A prospective study of 3 years of outcomes after hysterectomy with and without oophorectomy

American Journal of Obstetrics and Gynecology (2006) 194, 711 7 www.ajog.org A prospective study of 3 years of outcomes after hysterectomy with and without oophorectomy Cynthia M. Farquhar, MBChB, FRANZCOG, MD, CREI, MPH, a,b Sally A. Harvey, RN, RMidwife, a Yi Yu, MSc, a Lynn Sadler, MBChB, MRANZCOG, MPH, a,b Alistair W. Stewart, BSc b Department of Obstetrics and Gynecology, National Women s Hospital a and School of Population Health, b University of Auckland, Auckland, New Zealand Received for publication June 20, 2005; revised August 4, 2005; accepted August 24, 2005 KEY WORDS Hysterectomy Oophorectomy Patient satisfaction Objective: This study was undertaken to determine the outcomes of hysterectomy with and without conservation of the ovaries. Study design: Data were collected prospectively for 3 years from 257 women undergoing hysterectomy (group 1) and 57 women undergoing hysterectomy with oophorectomy (group 2). Results: Pelvic pain, abdominal pain, and depression scores were reduced in the 3 years after hysterectomy. Twenty-one percent of the women in group 1 and 43% in group 2 regretted the loss of fertility 3 years after hysterectomy. Satisfaction with the operation was greater than 90% after 3 years in both groups. New symptoms of pelvic pain were infrequent in groups 1 (3%) and 2 (5%). Conclusion: Three years after undergoing hysterectomy with and without oophorectomy, satisfaction is high although some women regret the loss of fertility. Ó 2006 Mosby, Inc. All rights reserved. Hysterectomy is one of the most commonly performed surgical procedures. In the United States 25% of women undergo hysterectomy by the age of 60 years. 1 The extensive use of hysterectomy in women without disease has lead to discussions of the merits of the procedure. 2 Although there are many reports suggesting hysterectomy results in positive outcomes, long-term prospectively collected data after hysterectomy are infrequently reported. The more obvious positive outcomes Support provided by Lottery Grants Board, New Zealand, Health Research Council of New Zealand, Mercia Barnes Trust of the Royal Australian, and New Zealand College of Obstetricians and Gynaecologists. Reprints not available from the authors. relate to the cessation of abnormal uterine bleeding and relief from monthly menstrual symptoms. 3 Other symptoms reported to improve include pelvic pain caused by endometriosis, pressure symptoms associated with fibroids, urinary incontinence, sexual function, and depression and anxiety, 4-8 and high satisfaction rates with hysterectomy are consistently reported. 2,9,10 However, not all women experience relief of symptoms after hysterectomy and a small proportion of women subsequently have new symptoms develop. 4,6 Hysterectomy has been implicated in the development of new urinary and lower gastrointestinal symptoms and a decline in sexual functioning. 11,12 Other concerns include loss of childbearing capacity, weight gain, change in self-image, social and domestic disruptions, 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.08.066

712 Farquhar et al long recovery times, and wound pain up to a year after surgery. 3,12 The role of oophorectomy in association with hysterectomy is controversial. Many premenopausal women undergo this procedure 1,6 and clinical guidelines for prophylactic oophorectomy have been published. 13 The reasons behind the recommendation for oophorectomy at the time of hysterectomy include improved outcomes for women with pelvic pain, endometriosis, and premenstrual symptoms. 14-16 In older premenopausal women, the decision to have an oophorectomy may arise because of concerns about ovarian cancer risk. However, there are concerns that oophorectomy, in fact, may lead to new health problems, and a recently published decision analysis suggests no improvement in long-term survival for women undergoing oophorectomy. 17 The aim of this study was to determine prospectively the physical and psychologic effects of hysterectomy with and without conservation of the ovaries for 3 years. Methods This prospective cohort study was commenced in December 1994. Recruitment was completed at the end of 1997. Ethical approval was obtained from the local Health Funding Authority ethical committee for each year of the study and written informed consent was obtained from all participants. Women younger than 46 years were recruited: Group 1 included women who underwent hysterectomy with conservation of at least 1 ovary and Group 2 included women who underwent hysterectomy and bilateral oophorectomy. All women in Group 2 were offered estrogen replacement therapy following surgery. An additional group (Group 3) of women who had not undergone hysterectomy and were on no hormonal contraception has also been recruited. The results comparing groups 1 and 3 have been presented in a separate publication. 18 Women on the surgical waiting list received written information about hysterectomy and a letter of invitation to participate in the study. Women with malignancy of the cervix, endometrium, or ovary were excluded. One week before surgery a questionnaire was completed by each participant. Information was collected on reproductive history, reasons for hysterectomy, gynecologic symptoms, urinary and bowel symptoms, sexuality, general health and well-being, and concerns about the effects of hysterectomy. The questionnaire had been piloted with 20 women before the study commenced. Some changes were made to the questionnaire as the result of the piloting. A follicle-stimulating hormone (FSH) level (early follicular phase) was measured and women with a FSH R40 mmol/l were excluded from the study. During the hospital admission data were collected on the operative procedure and early postoperative complications. A questionnaire was sent to the participants at 6 weeks and 6 months after the hysterectomy and then annually for 3 years. The questionnaire encompassed aspects of postoperative recovery, satisfaction with the operation, gynecologic, urinary, and bowel symptoms, sexual activity and frequency, and regrets. Questions were asked on a 5-point scale from never to sometimes to often and have been condensed to categories of no (for never ) or yes (includes any response other than never ) as given in the tables. Dissatisfaction was defined as very dissatisfied or dissatisfied. The 6 week and 6 month data, including early complications have been previously reported. 19 The Center for Epidemiologic Studies Depression scale (CES-D) was administered at the outset of the study and at each follow-up. 20 A score of 16 or higher (range 0-60) was used to define depression. Women in Group 1 had annual FSH levels, and if FSH levels were R 40 IU/L and if they were symptomatic, the estrogen replacement therapy was offered. The data on FSH levels have been previously published. Statistical methods Power calculations have been previously reported. 19 The simple comparisons of baseline frequency data between the 2 groups were made by testing for independence in 2!K contingency tables. As the women in this study have been monitored for 3 years with a questionnaire each year, there are 4 measures of each variable for each women. These repeated measures data have been analyzed with the use of a linear mixed model. This model allows for the correlation between times within women using an autoregressive correlation structure. The outcome measures are all recorded as either yes or no and so a logistic regression model was used. From the 4 measures, 2 contrasts of interest have been examined. The first was the effect of the operation, comparing the prehysterectomy response with the responses at any of the 1-, 2-, or 3-year follow-up questionnaires after the hysterectomy and the second was to see if there was a change in response over the 3 years of follow-up. Group 2 was analyzed separately from group 1. It has been assumed that the disappearance of the women lost to follow-up is not associated with the outcomes analyzed. Statistical analyses were performed with SAS version 9.1 (Cary, NC). Results Two hundred fifty-seven women were recruited to Group 1 and 57 to Group 2. The losses to follow-up and withdrawals are given in the Figure. The demography, reasons for hysterectomy, the method of hysterectomy, and the histologic results reported for groups 1 and 2 are presented in Table I.

Farquhar et al 713 Figure Follow-up of Group 1 and 2 participants. Number in brackets is missing data for that time period. FU, Follow up. A statistically significant reduction in pelvic pain, abdominal pain, and depression scores were reported from before hysterectomy to after hysterectomy (1 to 3 years of follow-up), but there were no changes within the 3 years after the hysterectomy in either group (Table II). No changes were reported in the proportion of sexual active women over the 3 years of the study in either group (Table II). Urinary frequency was

714 Farquhar et al Table I Demographics and operation details for groups 1 and 2 Group 1 (n = 257) Group 2 (n = 57) P value Age (y) %30 12 (5%) 3 (5%) 31-35 41 (16%) 14 (25%) 36-40 87 (34%) 16 (28%) 41-45 117 (45%) 24 (42%).5 Ethnicity New Zealander 202 (79%) 35 (61%) NZ Maori 36 (14%) 4 (7%) Other 19 (7%) 6 (11%).3 Current smoker 84 (33%) 21 (38%).8 Nulliparous 17 (6%) 17 (30%).001 BMI* %19 8 (4%) 1 (2%) 19%BMI%26 110 (43%) 25 (45%) O26 136 (53%) 30 (53%).8 FSH prerecruitment 4.8 (3.4-7.5) 5.0 (3.2-7.6).8 Reasons for hysterectomy Heavy menstrual 207 (80) 36 (63).001 bleeding Pelvic pain, including 15 (6) 10 (18) endometriosis, infection, or adhesions Fibroids 11 (4) 1 (2) Dysmenorrhoea 9 (4) 7 (12) Uterovaginal prolapse/ 9 (4) 3 5 stress incontinence/ other Abnormal cervical 6 (2) 0 0 smear/histology Type of hysterectomy Abdominal 92 (36) 42 (74)!.001 Vaginal 128 (50) 8 (14) Laparoscopic 37 (14) 7 (12) Subtotal 3 (1) 3 (5) Unilateral 26 (10) 7 (12) y oophorectomy Histopathology Fibroids 107 (42) 19 (35).369 Adenomyosis 39 (16) 10 (19).503 Endometrial hyperpasia 5 (2) 0.406 Endometrial polyps 11 (4) 6 (12).045 Ovarian cysts zx 18 (7) 33 (58)!.001 Data are n (%) or median (interquartile range). BMI, Body mass index; NZ, New Zealand. * BMI = kg/m 2. y Seven women in Group 2 previously had 1 ovary removed. z In Group 1, ovarian cysts included follicular or luteal cysts (n = 14 women), endometrioma (n = 6), polycystic ovaries (n = 1), mucinous cystadenoma (n = 1), mucinous epithelial cyst (n = 1), dermoid cyst (n = 1), and a theca lutein cyst (n = 1). x In Group 2 ovarian cysts included follicular or luteal cysts (n = 22 women), endometrioma (n = 13), polycystic ovaries (n = 7), dermoids (n = 1), serous cystadenomas (n = 2), epithelial inclusion cysts (n = 2), paraovarian cysts (n = 2), and a granulosa lutein cyst (n = 1). significantly reduced over the 3 years of follow-up in both groups (Table II). Regret and satisfaction data are presented in Table III. Among the women who had pelvic pain before surgery, 24% from Group 1 and 36% from Group 2 were still experiencing pain 3 years after surgery. Among the women who had no pelvic pain before surgery only 1 in 34 (3%) in Group 1 and only 1 in 5 in Group 2 had new symptoms of pain 3 years after hysterectomy. Among the women who had a CES-D score R16 before surgery, 34 of 64 (53%) of Group 1 (36 women did not complete the 3-year follow-up) and 11 of 27 (41%) of women from Group 2 (9 women did not complete the 3-year follow-up) had a score less than 16 after 3 years. Among the women who had depression scores less than 16 before surgery, 18 of 103 (17%) in Group 1 and 6 of 16 (38%) in Group 2 subsequently had scores R16. All 22 women in Group 1 with FSH levels R40 IU/L during 3 years of follow-up reported that they were satisfied with the operation and 5 (23%) had CES-D scores R16. Comment This study reports prospective data preoperatively and up to 3 years after surgery on a cohort of women who have had hysterectomy with and without conservation of the ovaries. Although the women in the 2 groups were similar in age, ethnicity, and smoking behavior, there are differences between the 2 groups, which are likely to influence the outcomes studied. Most notably, the women in Group 2 were more often nulliparous, more likely to have an abdominal hysterectomy, more likely to have preexisting bowel symptoms, pelvic, and abdominal pain, and to have depression scores R16 than the women in Group 1. If the aim of the hysterectomy is to relieve abdominal and pelvic pain, then for two thirds of women with pain this has been achieved, both with and without oophorectomy. The long-term management of pelvic pain is an infrequent topic for research. A prospective study of 36 women who attended a research pain clinic with chronic pelvic pain who were monitored for 1 year after hysterectomy and bilateral oophorectomy, 33% reported that they had some residual pain, although only 1 woman still had pain that was affecting daily functioning. 14 A larger study of 400 women with pain monitored for 24 months after hysterectomy with conservation of the ovaries also reported considerable relief from pain. 21 The results from our study are consistent with those studies for women undergoing hysterectomy with and without oophorectomy. Our study also reported improvements in depression scores after hysterectomy in both groups. Almost 50% of women in Group 1 and more than 60% of women in

Farquhar et al 715 Table II Clinical symptoms, depression scores, and sexual function before hysterectomy and at 1, 2, and 3 y posthysterectomy: Groups 1 and 2 N = 257/57 1y N = 219/50 2y N = 206/46 3y N = 196/46 vs post (P) Pelvic pain Gp 1 79% 26% 24% 20%.000.328 Gp 2 85% 46% 36% 33%.000.472 Abdominal pain Gp 1 48% 31% 29% 34%.000.485 Gp 2 68% 46% 52% 46%.009.713 Hot flushes Gp 1 31% 18% 24% 29%.035.011 Gp 2 47% 42% 47% 48%.868.728 Vaginal dryness Gp 1 26% 22% 29% 28%.428.038 Gp 2 26% 34% 46% 35%.116.263 CES-D score R16 Gp 1 43% 24% 26% 27%.000.713 Gp 2 67% 45% 56% 50%.042.730 Sexually active Gp 1 82% 85% 87% 87%.146.764 Gp 2 67% 66% 70% 71%.725.930 Sex R2/mo Gp 1 70% 85% 82% 81%.000.672 Gp 2 55% 69% 58% 66%.338.237 Urinary frequency Gp 1 43% 26% 26% 26%.000.807 Gp 2 53% 42% 33% 30%.013.446 Nocturia Gp 1 36% 24% 26% 23%.000.621 Gp 2 44% 40% 46% 39%.394.775 Urge incontinence Gp 1 32% 25% 31% 32%.473.045 Gp 2 41% 38% 37% 46%.779.198 Stress incontinence Gp 1 48% 43% 43% 43%.153.818 Gp 2 47% 38% 50% 57%.894.080 Difficulty urinating Gp 1 9% 7% 4% 5%.104.253 Gp 2 12% 8% 4% 13%.628.035 Sensation of residual urine Gp 1 34% 27% 29% 30%.168.389 Gp 2 43% 46% 28% 39%.258.013 Constipation Gp 1 36% 21% 21% 26%.000.415 Gp 2 27% 24% 26% 24%.772.945 Diarrhea Gp 1 28% 16% 12% 16%.000.268 Gp 2 40% 20% 30% 26%.023.259 Alternating bowel habit Gp 1 16% 14% 12% 16%.387.361 Gp 2 10% 12% 24% 13%.296.106 Bloating Gp 1 36% 34% 39% 41%.658.162 Gp 2 55% 38% 41% 50%.121.211 Gp, Group; CES-D, Center for Epidemiologic Studies-Depression; N, number of women in group 1/number of women in group 2. Change over y 1-3 (P)

716 Farquhar et al Table III Health status, satisfaction and regrets at 1, 2, and 3 y posthysterectomy: Groups 1 and 2 N = 257/57 1y N = 219/50 2y N = 206/46 3y N = 196/46 vs post (P) Some regret at loss of periods Gp 1 2% 5% 3% 4%.055.421 Gp 2 5% 4% 7% 2%.645.551 Some regret at loss of fertility Gp 1 5% 26% 27% 21%.000.242 Gp 2 13% 42% 48% 43%.000.637 Some concerns regarding femininity Gp 1 13% 16% 12% 13%.723.468 Gp 2 36% 30% 33% 22%.155.341 Current health status is good or very good Gp 1 44% 64% 65% 64%.000.930 Gp 2 33% 58% 48% 54%.005.629 Satisfied with operation Gp 1 d 97% 94% 97% d.224 Gp 2 d 98% 91% 98% d.202 Gp, Group. Change over y 1-3 (P) Group 2 were depressed before surgery. Depression before major surgical interventions is not uncommon or unexpected and has been reported both before hysterectomy and cholecystectomy. 22 Women with menstrual problems have been reported to have higher levels of depression than the general population. 23 A communitybased study of more than 4000 women aged 36 to 44 years reported that 22% had CES-D scores of 16 that are very similar to the rates for women in Group 1 of our study. 24 Higher rates of depression were present before surgery in Group 2 and remained throughout the 3 years of follow-up. Group 2 women also had higher rates of regret at loss of fertility and loss of femininity and it is possible that these are related to the higher depression scores. These results are not new, although no other study identified that used CES-D scores to define depression included women with oophorectomy and had this length of follow-up. 4,8,9,23 Women often express a fear that hysterectomy will impact negatively on sexual functioning. A decline in sexual activity and satisfaction could theoretically result from changes in the anatomy at hysterectomy, from emotional changes or changes in hormone levels secondary to oophorectomy or ovarian failure. In our study there were preoperative differences in the levels of sexual activity between the 2 groups of women. This could be explained by the higher proportion of women undergoing hysterectomy for pain in Group 2. Over the 3 years of follow-up, there was no change in the proportion of women who were sexually active in either group compared with prehysterectomy, although sexual frequency increased significantly in Group 1. Previous reports, which were predominantly retrospective, are conflicting with no change, improvements, and declines in sexual activity all being reported. 4,7-10 New symptoms arising subsequent to hysterectomy have been reported previously in less than 10% of women. 6,23 In this study very few women undergoing hysterectomy had new symptoms of pelvic pain develop after 3 years. In an earlier article we reported new symptoms 6 months posthysterectomy in 16% of Group 1 and 37% in Group 2. 20 It is reassuring that these pain symptoms resolved with time. Of concern, 27% of Group 1 and 50% of Group 2 had depression develop in the 3 years after hysterectomy. In another large study of women with hysterectomy, less than 10% had depression (using a different depression scale) at 24 months. 23 Satisfaction with hysterectomy has consistently been reported as being high among women who undergo hysterectomy and our results do not differ in this respect. 4,6,10,11 It is interesting to reflect that although more than 90% of women in both groups were satisfied with the operation, 3 years after surgery, many were still experiencing symptoms and a proportion regretted the loss of fertility. These results suggest that further research is needed to detect the underlying value that a woman places on the procedure. In summary, we have reported data with 3 years follow-up from a prospective cohort of women who have either undergone hysterectomy or hysterectomy with bilateral oophorectomy. This report provides prospective and new information on the outcomes of

Farquhar et al 717 hysterectomy and oophorectomy 3 years posthysterectomy. Women considering hysterectomy should receive a full discussion of all possible outcomes, including regret. Acknowledgment We acknowledge Mrs Elizabeth Robinson of the Biostatistical Unit at the University of Auckland who advised on the early study design and analysis of the results. References 1. Keshavarz H, Hillis SD, Kieke BA, Marchbanks PA. Hysterectomy Surveillance-United States, 1994-1999. MMWR CDC Surveill Summ 2002;51:1-8. 2. Simkin S. Psychiatric and psychological aspects of hysterectomy. BMJ 1996;313:231. 3. Nathorst-Boos J, Fuchs T, Von Schoultz B. Consumer s attitude to hysterectomy: the experience of 678 women. Acta Obstet Gynecol Scand 1992;71:230-4. 4. Carlson KJ, Miller BA, Fowler FJ. The Maine Women s Health Study: outcomes of hysterectomy. Obstet Gynecol 1994;83:556-65. 5. Hillis SD, Marchbanks PA, Peterson HB. The effectiveness of hysterectomy for chronic pelvic pain. Obstet Gynecol 1995;86:941-5. 6. Kjerulff KH, Langenberg PW, Rhodes JC, Harvey LA, Guzinski GM, Stolley PD. Effectiveness of hysterectomy. Obstet Gynecol 2000;95:319-26. 7. Roovers JP, van der Bom JG, van der Vaart CH, Heintz AP. Hysterectomy and sexual wellbeing: prospective observational study of vaginal hysterectomy, subtotal abdominal hysterectomy, and total abdominal hysterectomy. BMJ 2003;327:774-8. 8. Alexander DA, Naji AA, Pinion SB, Mollison J, Kitchener HC, Parkin DE, et al. Randomized trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects. BMJ 1996;312:280-4. 9. Weber AM, Walters MD, Schover LR, Church JM, Peidmonte MR. Functional outcomes and satisfaction after abdominal hysterectomy. Am J Obstet Gynecol 1999;181:530-5. 10. Kjerulff KH, Rhodes JC, Langenberg PW, Harvey LA. Patient satisfaction with results of hysterectomy. Am J Obstet Gynecol 2003;183:1440-7. 11. Taylor T, Smith AN, Fultom PM. Effect of hysterectomy on bowel function. BMJ 1989;299:300-1. 12. Schofield MJ, Bennet A, Redman S, Walters WAW, Sanson-Fisher RW. Self reported long-term outcomes of hysterectomy. BJOG 1991;98:1129-36. 13. American College of Obstetrics and Gynecology. Prophylactic oophorectomy. Washington (DC): The College; 1999. ACOG Practice Bulletin no. 7. 14. Beard RW, Kennedy RG, Gangar KF, Stones RW, Rogers V, Reginald PW, et al. Bilateral oophorectomy and hysterectomy in the treatment of intractable pelvic pain associated with pelvic congestion. BJOG 1991;98:988-92. 15. Cronje WH, Vashisht A, Studd JW. Hysterectomy and bilateral oophorectomy for severe premenstrual syndrome. Hum Reprod 2004;19:2152-5. 16. Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL, Rock JA. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril 1995;64:898-902. 17. Parker W, Broder M, Liu Z, Shoupe D, Farquhar C, Berek J. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol 2005;106:219-26. 18. Farquhar CM, Sadler L, Harvey S, Stewart A. The association of hysterectomy and menopause: a prospective cohort study. BJOG 2005;112:956-62. 19. Farquhar CM, Sadler L, Harvey S, McDougall J, Yazdi G, Meuli K. A prospective study of the short term outcomes of hysterectomy with and without ovarian conservation. Aust N Z J Obstet Gynaecol 2002;42:197-204. 20. Radloff LS, Locke BZ. Center for epidemiologic studies for depression scale (CES-D). In: Handbook of psychiatric measures. Arlington (VA): American Psychiatric Association; 1999. p. 523-6. 21. Hartmann KE, Ma C, Lamvu GM, Langenberg PW, Steege JF, Kjerulff KH. Quality of life and sexual function after hysterectomy in women with preoperative pain and depression. Obstet Gynecol 2004;104:701-9. 22. Lalinec-Michaud M, Engelsmann F, Marino J. Depression after hysterectomy: a comparative study. Psychosomatics 1988; 29:307-14. 23. Gath D, Osborn M, Bungay G, Iles S, Day A, Bond A, et al. Psychiatric disorder and gynaecological symptoms in middle aged women: a community survey. BMJ (Clin ResEd) 1987;294: 213-8. 24. Harlow BL, Cohen LS, Otto MW, Spiegelman D, Cramer DW. Prevalence and predictors of depressive symptoms in older premenopausal women: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry 1999;56:418-24.