Oophorectomy and Aging (MOA) was a retrospective population-based cohort study of 2365 patients in Olmstead County, Minnesota who underwent unilateral or bilateral oophorectomy for benign disease; almost all the patients were White [35,45]. For some analyses, patients from the cohort were compared with controls who had not had an oophorectomy and were identified via random digit telephone dialing . The median age at time of surgery was 44 years among premenopausal patients who had a bilateral oophorectomy and 62 years among postmenopausal patients. Patients 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 surgical, pharmacy, and outcome data for all participants. Thus, recall bias was limited and there was access to long-term follow-up data. This was also the only study to analyze elective and indicated oophorectomies separately.
In this study, an increase in all-cause mortality compared with referent patients without oophorectomy was found only in those patients in whom the oophorectomy was indicated due to a benign tumor or inflammation; the causes of death were not reported [35,45]. Among patients <45 years, mortality during the 25 years of follow-up was higher for patients who underwent prophylactic oophorectomy compared with those who did not have an oophorectomy (27 versus 16 percent; HR 1.67, 95% CI 1.16-2.4). The increased mortality risk associated with oophorectomy was seen primarily in patients who did not receive estrogen therapy. The study lacked sufficient statistical power to detect a difference in outcome in other patients who underwent prophylactic oophorectomy. Further study of the distinction between indicated and elective oophorectomies is needed. (See 'Pelvic pathology' above.)
●In a retrospective study including over 49,000 patients at average risk for breast cancer who underwent hysterectomy for benign disease and were followed for a median of 4.5 years, all-cause mortality was higher for patients who underwent BSO compared with hysterectomy alone (3.1 versus 1.2 percent); this association persisted across all age groups .
By contrast, in the Women's Health Initiative (WHI) Observational Study, patients who underwent hysterectomy with bilateral oophorectomy compared with ovarian conservation had no increase in mortality for any age group subset . A discussion of this study’s limitations can be found above. (See 'Ovarian cancer risk reduction' above.)
Cardiovascular disease — Bilateral oophorectomy at a younger age and early (40 to 45 years) or premature (<40 years) menopause appear to be associated with an increased risk of cardiovascular disease (CVD), including coronary heart disease and stroke [13,19,34,41,47-52]. Estrogen therapy, however, may mitigate these adverse effects in such patients [12,38,48,50]. This is discussed in detail separately. (See "Menopausal hormone therapy and cardiovascular risk".)
●Early/premature menopause – The associations between CVD, oophorectomy, and early/premature menopause were illustrated in the following studies:
•In a pooled analysis of 10 observational studies including over 203,7000 postmenopausal patients, surgical compared with natural menopause was associated with higher risk of CVD (2.7 versus 1.8 CVD events per 1000 person-years; HR 1.22, 95% CI 1.16–1.28) . However, the association diminished after adjusting for age at menopause (adjusted HR [aHR] 1.05, 95% CI 1.03-1.06). Lower age at menopause was associated with an increased incident of CVD in both groups, but use of hormone therapy mitigated this risk. (See 'Role of estrogen therapy after hysterectomy with oophorectomy' below.)
Similarly, surgical menopause at age <35 years compared with natural menopause occurring at age 50 to 54 years was associated with increased risk of stroke (2 versus 0.6 events per 1000 person-years; aHR 2.6, 95% CI 2-3.3); the risk was somewhat less with surgical menopause occurring at ages 35 to 39 years (1.3 versus 0.6 events per 1000 person-years; aHR 1.9, 95% CI 1.6-2.3), and 40 to 44 years (1 versus 0.6 events per 1000 person-years; aHR 1.5, 95% CI 1.3-1.8) . While other studies have not reported this association [52,54], they were limited by the inability to ascertain use of hormone therapy or small numbers of subjects.
•Earlier studies reported that CVD risk with earlier menopause was limited to current smokers , while a 2005 study reported the effect in patients who never smoked . (See "Overview of atherosclerotic cardiovascular risk factors in females", section on 'Early menopause'.)
By contrast, in the WHI Observational Study, patients with hysterectomy plus BSO compared with ovarian conservation, at any age, had similar rates of CVD . However, the lack of increased risk for CVD with BSO could be explained by the following: Nearly 80 percent of patients were >40 years at the time of BSO, 66 percent were current users of estrogen therapy, and over 60 percent had used estrogen therapy for >5 years. Other limitations of this study are detailed above. (See 'Ovarian cancer risk reduction' above.)
●Menopausal transition – There may not be an increased risk for CVD among patients who undergo BSO in the menopause transition.
In the Study of Women's Health Across the Nation, a prospective cohort study including over 3000 premenopausal patients (ages 42 to 52 years) not using hormone therapy and followed annually for up to 11 years, those undergoing hysterectomy with (5.4 percent) versus without (3.9 percent) BSO had similar changes in CVD risks factors including lipids, insulin resistance, blood pressure, hemostatic, and inflammatory factors . Similarly, in the United Kingdom cohort study discussed above, patients with oophorectomy in the menopause transition compared with those who experienced natural menopause had similar CVD outcomes .
Chronic kidney disease — Oophorectomy prior to age 50 appears to be associated with an increased risk of chronic kidney disease (CKD), and the relationship between early menopause and CKD appears to be bidirectional. The mechanism that confers this relationship, however, is unclear. It is hypothesized that the potential increased risk for CKD associated with young age at bilateral oophorectomy is due to endothelial dysfunction, glomerulosclerosis, and increased glomerular permeability.
In the Mayo Clinic Cohort Study of Oophorectomy and Aging (MOA-2), patients who underwent oophorectomy prior to age 50 years compared with those who did not had a higher risk of CKD (aHR 1.42, 95% CI 1.14-1.77); the risk was highest in patients ≤45 years (aHR 1.59, 95% CI 1.15-2.19) . Hormone replacement therapy seemed to mitigate some of this risk; in patients ≤45 years, the aHR was lower in those who took hormone replacement therapy (HR 1.52) compared with those who did not (HR 2.07).
Similarly, in a subsequent report from the database of the National Health and Nutrition Examination Survey, patients experiencing surgical menopause at age <45 compared with ≥45 years were more likely to have CKD (OR 1.38, 95%CI 1.1-1.8) .
Cognitive function and neurologic disease — Oophorectomy prior to menopause is associated with an increased risk of cognitive impairment or dementia, as well as parkinsonism [36,42,60-65]. Estrogen therapy may be neuroprotective in these patients. (See "Estrogen and cognitive function", section on 'Timing of exposure' and "Menopausal hormone therapy: Benefits and risks", section on 'Cognitive function and dementia'.)
●Cognitive impairment or dementia – In the Mayo Clinic Cohort Study discussed above (see 'All-cause mortality' above), among patients who underwent bilateral oophorectomy before menopause compared with those who did not undergo oophorectomy, an increased risk of cognitive impairment or dementia was restricted to those who were <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) [42,60,61]. Patients <46 years with bilateral oophorectomy compared with no oophorectomy also had increased odds of mild cognitive impairment (adjusted odds ratio [aOR] 2.2, 95% CI 1.4-3.5) and poorer performance on cognitive tests approximately 30 years later . Increased rates of dementia were also found in patients with prior oophorectomy in a large Danish cohort study , but this did not reach statistical significance.
Small observational studies have shown a decrease in specific cognitive functions after bilateral oophorectomy, including verbal fluency, verbal memory, procedural learning, and some other executive functions [36,62]. 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 .
●Parkinsonism and Parkinson disease – In the Mayo Clinic Cohort Study, patients 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 [61,63]. An increase in the risk of Parkinson disease was also found, but this did not reach statistical significance.
In a subsequent cohort study including almost 5500 patients (median age 45 years), patients with versus without a history of oophorectomy also had higher rates of examination or medical record-confirmed parkinsonism (HR 1.59; 95% CI 1.02-2.46) . While rates of Parkinson disease were similar between groups overall, rates were higher in those with oophorectomy prior to age 43 years (HR 5, 95% CI 1.1-22.7).
A case-control study including 385 females also reported an association with bilateral oophorectomy and Parkinson disease .
Depression and anxiety — Some data suggest that bilateral oophorectomy at the time of hysterectomy is associated with a long-term increased risk of developing depression or anxiety [36,42,69] but data are conflicting .
In the Mayo Clinic Cohort Study discussed above, patients who had bilateral oophorectomy compared with those who did not had an increase in onset of symptoms of depression (as diagnosed by a physician, 11 versus 7 percent) or anxiety (7 versus 3 percent) . Median time from oophorectomy to the onset of symptoms of depression or anxiety was approximately 14 years, but differences in rates of occurrence of anxiety and depression were observed within three years following hysterectomy and persisted throughout more than 30 years of follow-up.
However, data are conflicting. In a subsequent retrospective study including data from 1970 patients in the Study of Women's Health Across the Nation, patients undergoing hysterectomy with (5.2 percent) and without (3.9 percent) oophorectomy experienced a decrease in depressive and anxiety symptoms after surgery; the trajectory was similar among groups . Data from shorter-term studies have also been inconsistent regarding the effect of bilateral oophorectomy on psychological well-being [71,72].
Glaucoma — Estrogen appears to have neuroprotective effects on the optic nerve and decrease the risk of glaucoma, the second leading cause of blindness world-wide [39,40]. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
In the Mayo Clinic Cohort Study discussed above, patients with bilateral oophorectomy <43 years compared with referent controls had an increased risk of open-angle-glaucoma (as identified by diagnostic codes and confirmed in a subset chart validation study; aHR 1.6, 95% CI 1.2-2.2) . While this risk was not ameliorated in patients who took estrogen in this study, the numbers were small.
Osteoporosis — Menopause is a known risk factor for osteoporosis.
In the Mayo Clinic Cohort Study, compared with expected rates, patients who were postmenopausal at the time of oophorectomy had an increase in the risk of any osteoporotic fracture (moderate trauma fractures of the hip, spine, or distal forearm; standardized incidence ratio [SIR] 1.54, 95% CI 1.29-1.82) and fractures at other sites (SIR 1.35, 95% CI 1.13-1.59) . Similarly, patients who were premenopausal at the time of surgery had an increased risk of distal forearm (SIR 1.4, 95% CI 1-2) and vertebral fractures (SIR 1.9, 95% CI 1.3-2.8), but not hip fracture .
By contrast, oophorectomy at the time of hysterectomy was not found to be associated with hip fracture in either the NHS or the WHI Observational Study [12,14]. It is important to note the age of participants in these studies was overall lower than the peak age at which most osteoporotic fractures occur. (See 'Ovarian cancer risk reduction' above.)
Sexual dysfunction — Bilateral oophorectomy may result in sexual dysfunction, including changes in libido, arousal, orgasm, satisfaction with sex, and overall sexual outcome, particularly in patients <50 years of age or those experiencing surgical rather than natural menopause [69,75-78].
The association of bilateral oophorectomy with sexual dysfunction has been illustrated in the following studies:
●In a prospective study evaluating sexual health after treatment for heavy menstrual bleeding and including 5702 patients (mean age 39 to 45 years) undergoing hysterectomy, patients with versus without BSO experienced more loss of libido (severe: OR 1.7 versus 1.3; extreme: OR 1.8 versus 1.4) and difficult sexual arousal (severe: OR 1.8 versus 1.3; extreme: OR 1.8 versus 1.4) during the five-year study period . Patients treated with endometrial ablation served as the control group.
●In another prospective study evaluating sexual health in 1101 patients undergoing hysterectomy (the majority of whom were <50 years of age), patients undergoing BSO compared with ovarian conservation reported a 2.7-fold higher rate of not experiencing orgasm during the two-year follow-up period . Rates of vaginal dryness were similar between groups; however, the majority (88 percent) of patients undergoing concomitant oophorectomy were taking hormone therapy.
●In a cross-sectional survey including approximately 2400 females in Europe with no known increased risk of cancer, those who underwent bilateral oophorectomy compared with patients who were premenopausal or had gone through natural menopause were twice as likely to have hypoactive sexual desire symptoms (OR 2, 95% CI 1.4-3.4) .
●In a cross-sectional study including over 30,000 females in the United States, surgical, but not natural, menopause was associated with orgasm difficulties, and more patients with surgical compared with natural menopause experienced decreased in arousal . (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Age and menopause'.)
However, data are conflicting; 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 [78,81-84]. However, the majority of patients in these studies were in the menopause transition or were postmenopausal, and many were using hormone therapy.
TRENDS IN ELECTIVE OOPHORECTOMY — Given the association of elective oophorectomy with long-term adverse health consequences (see 'Long-term health risks' above), utilization of elective oophorectomy at time of hysterectomy is decreasing [1,85,86]. By contrast, opportunistic salpingectomy is not associated with such risks, and rates of salpingectomy are increasing. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction", section on 'Utilization'.)
In a 2005 United States nationwide study, unilateral or bilateral oophorectomy performed at the time of abdominal, laparoscopic, and vaginal hysterectomy occurred in 68, 60, and 26 percent of patients, respectively; the mean age of patients was between 44 and 49 years . In a subsequent study including over 190,000 hysterectomies for benign indication between 2005 and 2011 in California, concomitant oophorectomy was performed in 30 percent of patients . While rates of oophorectomy decreased over time (2005: 12,227 patients; 2011: 5930 patients), the percentage of oophorectomies with no reason for removal disproportionately remained stable (38 percent), with significant racial disparities appreciated.
Data from the Mayo Clinic Cohort Study of Oophorectomy and Aging (MOA) also confirm decreasing rates of bilateral oophorectomy at time of hysterectomy; from 2000 to 2018 rates decreased from 18 to 2.5 percent .
Role of estrogen therapy after hysterectomy with oophorectomy — Patients with premature (<40 years) or early (40 to 45 years) menopause due to bilateral oophorectomy are different from those who reach natural menopause (median age of 51 years), and data regarding the use of hormone therapy in naturally menopausal patients should not be extrapolated to those with surgical menopause [88-91].
In our practice, for patients with surgical menopause, we prescribe either transdermal estradiol (100 mcg daily) or an estradiol vaginal ring (100 mcg daily), which is roughly equivalent to 2 mg daily of oral micronized estradiol and based on the average daily production of estradiol by the premenopausal ovary. These doses are higher than those recommended for postmenopausal patients and are similar to the doses recommended for patients with premature ovarian insufficiency. A progestogen for endometrial protection is not needed. While androgen therapy may be used for selected patients with sexual dysfunction, the routine use of androgen therapy in this population is not well established, and long-term safety data are lacking . (See "Treatment of menopausal symptoms with hormone therapy", section on 'Surgical menopause' and "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy' and "Treatment of menopausal symptoms with hormone therapy", section on 'Routine use of testosterone therapy'.)
Data from the Women's Health Initiative (WHI) randomized trials are informative, and use of conjugated equine estrogen (CEE) alone is not associated with the risks seen in users of CEE plus progestin therapy . In the WHI Estrogen-Alone Trial, patients ages 50 to 79 with prior hysterectomy were assigned to CEE or placebo for a median of 7.2 years . While the overall benefits and risks of CEE were similar for patients with and without bilateral salpingo-oophorectomy (BSO), the risk of all-cause mortality was lower for those between the ages of 50 and 59 who had BSO and were treated with CEE (hazard ratio [HR] 0.68, 95% CI 0.48-0.96). All-cause mortality was similar in other age groups. This differential effect based on patient age at the initiation of hormone use is referred to as the "timing effect" and highlights the need for individualized care when discussing initiation of hormone therapy with patients who have had elective oophorectomy. Observational data also consistently indicate that some of the long-term health consequences of bilateral oophorectomy can be ameliorated with estrogen therapy until at least 60 years of age [13,35,38,42,60]. (See "Menopausal hormone therapy: Benefits and risks", section on 'Estimates of risk in women 50 to 59 years' and "Menopausal hormone therapy and cardiovascular risk", section on 'Timing of exposure'.)
Discussions of hormone therapy types, initiation, and duration of use are presented in detail separately. (See "Preparations for menopausal hormone therapy" and "Treatment of menopausal symptoms with hormone therapy".)
Surgical alternatives to oophorectomy for ovarian cancer risk reduction — For patients at average risk for ovarian cancer, other surgical procedures (ie, complete salpingectomy, tubal ligation, hysterectomy alone) provide an alternative to oophorectomy for ovarian cancer risk reduction without inducing surgical menopause.
Procedures that interrupt or remove the fallopian tubes have consistently been shown to reduce the risk of ovarian cancer [95-103]. This is discussed in detail separately. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction".)
Hysterectomy alone also reduces the risk of developing ovarian cancer. In a meta-analysis of 12 case-control studies, hysterectomy alone was associated with a 34 percent reduction in the risk of ovarian cancer [104,105].
While hysterectomy alone does not result in surgical menopause, it does appear to alter ovarian function, even if the ovaries are conserved. This effect is incompletely understood but may be due to impairment of the ovarian blood supply [106-108]. Observational studies have found that patients who undergo hysterectomy develop menopausal symptoms and changes in hormone profiles earlier than patients who do not undergo hysterectomy. In a prospective cohort study including over 500 premenopausal patients, those who had a hysterectomy (both ovaries retained) compared with those who did not have a hysterectomy reached menopause earlier (3.7 years, 95% CI 1.5–6 years); menopause was defined as a single FSH measurement of ≥40 international units/L . Furthermore, among all patients who underwent hysterectomy, those who had one ovary conserved compared with both ovaries conserved reached menopause 4.4 years earlier (95% CI 0.6-7.9 years).
The role of salpingectomy on ovarian blood supply and hormonal function is discussed separately.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic surgery".)
SUMMARY AND RECOMMENDATIONS
●Terminology – Elective oophorectomy refers to the removal of the ovaries in a patient who has no known indication for this procedure (eg, ovarian pathology, hereditary ovarian cancer syndrome). Other terms (eg, opportunistic, concurrent, incidental) may also be used. By contrast, risk-reducing salpingo-oophorectomy refers to the removal of the tubes and ovaries in a patient at high risk of ovarian or breast cancer due to a known gene mutation; these patients are discussed separately. (See 'Terminology' above and "Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer".)
•Bilateral oophorectomy reduces, but does not eliminate, the risk of developing ovarian cancer. Removal of the fallopian tubes provides additional risk reduction and there is an abundance of data demonstrating that the fallopian tubes, rather than the ovaries, are the primary site of most epithelial, fallopian tube, and peritoneal carcinomas (EOC). (See 'Ovarian cancer risk reduction' above and "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction".)
•Bilateral oophorectomy reduces the risk of breast cancer, although the age at which this benefit occurs is uncertain. While some data suggest that the risk reduction occurs only in patients with oophorectomy at <47.5 years, other data suggest that risk reduction may extend to age 60 years. (See 'Breast cancer risk reduction' above.)
●Long-term health risks – Oophorectomy is associated with an increase in the following; estrogen therapy may mitigate some of these risks (see 'Long-term health risks' above):
•Cardiovascular disease and stroke
•Chronic kidney disease
•Cognitive function and neurologic disease
•Depression and anxiety
●How to choose
•For most premenopausal patients who undergo hysterectomy for benign indications, we suggest ovarian conservation rather than elective oophorectomy (Grade 2C). While bilateral oophorectomy provides a small absolute cancer risk reduction for patients at an average risk of ovarian or breast cancer, it is associated with long-term health consequences. Patients with other pelvic pathology (eg, endometriosis, pelvic pain) may reasonably choose oophorectomy. (See 'Menopausal status' above.)
•For menopausal patients, elective bilateral oophorectomy may be health neutral. Oophorectomy is reasonable for patients who are 51 years of age or older who place a high priority on ovarian or breast cancer prevention. (See 'Menopausal status' above.)
•Oophorectomy may also be performed in patients with risk factors for ovarian cancer, but who do not have, or have not been tested for, a hereditary cancer syndrome. The decision regarding oophorectomy in such patients is more difficult and counseling should include a full discussion of the advantages and disadvantages of elective oophorectomy. (See 'Ovarian cancer risk factors' above.)
●Role of estrogen therapy – For premenopausal patients undergoing hysterectomy with concomitant oophorectomy resulting in surgical menopause, we suggest estrogen therapy (Grade 2C). The dose required for these patients is higher than that used for patients >50 years; we prescribe either transdermal estradiol (100 mcg daily) or an estradiol vaginal ring (100 mcg daily) and typically continue therapy until at least age 60 years. (See 'Role of estrogen therapy after hysterectomy with oophorectomy' above.)
●Alternatives to oophorectomy – For patients at average risk for ovarian cancer, other surgical procedures (ie, complete salpingectomy, tubal ligation, hysterectomy alone) provide an alternative to oophorectomy for ovarian cancer risk reduction without inducing surgical menopause. (See 'Surgical alternatives to oophorectomy for ovarian cancer risk reduction' above.)
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