The Journal of International Medical Research 2007; 35: 416 421 Hysterectomy with Preservation of both Ovaries does not Result in Premature Ovarian Failure V ATAY 1, T CEYHAN 2, İ BASER 2, S GUNGOR 2, Ü GOKTOLGA 2 AND M MUHCU 1 1 Department of Obstetrics and Gynaecology, GATA Haydarpasa Training Hospital, Istanbul, Turkey; 2 Department of Obstetrics and Gynaecology, GATA Training Hospital, Ankara, Turkey This study investigated ovarian function and adnexial pathology following total abdominal hysterectomy with preservation of both ovaries compared with that in a control group. Data from 29 patients who had undergone total abdominal hysterectomy at age 40 years and 42 menopausal patients with no previous ovarian pathology were evaluated retrospectively. The mean (± SD) age of menopause was 49.7 ± 1.5 years in the total abdominal hysterectomy group and 50.1 ± 1.3 years in the control group; this difference was not statistically significant. The incidences of cyst and hydrosalpinx were 31% and 6.9%, respectively, in the total abdominal hysterectomy group and 44.8% and 0%, respectively, in the control group. The increased incidence of cysts in the total abdominal hysterectomy group was statistically significant. In conclusion, patients who undergo total abdominal hysterectomy without oophorectomy do not experience premature menopause. Preservation of the ovaries may avoid the disadvantages of hormone replacement therapy at the expense of a higher risk of developing adnexial pathology. KEY WORDS: HYSTERECTOMY; OOPHORECTOMY; MENOPAUSE; OVARIAN FUNCTION; ADNEXIAL PATHOLOGY; OVARIAN CYSTS; HYDROSALPINX Introduction The question as to whether normal ovaries should be removed or preserved during abdominal hysterectomy in pre-menopausal women has not yet been resolved. There is no consensus concerning the removal or conservation of the ovaries, nor whether there should be a cut-off age. 1 The main problem associated with conservation of the ovaries is that ovarian cancer may subsequently develop. 2 The risk of cancer development in the remaining ovaries, together with the difficulty in diagnosing this disease, has led to the practice in the UK and USA of oophorectomy being performed during hysterectomies in women > 40 years old. 3,4 Cessation of ovarian function is associated with an increased risk of osteoporosis and coronary artery disease. Other complaints, which are associated with lack of oestrogen production, include vasomotor hot flushes, urogenital, anal or sexual dysfunction, and emotional disturbances. The consequences of 416
oestrogen deprivation can be minimized with hormonal replacement, but a large trial has shown that treatment for up to 5.2 years was not beneficial overall and was associated with early risk for coronary heart disease, continuing risk for stroke and venous thromboembolism, and increasing risk for breast cancer with increasing duration. 5 In this retrospective study, we investigated ovarian function and pathology in patients who had undergone total abdominal hysterectomy with preservation of the ovaries, compared with a control group. Patients and methods PATIENTS Data from patients who had undergone total abdominal hysterectomy without oophorectomy at the age of 40 years were evaluated retrospectively. After undergoing total abdominal hysterectomy, these patients had been followed up regularly for at least 8 years in the outpatient clinic: pelvic structures were evaluated with endovaginal sonography and ovarian function was determined from serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol (E2). Data from a control group consisting of randomly chosen post-menopausal patients who required regular follow-up visits were used for comparison. Any record of ovarian pathology was noted in the control patients; they did not have any other significant gynaecological abnormalities. Exclusion criteria for both patients and controls consisted of previous pelvic operation, infertility treatment, elevated tumour markers, the presence of pelvic pathology, polycystic ovarian syndrome, smoking, a family history of early menopause, ovarian cancer and breast cancer. In addition, in the total abdominal hysterectomy group, patients showing a gonadotropin level within the post-menopausal range at the time of operation were excluded from the study. The study was approved by the Ethics Committee of GATA Training Hospital, Ankara, Turkey. ASSESSMENT OF OVARIAN FUNCTION The onset of menopause was determined from changes in the levels of FSH, LH and E2 in serum samples measured with an autoanalyser (Aysym, Abbott Laboratories, Illinois, USA) using a microparticle enzyme immunoassay. Serum FSH and LH levels 20 miu/ml were considered to be a sign of impaired ovarian function. DATA ANALYSIS Results were reported as the mean ± SD. Differences between the total abdominal hysterectomy group and the control group were tested for significance using the independent samples t-test and Fisher s exact test. Statistical analysis was performed using SPSS for Windows 12.0 (SPSS Inc., Chicago, Illinois, USA). A P-value < 0.05 was considered to be statistically significant. Results Data from 29 patients who had undergone total abdominal hysterectomy without oophorectomy and 42 controls randomly chosen from 283 possible subjects were evaluated. In the total abdominal hysterectomy group, the mean age at hysterectomy was 39.1 ± 0.7 years. All women were operated on for benign conditions: 18 for uterine leiomyoma, eight for dysfunctional uterine bleeding, two for endometrial hyperplasia and one for chronic pelvic pain. The age at menopause in the two groups is 417
54 53 Menopausal age (years) 52 51 50 49 48 47 46 n = 26 TAH n = 42 Control FIGURE 1: Age at menopause in patients undergoing total abdominal hysterectomy (TAH) with preservation of the ovaries and in controls, showing the range, upper and lower quartiles and median values (P > 0.05, independent samples t-test) shown in Fig. 1. The mean age of menopause in the total abdominal hysterectomy group was 49.7 ± 1.5 years; this was not significantly different to the mean menopausal age in the control group (50.1 ± 1.3 years). Adnexial pathologies detected during follow-up visits in the two groups are given in Table 1. Significantly more ovarian cysts developed in the total abdominal hysterectomy group than in controls (P < 0.005). Re-laparotomy and bilateral oophorectomy were performed in three of the nine patients in the total abdominal hysterectomy group who developed ovarian cysts. Histopathological findings were compatible with mucinous cystadenoma in one patient and serous cystadenoma in the remaining two patients. TABLE 1: Adnexial pathologies following total abdominal hysterectomy (TAH) with preservation of the ovaries compared with controls TAH (n = 29) Controls (n = 42) No. % No. % P-value a Cyst 9 31.0 2 4.8 < 0.005 Hydrosalpinx 2 6.9 0 0.0 NS a Fisher s exact test. NS, not statistically significant (P > 0.05). 418
Discussion Women undergoing hysterectomy for benign pelvic lesions encounter the dilemma of whether to preserve macroscopically normallooking ovaries. The effect of hysterectomy on the function of preserved ovaries was studied by Siddle et al. 6 They found that the mean age of ovarian failure in the hysterectomized group (45.4 ± 4.0 years) was significantly lower than that in the non-hysterectomized control group (49.5 ± 4.04 years). They attributed this finding to a potential decrease in blood flow to the ovaries due to operational trauma. In contrast, our present study, showed that the age of menopause was comparable in the total abdominal hysterectomy and control groups (49.7 ± 1.5 and 50.1 ± 1.3 years, respectively). Bukovsky et al. 7 examined ovarian function following abdominal hysterectomy with or without unilateral oophorectomy; they reported that 35% of those undergoing unilateral oophorectomy, but only one of the patients with both ovaries preserved, demonstrated impaired ovarian function 6 months after the operation. Thus, if the ovaries are to be preserved at hysterectomy, it would seem to be beneficial to preserve both ovaries. Reports from the Woman s Health Initiative (WHI) study group regarding hormone therapy have raised questions about the efficacy and safety of two particular regimens of postmenopausal hormone treatment, 5,8 resulting in an epidemic of fear and distrust amongst women and physicians. Over-inflated negative data emerging from the oestrogen plus progestin treatment arm of the WHI study have frightened women and given rise to difficult emotions. At present, most physicians agree that the benefits of hormone replacement therapy include a decrease in the incidence of osteoporotic fractures and colorectal cancer, whereas the risks include an increase in breast cancer, coronary heart disease, stroke, thromboembolic events, cognitive impairment, dementia and cholecystitis. Despite these risks, hormone replacement therapy should still be considered the best treatment option for the short-term therapy of menopausal symptoms. When used long-term, however, it should be remembered that, in addition to the medical implications, it is associated with considerable financial cost. Several reports have suggested that the post-menopausal ovary is an important site of androgen synthesis. 9,10 In the present study, there was no difference between the total abdominal hysterectomy and control groups with regard to menopausal age. Preservation of both ovaries in patients aged 40 years may, therefore, not only reduce the need for exogenous oestrogen, but may also maintain a site of post-menopausal androgen synthesis. Zalel et al. 11 reported a high incidence (37/73 patients; 50.7%) of various pelvic lesions following hysterectomy with preservation of at least one ovary compared with hysterectomy without ovarian preservation (5/91 patients; 5.5%). Four of the 37 women who developed pelvic lesions following hysterectomy with preservation of at least one ovary underwent re-operation, whereas none of the five women who developed pelvic lesions following hysterectomy without ovarian preservation required further surgery. In the present study, the incidences of cyst and hydrosalpinx in the total abdominal hysterectomy group were 31.0% and 6.9%, respectively. Although these incidences were significantly higher than those in the control group, they are lower than those reported by Zalel et al. 11 Namnoum et al. 12 determined the risk of re-operation and/or recurrence of symptoms after hysterectomy for the treatment of endometriosis. Among 138 women, the ovaries were preserved in 39 and all ovarian tissue was 419
removed in 109. Of those whose ovaries were preserved, 62% had recurrent pain and 31% required intervention. The authors concluded that the women with ovarian preservation had six times the risk of developing recurrent pain and an eight-fold greater risk of re-operation. None of the cases in the present study underwent total abdominal hysterectomy for endometriosis. The most important benefit of removing the ovaries together with the uterus is that the risk of ovarian carcinoma is reduced to zero. It has been estimated that prophylactic oophorectomy could save between 7% and 15% of patients from developing ovarian carcinoma. 3,13 Hysterectomy on its own, however, seems to be associated with a reduction in the risk of ovarian cancer. A study of ovarian cancer and steroid hormones in women aged 20 54 years found a reduction in the relative risk of ovarian cancer 10 years after hysterectomy, but this reduction was no longer present after two decades. 14 Another study from the USA showed a progressive reduction in the protection conferred by hysterectomy against borderline ovarian tumours with increasing interval from surgery 15 and, in a study by Whittemore et al. 16 the reduction in ovarian cancer risk was still evident but no longer significant 10 years after surgery. In conclusion, this study showed that patients who underwent total abdominal hysterectomy without oophorectomy did not experience premature menopause. We believe, therefore, that a conservative approach involving preservation of the ovaries is preferable in patients 40 years of age who require hysterectomy. Received for publication 4 December 2006 Accepted subject to revision 12 January 2007 Revised accepted 27 March 2007 Copyright 2007 Field House Publishing LLP References 1 Dicker RC, Scally MJ, Greenspan LR, et al: Hysterectomy among women of reproductive age. Trends in the United States, 1970 1978. JAMA 1982; 248: 323 327. 2 Parazzini F, Negri E, La Vecchia C, et al: Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol 1993; 81: 363 366. 3 Gibbs EK: Suggested prophylaxis for ovarian cancer. A 20 year report from cases at Butterworth Hospital. Am J Obstet Gynecol 1971; 111: 756 765. 4 Sightler SE, Boike GM, Estape RE, et al: Ovarian cancer in women with prior hysterectomy: a 14- year experience at the University of Miami. Obstet Gynecol 1991; 78: 681 684. 5 Rossouw JE, Anderson GL, Prentice RL, et al, for the Women s Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women s Health Initiative randomized controlled trial. JAMA 2002; 288: 321 333. 6 Siddle N, Sarrel P, Whitehead M: The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review. Fertil Steril 1987; 47: 94 100. 7 Bukovsky I, Halperin R, Schneider D, et al: Ovarian function following abdominal hysterectomy with and without unilateral oophorectomy. Eur J Obstet Gynecol Reprod Biol 1995; 58: 29 32. 8 Anderson GL, Limacher M, Assaf AR, et al, for the Women s Health Initiative Steering Committee: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women s Health Initiative randomized controlled trial. JAMA 2004; 291: 1701 1712. 9 Adashi EY: The climacteric ovary as a functional gonadotropin-driven androgenproducing gland. Fertil Steril 1994; 62: 20 27. 10 Ushiroyama T, Sugimoto O: Endocrine function of the peri- and postmenopausal ovary. Horm Res 1995; 44: 64 68. 11 Zalel Y, Lurie S, Beyth Y, et al: Is it necessary to perform a prophylactic oophorectomy during hysterectomy? Eur J Obstet Gynecol Reprod Biol 1997; 73: 67 70. 12 Namnoum AB, Hickman TN, Goodman SB, et al: Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril 1995; 64: 898 902. 13 Jacobs I, Oram D: Prophylactic oophorectomy. 420
Br J Hosp Med 1987; 38: 440 449. 14 Cramer DW, Hutchison GB, Welch WR, et al: Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 1983; 71: 711 716. 15 Harlow BL, Weiss NS, Roth GJ, et al: Casecontrol study of borderline ovarian tumors: reproductive history and exposure to exogenous female hormones. Cancer Res 1988; 48: 5849 5852. 16 Whittemore AS, Wu ML, Paffenbarger RS Jr, et al: Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee. Am J Epidemiol 1988; 128: 1228 1240. Address for correspondence Associate Professor V Atay Gülhane Askeri Tip Akademisi Haydarpaşa Eğitim Hastanesi, Kadin Hastaliklari ve Doğum Servisi, TR-34668 Usküdar, Istanbul, Turkey. E-mail: vedatatay@hotmail.com 421