Impact of hormone replacement therapy on the histologic subtype of breast cancer

OBJECTIVE: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer. PATIENTS AND METHODS: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for > or =6 months. RESULTS: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). CONCLUSIONS: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cancer.     

Self-reported bladder function five years post-hysterectomy.

We have examined the contribution of hysterectomy, compared with less invasive surgery, for dysfunctional uterine bleeding (DUB) on the prevalence of bladder problems five years after surgery. We report a prospective cohort study of over 25,000 women treated for benign cause menorrhagia by three types of surgery - transcervical endometrial resection/ablation and hysterectomy with or without bilateral oophorectomy. Postal questionnaires were sent five years after surgery investigating satisfaction with surgery and bladder function. When adjusted for confounders the odds of severe urinary incontinence (OR = 1.59, CI 95%, 1.35 - 1.87), urinary frequency (1.23 (1.04 - 1.45)), and nocturia (1.19, (1.03 - 1.38)) - were increased for women who had a hysterectomy compared with endometrial ablation. Hysterectomy with bilateral oophorectomy was not as strongly associated with severe bladder problems. Women who had the LAVH were most likely to report severe urinary incontinence (2.02, CI 95% 1.32 - 3.07), but not severe frequency or nocturia.     

Increased risk of thyroid cancer among women with hysterectomies

OBJECTIVE: Hysterectomy with bilateral oophorectomy has been suggested to increase the risk of thyroid cancer. We studied the relationship between hysterectomy and thyroid cancer in a population-based setting in Finland.Study Design: Women undergoing hysterectomy between 1986 and 1995 (n = 17,900) were identified from the National Hospital Discharge Registry. The cohort was followed up through the Finnish Cancer Registry until 1997. RESULTS: There were 118 cases of thyroid cancer diagnosed, 103 papillary and 15 follicular or medullar type. The incidence for thyroid cancer was significantly elevated (standardized incidence ratio [SIR] 1.38, 95% CI 1.15-1.64). The increase in the incidence of thyroid cancer was not dependent on the extent of operation but on the length of follow-up. Thyroid cancer incidence was increased 0.5 to 1.4 years after hysterectomy (SIR 2.00, 95% CI 1.31-2.93), but decreased thereafter (SIR 1.30, 95% CI 0.99-1.67). Hysterectomy with and without oophorectomy was associated with a similar increase in the incidence of thyroid cancer. CONCLUSION: Women who have undergone hysterectomy have an increased risk of thyroid cancer during the first 2 years after the operation. Thyroid cancer and bleeding disorders may share a common background.     

Factors affecting prophylactic oophorectomy in postmenopausal women

OBJECTIVE: Prophylactic oophorectomy performed concomitantly with hysterectomy may prevent ovarian cancer. Our goal was to better understand the basis for performing concomitant oophorectomy and to determine whether this procedure is associated with increased morbidity. METHODS: Our cross-sectional study used a hospital discharge database to identify women 50 years and older who, between 1994-1996, had hysterectomies in Maryland for a benign condition. We used multiple logistic regression to examine the independent effect of physician and patient factors on the likelihood of receiving a concomitant oophorectomy. RESULTS: Concomitant oophorectomy was performed in 61% of the 6227 women in our sample. Patients undergoing total abdominal hysterectomy (odds ratio [OR] 11.42; 95% confidence interval [CI] 9.65, 13.51) and laparoscopically assisted vaginal hysterectomy (OR 11.34; 95% CI 8.13, 15.81) were substantially more likely to have an oophorectomy than patients treated with vaginal hysterectomy, after adjusting for diagnosis and other covariates. We also found significant variation in the likelihood of receiving oophorectomy for women undergoing vaginal hysterectomy in different geographic regions. Additionally, physicians who performed many vaginal hysterectomies were significantly more likely to perform a concomitant oophorectomy. After adjusting for type of procedure, diagnosis, comorbidities, and age, oophorectomy was not associated with increased surgical morbidity. CONCLUSION: These results suggest that there are marked variations in physician practice style for concomitant oophorectomy. The variation across geographic regions and with case volume suggests the influence of nonclinical factors on oophorectomy rates.     

FSH levels in relation to hysterectomy and to unilateral oophorectomy

OBJECTIVE: To examine the association between hysterectomy, unilateral oophorectomy, and ovarian status, measured by FSH concentrations, in women aged 35-49 years. METHODS: From the National Health and Examination Survey III, 1716 women aged 35-49 years were studied. Information on menopausal status, surgical history (hysterectomy, single or bilateral oophorectomy), smoking, and other characteristics was collected in a structured interview, height and weight were measured, and one blood sample was collected. We used logistic regression to analyze FSH concentration in relation to hysterectomy and oophorectomy, controlling for age, ethnicity, body mass index, smoking, education, nulligravidity, and exercise. RESULTS: Hysterectomy with unilateral oophorectomy was associated with an increased prevalence of elevated FSH (above 20 IU/L) (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3, 4.6) compared with women who had not had hysterectomies or oophorectomies. Among women with two ovaries, hysterectomy was associated with increased prevalence of elevated FSH (adjusted OR 1.5, 95% CI 1.0, 2.5). As a comparison of the effect size, the observed association between hysterectomy and elevated FSH was smaller than the association between FSH and current smoking (OR 2.0), a factor associated with a 1-2 year decrease in mean age at natural menopause. CONCLUSION: Although the differences in FSH levels were small, there was evidence of elevated FSH in women who have had hysterectomies, even if at least one ovary remained.     

Bilateral Oophorectomy versus Ovarian Conservation: Effects on Long-term Women's Health

Bilateral oophorectomy at the time of hysterectomy for benign disease is commonly practiced to prevent the subsequent development of ovarian cancer. Currently, bilateral oophorectomy is performed in 55% of all U.S. women having a hysterectomy, with approximately 300 000 prophylactic oophorectomies performed every year. Observational studies show that estrogen deficiency, resulting from premenopausal or postmenopausal oophorectomy, is associated with higher risks of coronary artery disease, stroke, hip fracture, Parkinsonism, dementia, cognitive impairment, depression, and anxiety. These studies suggest that bilateral oophorectomy may do more harm than good. In women not at high risk for development of ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution.     

Role of prophylactic hysterectomy in patients at high risk for hereditary cancers

BACKGROUND: Current surgical recommendations for ovarian cancer prophylaxis in women at high risk of developing ovarian cancer include bilateral salpingo-oophorectomy (risk-reducing salpingo-oophorectomy (RRSO)). The role of hysterectomy is unclear. We sought to determine outcomes following prophylactic surgery in high-risk women. METHODS: We surveyed unaffected members of the Gilda Radner Familial Ovarian Cancer Registry who had undergone oophorectomy from 1981 to 2002. Data were collected and analyzed for statistical significance by the Fisher's Exact Test. RESULTS: Two hundred eighty women were surveyed, and 154 (55%) responded; 97% were Caucasian and 14% reported being Jewish. The median age of the respondents was 51 years (range 29-79); median age at oophorectomy was 41 years (range 15-68). Fifty-eight patients (38%) reported a laparoscopic procedure. One hundred five patients (68%) had a simultaneous hysterectomy, and 4 (3%) had a prior hysterectomy. Forty-four patients (29%) underwent BSO only. Of these 44 patients, 40 (91%) did not require a subsequent hysterectomy. Of the 4 who did, 2 were for leiomyomas, one for menorrhagia and the other was unknown. While not statistically significant, of the 3 patients who developed a subsequent gynecologic malignancy, all had undergone a hysterectomy. There was a statistically significant difference in whether or not the uterus was removed as part of the procedure by time period, whereby women treated prior to 1990 had a higher likelihood of having a hysterectomy (P = 0.03). CONCLUSION: The women in our study did not require hysterectomy for prevention of malignancy. We conclude that one should screen for benign gynecological indications for hysterectomy when planning a prophylactic BSO for prevention of ovarian cancer. Other potential risk factors for endometrial cancer, including the role of UPSC in HBOC, remain to be elucidated.     

Laparoscopic oophorectomy either with or without hysterectomy for early breast cancer

OBJECTIVES: The aim of this study was to assess the surgical results, complications and pathological findings of laparoscopic ovarian ablation either with or without hysterectomy in women with early-stage breast cancer (BC). METHODS: Ninety women in early breast cancer stage who underwent laparoscopic bilateral salpingo-oophorectomy (BSO) either with or without hysterectomy were identified in a retrospective study conducted between January 2000 and December 2006. Tamoxifen antiestrogen therapy was used prior to hysterectomy. RESULTS: Forty-eight consecutive patients underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy and 42 with ovarian ablation only. The mean operative time for the laparoscopic hysterectomy and bilateral salpingo-oophorectomy or BSO alone was 82 min and 47.8 min, respectively. Blood loss was minimal in both groups (range: 20-250 ml). The rate of postoperative complications was very low (4.4%). One of all ovaries removed by laparoscopy showed ovarian breast carcinoma metastasis. Histopathologic examination revealed concomitant findings of leiomyoma, adenomyosis or endometrial abnormalities in 64.5% of hysterectomy specimens. CONCLUSION: Our experience with ovarian ablation either with or without hysterectomy confirmed that the use of a minimally invasive technique is feasible. We assume that ovarian ablation and hysterectomy is an appropriate treatment for premenopausal women at risk (BRCA positive) or for patients with concomitant benign uterine pathology, treated with tamoxifen in first-line therapy. Removing the uterus allows women to take only estrogens rather than combination HRT. Further investigation into the indications of disease where laparoscopic ablative surgery is appropriate in the management of early breast cancer is needed.     

Prophylactic oophorectomy in women at increased cancer risk

PURPOSE OF REVIEW: Bilateral prophylactic salpingo-oophorectomy is widely used for cancer risk reduction in women with BRCA1/2 mutations. Bilateral prophylactic salpingo-oophorectomy significantly reduces breast cancer risk by approximately 50% and ovarian cancer risk by 80-95% but may be accompanied by menopausal symptoms, impaired quality of life and accelerated bone loss. Therefore, decisions regarding the timing of bilateral prophylactic salpingo-oophorectomy and the use of post-bilateral prophylactic salpingo-oophorectomy hormone replacement therapy must be carefully considered. RECENT FINDINGS: Over the last year, studies have further examined issues related to quality of life associated with bilateral prophylactic salpingo-oophorectomy and have demonstrated that hormone replacement therapy following bilateral prophylactic salpingo-oophorectomy in unaffected women does not negate the breast cancer risk reduction that bilateral prophylactic salpingo-oophorectomy provides. Studies have provided additional information on the residual risk of cancer following bilateral prophylactic salpingo-oophorectomy, have demonstrated its benefit in Lynch syndrome and have suggested a short-term mortality benefit following bilateral prophylactic salpingo-oophorectomy in BRCA1/2 mutation carriers. SUMMARY: We review the recent studies regarding bilateral prophylactic salpingo-oophorectomy and their implications for the clinical management of women who are at increased cancer risk.     

Ovarian conservation at the time of hysterectomy for benign disease

OBJECTIVE: Prophylactic oophorectomy is often recommended concurrent with hysterectomy for benign disease. The optimal age for this recommendation in women at average risk for ovarian cancer has not been determined. METHODS: Using published age-specific data for absolute and relative risk, both with and without oophorectomy, for ovarian cancer, coronary heart disease, hip fracture, breast cancer, and stroke, a Markov decision analysis model was used to estimate the optimal strategy for maximizing survival for women at average risk of ovarian cancer. For each 5-year age group from 40 to 80 years, 4 strategies were compared: ovarian conservation or oophorectomy, and use of estrogen therapy or nonuse. Outcomes, as proportion of women alive at age 80 years, were measured. Sensitivity analyses were performed, varying both relative and absolute risk estimates across the range of reported values. RESULTS: Ovarian conservation until age 65 benefits long-term survival for women undergoing hysterectomy for benign disease. Women with oophorectomy before age 55 have 8.58% excess mortality by age 80, and those with oophorectomy before age 59 have 3.92% excess mortality. There is sustained, but decreasing, benefit until the age of 75, when excess mortality for oophorectomy is less than 1%. These results were unchanged following multiple sensitivity analyses and were most sensitive to the risk of coronary heart disease. CONCLUSION: Ovarian conservation until at least age 65 benefits long-term survival for women at average risk of ovarian cancer when undergoing hysterectomy for benign disease.     

Oral contraceptives and epithelial ovarian cancer. Does dose matter?

OBJECTIVE: To determine the risk of ovarian cancer among women who use low-estrogen-dose oral contraceptives. STUDY DESIGN: The study used data on white women under 70 years of age who had been enrolled in a population-based case-control study conducted between 1986 and 1988 in three western Washington counties. Women with ovarian cancer (n = 276) were ascertained through a population-based cancer registry, and controls (n = 391) were selected by random digit dialing. Unconditional logistic regression was used to estimate the risk of ovarian cancer associated with oral contraceptive use. RESULTS: After adjustment for age and parity, women who took oral contraceptives for at least three months were at decreased risk of ovarian cancer (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.5-1.1) relative to women who never used this form of contraception. The reduced risk of ovarian cancer was present among women whose only preparation contained a low (< 50 micrograms ethinyl estradiol or < 80 micrograms mestranol) (OR 0.6, 95% CI 0.3-1.1) and high (OR 0.8, 95% CI 0.5-1.2) estrogen dose. CONCLUSION: While our results are limited in their statistical precision and by the inability of many subjects to recall the brands of oral contraceptives that they took, they suggest that the newer, low-estrogen-dose oral contraceptives confer a benefit regarding ovarian cancer risk similar to that conferred by earlier, high-estrogen-dose formulations.     

In vitro fertilization,endometriosis, nulliparity and ovarian cancer risk

ObjectivesTo examine the risk of invasive epithelial ovarian cancer in a cohort of women seeking treatment for infertility.MethodsUsing whole-population linked hospital and registry data, we conducted a cohort study of 21,646 women commencing hospital investigation and treatment for infertility in Western Australia in the years 1982–2002. We examined the effects of IVF treatment, endometriosis and parity on risk of ovarian cancer and explored potential confounding by tubal ligation, hysterectomy and unilateral oophorectomy/salpingo-oophorectomy (USO).ResultsParous women undergoing IVF had no observable increase in the rate of ovarian cancer (hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.35–2.90); the HR in women who had IVF and remained nulliparous was 1.76 (95% CI 0.74–4.16). Women diagnosed with endometriosis who remained nulliparous had a three-fold increase in the rate of ovarian cancer (HR 3.11; 95% CI 1.13–8.57); the HR in parous women was 1.52 (95% CI 0.34–6.75). In separate analyses, women who had a USO without hysterectomy had a four-fold increase in the rate of ovarian cancer (HR 4.23; 95% CI 1.30–13.77). Hysterectomy with or without USO appeared protective.ConclusionsThere is no evidence of an increased risk of ovarian cancer following IVF in women who give birth. There is some uncertainty regarding the effect of IVF in women who remain nulliparous. Parous women diagnosed with endometriosis may have a slightly increased risk of ovarian cancer; nulliparous women have a marked increase in risk.     

Predictors of urinary incontinence in a prospective cohort of postmenopausal women

OBJECTIVE: To prospectively assess risk factors associated with occurrence of urinary incontinence among postmenopausal women. METHODS: We followed up 1,017 postmenopausal health maintenance organization enrollees, aged 55 to 75 years, for 2 years. The primary outcome measures were any urinary incontinence and severe incontinence reported at 12- or 24-month follow-up visits. RESULTS: Baseline prevalence of any amount or frequency of urinary incontinence in the past year was 66%. Among the 345 women without incontinence at baseline, 65 (19%) at 1 year and 66 (19%) at 2 years reported any incontinence. Ninety-two of 672 (14%) and 96 of 672 (14%) women with incontinence at baseline reported no incontinence at years 1 and 2. In an adjusted multiple logistic regression model, independent predictors of any incontinence included white race (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6), vaginal estrogen cream (OR 2.0, CI 1.1-3.7), vaginal dryness (OR 1.6, CI 1.2-2.2), vaginal discharge (OR 1.5, CI 1.0-2.2), 6 or more lifetime urinary tract infections (OR 1.8, CI 1.2-2.6), and diabetic peripheral neuropathy (OR 1.7, CI 1.0-3.1). In adjusted models, predictors of severe incontinence were history of hysterectomy (OR 1.8, CI 1.1-2.7) and any vaginal symptom (OR 1.7, CI 1.0-2.8). CONCLUSION: A substantial proportion of incontinence-free postmenopausal women developed urinary incontinence during 2 years of follow-up. Because vaginal symptoms are associated with urinary incontinence, their relationship with other risk factors, including vaginal Escherichia coli colonization and vaginal estrogen cream use, warrant additional study. Similarly, diabetic peripheral neuropathy and hysterectomy associations suggest areas for future investigation. LEVEL OF EVIDENCE: II-2.     

Postmenopausal hormone therapy and risk of developing urinary incontinence

OBJECTIVE: To better understand associations between post-menopausal hormone therapy and the development of urinary incontinence. METHODS: Postmenopausal hormone use was assessed via biennial mailed questionnaires beginning in 1976 among Nurses' Health Study participants. In 1996, 39,436 post-menopausal women aged 50-75 years reported no leaking of urine and were followed-up for 4 years to identify incident cases of incontinence. We used logistic regression to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relation of postmenopausal hormone use from 1976 to 1996 to the development of incontinence from 1996 to 2000. RESULTS: We identified 5,060 incident cases of occasional (leaking urine 1-3 times/month) and 2,495 cases of frequent incontinence (leaking at least weekly) for average yearly incidence rates of 3.2% and 1.6%, respectively. The risk of incontinence was elevated among women taking postmenopausal hormones compared with women who had never taken hormones (oral estrogen: RR 1.54, 95% CI 1.44, 1.65; transdermal estrogen: RR 1.68, 95% CI 1.41, 2.00; oral estrogen with progestin: RR 1.34, 95% CI 1.24, 1.44; transdermal estrogen with progestin: RR 1.46, 95% CI 1.16, 1.84). There was little risk after the cessation of hormones (RR 1.14, 95% CI 1.06, 1.23) and a decreasing risk of incontinence with increasing time since last hormone use; 10 years after stopping hormones, the risk was identical in women who had and had never taken hormone therapy (RR 1.02, 95% CI 0.91, 1.14). CONCLUSION: Postmenopausal hormone therapy appears to increase risk of developing urinary incontinence. This risk does not vary by route of administration, type of hormones, or dose taken, but is diminished upon cessation of use. LEVEL OF EVIDENCE: II-2     

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.     

Retention of ovaries and oxidative stress of surgery.

OBJECTIVE: Surgical menopause results in severe menopausal symptoms due to the sudden withdrawal of estrogen. This study evaluated the impact of surgical menopause on oxidant and antioxidant status. METHODS: Thirty eight women who underwent total hysterectomy with or without bilateral salpingo-oophorectomy were included. Oxidant status was assessed by measuring plasma levels of malondialdehyde (MDA) and antioxidant status by assessing glutathione (GSH) and estrogen levels. RESULTS: The levels of MDA were increased in all women, and GSH levels were significantly decreased in women who underwent hysterectomy alone but significantly increased in those who also had oophorectomy. Estrogen levels were increased if the ovaries were retained even in postmenopausal women, while they were decreased in the women who underwent oophorectomy. CONCLUSION: Oxidative stress of surgery, as assessed by increased MDA levels, occurred in all women. After oophorectomy, estrogen levels decreased and GSH levels increased in both premenopausal and postmenopausal women. The ovaries may therefore respond to oxidative stress of surgery by increasing estrogen production, estrogen being a better antioxidant than GSH.     

Cesarean delivery and peripartum hysterectomy

OBJECTIVE: To estimate the national incidence of peripartum hysterectomy and quantify the risk associated with cesarean deliveries and other factors. METHODS: A population-based, matched case-control study using the United Kingdom Obstetric Surveillance System, including 318 women in the United Kingdom who underwent peripartum hysterectomy between February 2005 and February 2006 and 614 matched control women. RESULTS: The incidence of peripartum hysterectomy was 4.1 cases per 10,000 births (95% confidence interval [CI] 3.6-4.5). Maternal mortality was 0.6% (95% CI 0-1.5%). Previous cesarean delivery (odds ratio [OR] 3.52, 95% CI 2.35-5.26), maternal age over 35 years (OR 2.42, 95% CI 1.66-3.58), parity of three or greater (OR 2.30, 95% CI 1.26-4.18), previous manual placental removal (OR 12.5, 95% CI 1.17-133.0), previous myomectomy (OR 14.0, 95% CI 1.31-149.3), and twin pregnancy (OR 6.30, 95% CI 1.73-23.0) were all risk factors for peripartum hysterectomy. The risk associated with previous cesarean delivery was higher with increasing numbers of previous cesarean deliveries (OR 2.14 with one previous delivery [95% CI 1.37-3.33], 18.6 with two or more [95% CI 7.67-45.4]). Women undergoing a first cesarean delivery in the current pregnancy were also at increased risk (OR 7.13, 95% CI 3.71-13.7). CONCLUSION: Peripartum hysterectomy is strongly associated with previous cesarean delivery, and the risk rises with increasing number of previous cesarean deliveries, maternal age over 35 years, and parity greater than 3. LEVEL OF EVIDENCE: II.     

The association of hysterectomy and menopause: a prospective cohort study

OBJECTIVE: To determine whether or not hysterectomy leads to an earlier onset of the menopause. DESIGN: A prospective cohort study. SETTING: Gynaecology service of large urban hospital. POPULATION: Premenopausal women with and without hysterectomy. METHODS: Multivariate survival analysis techniques were used to adjust for differences in initial follicle stimulating hormone (FSH) levels, body mass index, smoking and unilateral oophorectomy between the groups. MAIN OUTCOME MEASURES: FSH levels were measured for five years following hysterectomy and compared with the comparison group. Menopause was defined as a single FSH measurement of at least 40 IU/L. RESULTS: Two hundred and fifty-seven women undergoing hysterectomy were compared with 259 women who had not undergone a hysterectomy. Fifty-three women (20.6%) in the hysterectomy group and 19 women (7.3%) in the comparison group reached menopause over the five years of the study. Women in the hysterectomy group with a pre-operative FSH <10 IU/L reached menopause 3.7 years (95% CI 1.5-6.0 years) earlier than women in the comparison group independent of BMI, smoking and unilateral oophorectomy. Twenty-eight women in the hysterectomy group had unilateral oophorectomy and 10 (35.7%) of these women reached menopause over the five years of follow up. Women in the hysterectomy group with unilateral oophorectomy reached menopause 4.4 years (95% CI 0.6, 7.9 years) earlier than women with both ovaries in the hysterectomy group independent of baseline FSH, BMI and smoking. CONCLUSIONS: Hysterectomy is associated with an earlier onset of menopause. Hysterectomy with unilateral oophorectomy is associated with an even earlier onset of the menopause in this study.     

Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer

OBJECTIVE: To analyze the role of hysterectomy, performed on benign indications, on the risk of developing ovarian cancer. METHODS: Multicenter case-control study conducted in four Italian areas. Cases were 1031 women with epithelial ovarian cancer. Controls were 2411 women admitted to the same network of hospitals for a wide spectrum of acute non-neoplastic conditions, unrelated to known risk factors for ovarian cancer. RESULTS: Compared to women with intact uterus and ovaries, the multivariate odds ratios (OR) was 0.6 (95% confidence interval 0.4-0.9) for women who reported hysterectomy. The OR was 0.5 > or =15 years after surgery. The OR was similar for women who had had pelvic surgery before age 45 and for those who had surgery later. No appreciable heterogeneity emerged across strata of parity and family history of ovarian/breast cancer. CONCLUSION: Women who had undergone hysterectomy had a long-term reduced risk of epithelial ovarian cancer.