The natural history of adnexal cysts incidentally detected at. transvaginal ultrasound examination in postmenopausal women

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1 Ultrasound Obstet Gynecol 2002; 20: The natural history of adnexal cysts incidentally detected at Blackwell Science, Ltd transvaginal ultrasound examination in postmenopausal women L. VALENTIN* and D. AKRAWI* *Department of Obstetrics and Gynecology, Malmö University Hospital, Malmö, Sweden KEYWORDS: Adnexal diseases, Cyst, Menopause, Ovary, Sonography ABSTRACT Objective To determine the natural history of adnexal cysts incidentally detected at transvaginal ultrasound examination and judged to be benign in postmenopausal women. Methods One hundred and thirty-four postmenopausal women referred for ultrasound examination and found to have an adnexal cyst judged to be benign and not causing any symptoms were followed with transvaginal ultrasound at 3, 6 and 12 months, and then every 12 months. The referring physician treated the patient at his/her own discretion. Results One hundred and sixty cysts were found, 121 (76%) being unilocular and 39 more complicated. Seventy-two cysts (45%) had a largest diameter of 3 19 mm and 88 (55%) had a largest diameter of mm. Median follow-up time was 3 (range, 0.3 8) years. In twelve women (9%) the cysts were removed during follow-up, all their cysts (n = 14) being benign. The indication to operate was a change in cyst morphology or increased cyst size in five (4%) women. In 39 (29%) women, the cysts disappeared; in 18 (13%), new cysts developed; and, in 65 (49%), the number of cysts and their location remained unchanged. Regression of cysts was observed in 54% (33/61) of women < 60 years vs. in 8% (6/73) of those 60 years (P = ). Ultrasound findings remained unchanged in 34% (21/61) of women < 60 years vs. in 77% (56/73) of those 60 years (P = ). Conclusions The results support conservative management of adnexal cysts incidentally detected at transvaginal ultrasound examination and judged to be benign in postmenopausal women. Whether such cysts need to be followed-up at all and, if they do, how often and for how long, remains an open question. INTRODUCTION With the introduction of transvaginal ultrasound into clinical gynecological practice, it has become evident that adnexal cysts, especially simple cysts (i.e. unilocular, anechoic cysts with smooth walls), are quite common in postmenopausal women. They have been found in as many as 15 17% of asymptomatic postmenopausal women 1 3. There is still uncertainty as to how incidentally detected adnexal cysts with benign ultrasound morphology in postmenopausal women should be treated. We report the natural history of adnexal cysts incidentally detected at transvaginal ultrasound examination and judged to be benign in 134 postmenopausal women. METHODS Consecutive postmenopausal women, referred for ultrasound examination by the first author between 25 June 1991 and 14 December 1998, and found to have one or more adnexal cysts judged to be benign and not causing any symptoms, were offered expectant management by ultrasound follow-up by the first author. Those who accepted and were followed for at least 1 year, and those who accepted but were operated on or whose cysts disappeared during the first year of follow-up, were included. Follow-up stopped on the 24 November A woman was considered to be postmenopausal if she reported at least 1 year of amenorrhea after the age of 40 years, provided that the amenorrhea could not be explained by disease or medication. Of 162 women offered ultrasound follow-up of an adnexal cyst by the first author during the inclusion period, 134 accepted and fulfilled the inclusion criteria. Characteristics of the 134 women included and the 28 women excluded are shown in Table 1. Symptoms at presentation did not differ significantly between the women who were included and Correspondence: Dr L. Valentin, Department of Obstetrics and Gynecology, Malmö University Hospital, S Malmö, Sweden ( lil.valentin@obst.mas.lu.se) Accepted ORIGINAL PAPER

2 excluded. The women excluded were older than those included (even though the difference was not statistically significant), and a greater proportion of them died during the follow-up period, but the causes of death were similar in the two groups. The cysts in the women included and excluded were similar in size and type. The most common reason for the women excluded to decline or break follow-up was that they considered themselves too old or unhealthy, or that they preferred to be followed-up by their private gynecologist. The women included underwent transvaginal ultrasound examination by the first author at 3, 6 and 12 months, and then every 12 months. If the cyst increased in size or changed its morphology, additional ultrasound examinations were performed. All results were forwarded to the referring physician, who treated the patient at his/her own discretion. The women were examined in the lithotomy position with an empty bladder. The ultrasound system used was an Acuson 128 XP with a 5-MHz or a 7.5-MHz transvaginal transducer (Acuson Inc., Mountain View, CA, USA), or a Sequoia 512 ultrasound system (Acuson Inc.) with a 5 8- MHz transvaginal transducer. The uterus and the adnexa were identified. The length (L), depth (D) and width (W) of any adnexal lesion were measured in cm with calipers on the frozen ultrasound image, lesion volume (cm 3 ) being calculated as L D W 0.5. The largest diameter of each lesion and the mean of its three diameters were also used to describe the size of the lesion. Based on the gray-scale ultrasound image, each lesion was classified as a unilocular cyst (a unilocular cyst without septa and without solid parts or papillary projections), a multilocular cyst (a cyst with a septum or septa but no solid parts or papillary projections), a unilocular solid cyst (a unilocular cyst containing solid parts or papillary projections but no septa), a multilocular solid tumor (a tumor with a septum or septa and solid parts or papillary projections) or a solid tumor (a tumor where the solid components comprised 80% or more of the tumor) 4,5. A solid tumor was considered to be the most complex type of tumor, followed in descending order by multilocular solid cysts, unilocular solid cysts, multilocular cysts and unilocular cysts. Ultrasound morphology was considered to improve if a complex cyst changed to a less complex one, and to deteriorate if a less complex cyst became more complex. A cyst was considered benign or malignant on the basis of subjective evaluation of the gray-scale ultrasound image as previously described 6,7. Increase in cyst size was defined as a positive difference between the largest diameter of the cyst at the last examination and that at the first examination, or as a positive difference between the mean diameter of the cyst at the last examination and that at the first examination. Table 1 Characteristics of women included and excluded Characteristic Included (n = 134) Excluded (n = 28) P Age at inclusion (years, median (range)) 61 (47 87) 70 (49 89) 0.22* Years past menopause (median (range)) 11 (1 39) 16 (2 41) 0.18* Symptoms at presentation (n (%)) None 50 (37) 7 (25) 0.21 Postmenopausal bleeding 51 (38) 14 (50) 0.31 Abdominal pain 22 (16) 3 (11) Other 11 (9) 4 (14) Bilateral cysts (n (%)) 26 (19) 8 (29) 0.41 Type of right-sided cyst (n (%)) Unilocular 69 (78) 12 (60) 0.15 Multilocular 10 (11) 5 (25) Unilocular solid 2 (2) 0 Multilocular solid 7 (8) 2 (10) Not described 0 1 (5) Size of right-sided cyst (median (range)) Largest diameter (mm) 23 (3 80) 20 (4 74) 0.85* Mean diameter (mm) 18 (3 63) 18 (4 62) 0.78* Volume (cm 3 ) 3.2 ( ) 2.6 ( ) 0.59* Type of left-sided cyst (n (%)) Unilocular 52 (72) 10 (63) 0.55 Multilocular 7 (10) 4 (25) Unilocular solid 3 (4) 1 (6) Multilocular solid 10 (14) 0 Not described 0 1 (6) Size of left-sided cyst (median (range)) Largest diameter (mm) 21 (4 75) 21 (4 60) 0.58* Mean diameter (mm) 17 (4 70) 17 (3 50) 0.61* Volume (cm 3 ) 2.7 ( ) 2.5 (0.2 54) 0.58* Died during follow-up (n (%)) 11 (8) 8 (29) Cause of death (n (%)) Cardiovascular disease 8 (73) 6 (75) Extragenital cancer 3 (27) 2 (25) Cyst characteristics at inclusion are shown. *Mann Whitney test. Chi-squared test. Fisher s exact test. Ultrasound in Obstetrics and Gynecology 175

3 Information on operations, histological diagnoses, and autopsy results was retrieved retrospectively from hospital records, and information on causes of death from the mortality registries of Swedish Statistics ( and the National Board of Health and Welfare ( Statistical calculations were carried out using the Statview 4.5 statistical program (Abacus Concepts, Inc., Berkeley, CA, USA). The Mann Whitney test was used to examine the statistical significance of differences in unpaired continuous data that manifested a skewed distribution, and Student s t-test was used to examine the statistical significance of differences in normally distributed unpaired continuous data. Chi-squared test or Fisher s exact test were used as appropriate to test the statistical significance of differences in categorical data. P < 0.05 (two-tailed) was considered statistically significant. RESULTS Age of patients, the number of years past menopause and the size and type of cysts at inclusion are shown in Table 1. Bilateral cysts were found at the first examination in 26 (19%) women. Most cysts were small, 32 (20%) having a largest diameter of less than 10 mm, 40 (25%) a largest diameter of mm, 39 (24%) a largest diameter of mm, 15 (9%) a largest diameter of mm, 19 (12%) a largest diameter of mm and 15 (9%) a largest diameter of 50 mm or more. The number of women with cysts of different sizes is shown in Figure 1. Forty-eight (35%) of the women had at least one cyst with a largest diameter of 30 mm. Of the 160 cysts, 121 (76%) were unilocular. Median follow-up time was 3 (range, 0.3 8) years (follow-up < 1 year is explained by operation or disappearance of the cyst within the first year of follow-up), and median number of follow-up examinations was 5 (range, 2 12). Figure 1 Number of women with cysts of different size (largest diameter of largest cyst). Twelve (9%) women were operated on, the histological diagnoses of the removed adnexa being: simple cyst (n = 3), serous cystadenoma (n = 5), para-ovarian cyst (n = 2), endometrioma (n = 1) and dermoid cyst (n = 1). The reasons for operating instead of continuing ultrasound follow-up were: increase in cyst size (n = 2; the increase of the largest cyst diameter after 2 and 4.5 years of observation being at least 20 mm), change in ultrasound morphology (n = 3; in the first case, a papillary projection was detected in a unilocular cyst 2.5 years after inclusion; in the second case, irregularities in the wall of a unilocular cyst were detected 1 year after inclusion; and, in the third case, a lesion that had been characterized as a unilocular cyst with echogenic contents was interpreted as more likely to be a solid lesion 3 years after inclusion, the true diagnosis being endometrioma), patient s anxiety (n = 2), doctor s anxiety (n = 1), pain (n = 2; one unilocular cyst removed 6 years after inclusion and one multilocular cyst removed 9 months after inclusion), rectal prolapse (n = 1) and complex atypical adenomatous hyperplasia of the endometrium (n = 1). The cyst in the woman operated because of rectal prolapse was a simple ovarian cyst. In addition, this woman was found to have pseudomyxoma peritonei originating from the appendix. Ultrasound examination had not revealed any signs of this, despite the last examination having been performed 2 months before the operation. In 39 (29%) women, the cysts regressed completely or partially (partial regression being defined as regression of one of two cysts in case of bilateral cysts); in three (2%) women, a unilateral cyst disappeared but another one was detected on the contralateral side; in 15 (11%) women, an additional cyst was detected on the contralateral side of a remaining unilateral cyst; and in 65 (49%) women, the number of cysts and their location remained unchanged. The 57 women with changing ultrasound findings (regression of cysts, findings of new cysts) and the 12 women who had cysts removed were younger and had passed the menopause more recently than the 65 women with unchanged ultrasound findings (median age of the women with changing ultrasound findings, 56 years; range, 47 85; median age of those operated on, 58 years; range, vs. median age of those with unchanged ultrasound findings, 70 years; range, 48 87; P < and P = 0.07, respectively; median number of years past menopause, 6 years; range, 1 31; and 8 years; range, 2 30 vs. 19 years; range, 2 39; P < and P = 0.02, respectively). Partial or complete regression of cysts was observed in 54% (33/61) of women < 60 years vs. in 8% (6/73) of those 60 years (P = ). Ultrasound findings remained unchanged (with regard to number and location of cysts) in 34% (21/61) of women < 60 years vs. in 77% (56/73) of those 60 years (P = ). Eleven (8%) women died during the follow-up period, the causes of death being either cardiovascular disease or extragenital malignancy (Table 1). In 14 of the deceased women, the cyst(s) remained unchanged during the observation period; in two women, new cysts were detected. The cysts were not related to the cause of death in any case. One woman underwent autopsy. Her cyst was a benign paraovarian cyst. 176 Ultrasound in Obstetrics and Gynecology

4 Table 2 Characteristics of right-sided cysts that persisted, were removed at operation, or disappeared during follow-up Characteristic Persisted (n = 57) Persisted and removed (n = 6) Disappeared (n = 25) P Age at inclusion (years, median (range)) 70 (47 86) 62 (54 85) 53 (47 76) < * Years past menopause at inclusion (median (range)) 19 (2 39) 11 (2 30) 3 (1 26) < * Bilateral at inclusion (n (%)) 16 (28) 4 (67) 6 (24) 0.61 Type of cyst at inclusion (n (%)) Unilocular 40 (70) 5 (83) 24 (96) 0.01 Multilocular 9 (16) 0 1 (4) Unilocular solid 2 (4) 0 0 Multilocular solid 6 (10) 1 (17) 0 Largest diameter at inclusion (mm, median (range)) 24 (4 80) 25 (17 41) 13 (3 46) 0.001* Mean diameter at inclusion (mm, median (range)) 20 (3 63) 23 (15 34) 11 (3 42) * Change in size between first and last examination (mm, mean ± SD (range)) Largest diameter +1.1 ± ( 38 30) +7.7 ± 9.58 ( 20 22) Mean diameter +0.2 ± ( 32 31) +6.2 ± 7.88 ( 3 18) Change in type between first and last examination (n (%)) Unchanged 44 (77) 5 (83) Improvement 4 (7) 0 Deterioration 9 (17) 1 (17) SD, standard deviation. P-values refer to comparison between all cysts that persisted (including those removed) and those that disappeared. None of the differences between cysts that persisted and were not removed and those that persisted and were removed were statistically significant. *Mann Whitney test. Fisher s exact test. Table 3 Characteristics of left-sided cysts that persisted, were removed at operation, or disappeared during follow-up Characteristic Persisted (n = 39) Persisted and removed (n = 8) Disappeared (n = 25) P Age at inclusion (years, median (range)) 69 (49 87) 63 (51 85) 55 (47 73) * Years past menopause at inclusion (median (range)) 17 (1 34) 8 (2 30) 4 (1 23) * Bilateral at inclusion (n (%)) 12 (31) 3 (37) 11 (44) 0.45 Type of cyst at inclusion (n (%)) Unilocular 26 (67) 6 (75) 20 (80) 0.42 Multilocular 6 (15) 1 (13) 0 Unilocular solid 1 (3) 0 2 (8) Multilocular solid 6 (15) 1 (12) 3 (12) Largest diameter at inclusion (mm, median (range)) 21 (4 71) 30 (16 40) 13 (4 75) 0.04* Mean diameter at inclusion (mm, median (range)) 19 (4 52) 26 (14 37) 12 (4 70) 0.009* Change in size between first and last examination (mm, mean ± SD (range)) Largest diameter 1.6 ± ( 42 25) +6 ± ( 5 28) Mean diameter 1.7 ± 9.54 ( 27 19) +4 ± ( 5 22) Change in type between first and last examination (n (%)) Unchanged 28 (72) 4 (50) Improvement 6 (15) 1 (13) Deterioration 5 (13) 3 (37) SD, standard deviation. P-values refer to comparison between all cysts that persisted (including those removed) and those that disappeared. None of the differences between cysts that persisted and were not removed and those that persisted and were removed were statistically significant. *Mann Whitney test. Chi-squared test. Results with regard to cysts are shown in Tables 2 4. Cysts that disappeared were found in younger women, and they were smaller and tended to be unilocular more often than cysts that persisted. For persistent cysts (including those removed at operation), there was no systematic change in size. The changes were normally distributed. The mean change in the largest diameter was +1.7 ± mm (standard deviation) for right-sided cysts and 2.7 ± mm for left-sided cysts. The corresponding figures for changes in mean diameter were +0.8 ± mm and 0.6 ± 9.91 mm. Morphology also remained unchanged in most persistent cysts (78% of right-sided, 68% of left-sided). There were some differences between the natural history of unilocular cysts and that of more complicated cysts. Right-sided unilocular cysts disappeared more often than right-sided complicated cysts (24/69 vs. 1/19; 38% vs. 5%; P = 0.03). For left-sided cysts, the regression rate of unilocular cysts was slightly higher but not significantly different from that of more complicated cysts (20/52 vs. 5/20; 38% vs. 25%; P = 0.42). Right-sided complicated cysts tended to increase in size more often than Ultrasound in Obstetrics and Gynecology 177

5 Table 4 Cysts that developed during follow-up Characteristic Right-sided (n = 12) Left-sided (n = 7) P* Age at inclusion (years, median (range)) 59 (49 85) 68 (52 84) 0.40 Years past menopause at inclusion (median (range)) 9 (1 23) 18 (8 31) 0.13 Type of cyst at last examination (n (%)) Unilocular 10 (83) 7 (100) Multilocular 1 (8) Unilocular solid 0 Multilocular solid 1 (8) Size at last examination (mm, median (range)) Largest diameter 26 (4 70) 8 (3 25) 0.10 Mean diameter 18 (3 58) 7 (3 21) 0.19 *Mann Whitney test. right-sided unilocular cysts, the mean change in the largest diameter being +8 ± 16.1 mm vs. 1 ± 10.8 mm (P = 0.01), and the mean change in the mean diameter +5 ± 13.5 mm vs. 1 ± 9.0 mm (P = 0.04). For left-sided cysts, the change in size was similar for complicated cysts and unilocular cysts, (mean change in the largest diameter 1.5 ± 16.9 mm vs ± 12.2 mm; P = 0.69; mean change in the mean diameter 1.7 ± 11.9 mm vs. 0.1 ± 9.0 mm; P = 0.61). DISCUSSION The few women operated on were found to have benign cysts. The clinical course in the remaining women strongly suggests that none of the cysts that were left in situ were malignant at inclusion or became malignant during follow-up. This is in agreement with the results of other studies where postmenopausal women with incidentally detected adnexal cysts judged to be benign at ultrasound examination were followed-up by ultrasound 1,8 12. However, all the studies cited, except one 9, included only simple cysts. The studies cited together with ours comprised a total number of 333 women. The small number of women studied limits the generalizability of the results. Bailey et al. 13 and Conway et al. 14 followed 256 and 116 simple cysts with ultrasound in asymptomatic women stated to be postmenopausal or 50 years, and found none of these cysts to be or to become malignant during follow-up. However, some of the women in these two studies might not have been postmenopausal, women 50 years without regard to menopausal status being included in the first study 13 and postmenopausal status not being defined in the second study 14. It came as a surprise to us that so many cysts disappeared and that so many new cysts developed during the follow-up period, cysts being found to disappear in 29% of the women and new cysts to develop in 13% of the women. These results are very similar to those of Levine et al. 1. They found that small (3 50 mm) simple adnexal cysts disappeared in 26% (13/49) of asymptomatic postmenopausal women, and that new cysts developed in 17% (31/184) during a follow-up period of approximately 2 years. However, unlike Levine et al. 1, who reported that regression of cysts or development of new cysts were not related to the number of years past menopause, we found that women in whom cysts disappeared or developed were younger and had passed the menopause more recently than those in whom ultrasound findings remained unchanged. The reason for the discrepancy is unclear. Bailey et al. 13 reported that 49% (125/256) of unilocular cysts detected at ultrasound screening of postmenopausal women or women 50 years disappeared within 60 days and, in agreement with our results, they found the regression rate to be much higher in women aged years than in women 60 years. Conway and colleagues also found a high regression rate (23%; 27/116) of incidentally detected simple cysts in postmenopausal women 14. However, a substantial number of women in the studies of Bailey et al. 13 and Conway et al. 14 may not have been postmenopausal. It might be argued that the disappearance of cysts and the development of new cysts reflected the inability of the ultrasound examiner to correctly identify cysts and not a true change. We find this unlikely because, had this been the case, the disappearance of cysts and the development of new cysts would be expected to have occurred at random and to be unrelated to the age of the women. We find it more reasonable to believe that the changing ultrasound findings in the younger women are explained by a considerable proportion of the cysts in these women being follicular cysts that developed or disappeared during the observation period 15. The cysts in the older women with more stable ultrasound findings are more likely to have been inclusion cysts or neoplastic cysts. These are expected not to disappear, but some may develop over time. In other studies of asymptomatic cysts in postmenopausal women, the cysts disappeared in a varying proportion of women (0 87%), but development of new cysts during follow-up was not described The reason for the variability in results is unclear, even though there may be differences between the studies with regard to patient selection, experience of the ultrasound examiners and the quality of the ultrasound equipment used. Most of the cysts included in the studies cited 8 12 were simple cysts with a diameter < 50 mm (minimum size was not always given) that were followed-up for at least 1 year in women who appear to have been of fairly similar age (the age and the number of years past menopause were not clearly described in all studies). Although some changes in size did occur in cysts that persisted, these changes were normally distributed and equally often positive and negative. Clinically, these changes were usually interpreted as measurement errors and not as true changes in cyst size. Only two of the women who 178 Ultrasound in Obstetrics and Gynecology

6 underwent surgery were operated on because of an increase in cyst size. We have been unable to find any publications on the reproducibility of ultrasound measurements of adnexal cysts but, given the compressibility and mobility of many cysts, measurement errors may be substantial. Some who followed asymptomatic cysts in postmenopausal women with ultrasound reported a small proportion (4 11%) of the cysts to increase in size during the observation period 1,8,12, whereas others observed no cases of increased cyst size 10,11. Decrease in cysts size occurred in 3 29% of simple cysts followed by ultrasound 1,8,10. In some of the studies cited the measurement technique was not described clearly 1,10,11 and in only one was there a clear definition of change 1. Our judgement is that true size remained unchanged in most persistent cysts in our study. Cyst morphology changed in 29 (26%) of the 110 persisting cysts, improvement being observed in 11 cysts and deterioration in 18. Some of these changes might be explained by technical factors. Thin septae or small solid areas that may have been overlooked at the beginning of the study might have become visible at the end of the study, when ultrasound equipment with better image quality was used. Not only deterioration, but also improvement in cyst morphology might be explained by technical factors; for example, shadows from gas in the intestines preventing the visualization of thin septa or small solid areas on some, but not all, occasions. Only three of the women who underwent surgery were operated on because of a change in cyst morphology. In the remaining cases of changing cyst morphology, the change was considered to be clinically irrelevant and probably to be explained by technical factors. Thus, our judgement is that true morphology remained unchanged in most persisting cysts. In our study, we included not only simple cysts, but also more complicated cysts with a clearly benign appearance. We felt confident in doing so, because our ability to correctly discriminate between benign and malignant adnexal lesions is good 6,7. Moreover, in a recently published study, it was shown that benign complex cystic adnexal lesions do not share the established risk factors for ovarian malignancy 16. Most other studies on the natural history of asymptomatic cysts in postmenopausal women 8,10 12 included only simple cysts. Only one other study possibly included a few complicated cysts 9. In our study, the natural history of the more complicated cysts was similar to that of the unilocular cysts (corresponding to the simple cysts in the other studies 8 12 ). All cysts followed a benign course, most of them either disappeared or remained unchanged in size or morphology (even though right-sided complicated cysts increased in size more often and disappeared less often than right-sided unilocular cysts) and only two cysts appear to have caused symptoms during the follow-up period (even though the relationship between the pain and the cyst was uncertain in both women who were operated on because of pain). In only five (4%) of the 134 women was a change in size or morphology of the cysts judged to be clinically important and considered to justify surgery. This is in agreement with the results reported by Conway et al. 14. In their series of 116 cysts followed by ultrasound, only six (5%) were operated on because of a change in cyst size or cyst morphology. It is a clinical dilemma that neither the natural history of apparently benign and incidentally detected adnexal lesions nor that of ovarian cancer is completely known. A strong relationship between ovarian cancer and asymptomatic cystic adnexal lesions incidentally detected at ultrasound examination in postmenopausal women seems unlikely for the following reasons. First, there is a high prevalence of cystic adnexal lesions in asymptomatic postmenopausal women (up to 15 17% 1 3 ) but a very low incidence of ovarian cancer in women 50 years ( % 17 ). Second, in a study where women screened for ovarian cancer with ultrasound were followed-up for a mean of 15.5 years, ovarian cancer mortality was not lower than expected, despite most of the benign adnexal lesions detected at screening having been surgically removed within the frame of the screening program (approximately 60% of the women screened and operated on were postmenopausal) 18. This suggests that most ovarian cancers develop in ovaries judged to be normal at ultrasound examination and not from adnexal cysts. Third, complex cystic adnexal lesions do not share the established risk factors for ovarian malignancy 16. To determine with certainty whether benign-looking adnexal lesions incidentally detected at ultrasound examination in postmenopausal women are associated with an increased risk of ovarian cancer (either as direct precursors or as a predisposing factor), and to determine with confidence the size of a possibly increased risk, hundreds of thousands of women would have to be screened with transvaginal ultrasound, with any benign looking adnexal lesions being left in situ. These women would then need to be followed-up for many years with regard to the development of ovarian cancer. Awaiting the results of such a study, we must base our clinical management of incidentally detected adnexal cysts with benign ultrasound morphology in postmenopausal women on indirect and weaker evidence. The results of our study support conservative management, because all 160 cysts followed a benign course, 95% of those that did not disappear remained essentially unchanged in size and morphology and only two (1%) might have caused symptoms during follow-up. Whether benign-looking cysts incidentally detected at ultrasound examination in postmenopausal women need to be followed-up at all, and if they do, how often and for how long, remains an open question. ACKNOWLEDGMENTS The study was supported by grants from the Malmö General Hospital Cancer Foundation, Funds administered by the Malmö Health Care Administration, a governmental grant for clinical research ( ALF-medel and Landstings finansierad regional forskning ) and the Swedish Medical Research Council (grant nos. B6 17X A, K98-17X A and K X A). REFERENCES 1 Levine D, Gosink BB, Wolf SI, Feldesman MR, Pretorius DH. Simple adnexal cyst: the natural history in postmenopausal women. 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