Ovarian Volume Related to Age

Gynecologic Oncology 77, 410 – 412 (2000) doi:10.1006/gyno.2000.5783, available online at http://www.idealibrary.com on

Ovarian Volume Related to Age E. J. Pavlik, Ph.D., P. D. DePriest, M.D., H. H. Gallion, M.D., F. R. Ueland, M.D., M. B. Reedy, M.D., R. J. Kryscio, Ph.D., and J. R. van Nagell, Jr., M.D. 1,2 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and the Department of Statistics, University of Kentucky Medical Center, Lexington, Kentucky 40536 Received October 13, 1999

portant to know the range of normal ovarian volume related to age and body habitus. The following investigation was performed to determine the relationship of ovarian volume to patient age, height, weight, and menopausal status. The effect of exogenous hormones on an ovarian volume was also evaluated.

Objective. The goal of this study was to determine the relationship of ovarian volume to age, height, and weight in women undergoing transvaginal sonography. Methods. Thirteen thousand nine hundred sixty-three women 25–91 years of age undergoing annual transvaginal sonography as part of the University of Kentucky Ovarian Cancer Screening Program were the subjects for this investigation. Each ovary was measured in three dimensions, and ovarian volume was calculated using the prolate ellipsoid formula (L ⴛ H ⴛ W ⴛ 0.523). Mean ovarian volume according to age was calculated for each decade of life. Results. Data were obtained from 58,673 observations of ovarian volume. Mean ovarian volume was 6.6 ⴞ 0.19 cm 3 in women less than 30 years of age; 6.1 ⴞ 0.06 cm 3 in women 30 –39; 4.8 ⴞ 0.03 cm 3 in women 40 – 49; 2.6 ⴞ 0.01 cm 3 in women 50 –59; 2.1 ⴞ 0.01 cm 3 in women 60 – 69; and 1.8 ⴞ 0.08 cm 3 in women >70. Mean ovarian volume was 4.9 ⴞ 0.03 cm 3 in premenopausal women and 2.2 ⴞ 0.01 cm 3 in postmenopausal women (P < 0.001). The use of exogenous estrogens was associated with a significant reduction in ovarian volume in women 40 –59 years of age, but not in women > 60. Ovarian volume was unrelated to patient weight but was greater in tall women (>68 in.) than in short women (<58 in.). Conclusion. There is a statistically significant decrease in ovarian volume with each decade of life from age 30 to age 70. Mean ovarian volume in premenopausal women is significantly greater than that in postmenopausal women. The upper limit of normal for ovarian volume is 20 cm 3 in premenopausal women and 10 cm 3 in postmenopausal women. © 2000 Academic Press

SUBJECTS AND METHODS

INTRODUCTION

Subjects for this investigation were enrolled in the University of Kentucky Ovarian Cancer Screening Project from 1987 to 1997. All study participants completed a questionnaire concerning age, height, weight, past medical and surgical history, history of hormonal intake, and menopausal status. Women eligible for participation in this trial included (1) asymptomatic women over the age of 25 with a documented family history of ovarian cancer in at least one primary or secondary relative, and (2) all asymptomatic postmenopausal women or women over the age of 50 years. Postmenopausal was defined as the absence of menses for a minimum of 12 months. Informed consent was obtained as required by the University of Kentucky Institutional Review Board. Transvaginal sonography (TVS) was performed by certified technologists using Aloka 620 units with 5.0-MHz vaginal probes. A permanent hard copy of each sonogram was generated, and both left and right ovarian dimensions were measured. Ovarian volume was calculated using the prolate ellipsoid formula (L ⫻ H ⫻ W ⫻ 0.523). Patients with a solid or cystic ovarian tumor detected by sonography were excluded from this investigation since the purpose of this study was to determine normal ovarian volume. The duration and type of hormonal use as well as the menopausal status of each patient were recorded at the time of the first visit. Data were maintained on a networked MEDLOG database as previously reported [2]. Univariate analysis. A series of one-way analysis of variance (ANOVA) procedures were used to compare the mean ovarian volume among the levels of each of the five independent factors: hormonal replacement, menopausal status, age category, height category, and weight category. Multivariate analysis was performed and another one-way ANOVA was

Sonographic screening for ovarian cancer is based on the identification of subtle changes in ovarian volume and morphology associated with early neoplasia [1– 4]. Since a persistent increase in ovarian volume is used as an indicator for more extensive patient evaluation in screening algorithms, it is im1

American Cancer Society Professor of Clinical Oncology. To whom correspondence should be addressed at Division of Gynecologic Oncology, Room MN308, UKMC, 800 Rose Street, Lexington, KY 40536. Fax: (606) 323-1018. 2

0090-8258/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

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OVARIAN VOLUME RELATED TO AGE

TABLE 1 Ovarian Volume Related to Age

TABLE 3 Ovarian volume (cm 3)

Ovarian volume (cm 3)

Na

Age ⬍30 30–39 40–49 50–59 60–69 ⬎70

Statistical significance b

6.6 ⫾ 0.19 c 6.1 ⫾ 0.06 4.8 ⫾ 0.03 2.6 ⫾ 0.01 2.1 ⫾ 0.01 1.8 ⫾ 0.01

444 3,259 9,963 24,321 15,678 2,226

P P P P P

⬍ ⬍ ⬍ ⬍ ⬍

0.001 0.001 0.001 0.001 0.001

Age

Estrogen replacement

No estrogen

Statistical significance

40–49 50–59 60–69 ⱖ70

4.25 ⫾ 0.13 a 2.23 ⫾ 0.02 1.98 ⫾ 0.02 1.85 ⫾ 0.04

4.92 ⫾ 0.04 2.68 ⫾ 0.02 1.97 ⫾ 0.01 1.74 ⫾ 0.02

P ⬍ 0.001 P ⬍ 0.001 N.S. N.S.

a

N ⫽ number of observations. b Based on comparison of mean ovarian volumes from one decade to the preceding decade. c Mean ⫾ SEM.

Mean ⫾ SEM.

a

constructed to compare mean ovarian volume among groups formed by combinations of the factors found to be significant in the univariate analysis and having adequate cell sizes. In all ANOVAs, post hoc comparison of means was based on Fisher’s protected least significant difference procedure, and statistical significance was set at the 0.05 level. RESULTS Data concerning ovarian volume were obtained on 13,963 patients who were screened annually from 1 to 11 years. The relationship of ovarian volume to age is presented in Table 1. Mean ovarian volume in women ⬍30 years was 6.6 ⫾ 0.19 cm 3. There was a progressive reduction in mean ovarian volume with increasing age as follows: 6.1 ⫾ 0.06 cm 3 in women 30 –39; 4.8 ⫾ 0.3 cm 3 in women 40 – 49; 2.6 ⫾ 0.01 cm 3 in women 50 –59; 2.1 ⫾ 0.01 cm 3 in women 60 – 69; and 1.8 ⫾ 0.08 cm 3 in women ⱖ70 (Table 1). There was a statistically significant reduction in ovarian volume with each decade of life from age 30 to age 70. Mean ovarian volume decreased from 4.9 ⫾ 0.03 cm 3 in premenopausal women to 2.2 ⫾ .01 cm 3 in postmenopausal women (P ⬍ 0.001).

The relationship of ovarian volume to height is illustrated in Table 2. Ovarian volume did not increase steadily with height. Rather, there was a statistical break in the data such that women ⱖ68 in. tall had larger mean ovarian volumes (3.4 ⫾ 0.4 cm 3) than women ⬍68 in. tall (2.9 ⫾ 0.01 cm 3) (P ⬍ 0.0001). The relationship between height and ovarian volume was confirmed also by multivariate analysis. There was no apparent relationship between a woman’s ovarian volume and her weight or parity. Forty-four percent of women screened (6702) reported ever taking exogenous estrogen. The most common regimen was Premarin 0.625 mg po, and the mean duration of hormone use was 6.0 years. The relationship of ovarian volume to estrogen use according to age is presented in Table 3. There was a statistically significant (P ⬍ 0.001) reduction in ovarian volume with estrogen use in women 40 –59 years of age. However, no such association was present in women ⱖ60 years of age. DISCUSSION Pelvic examination is notoriously inaccurate in assessing ovarian volume [5]. Consequently, subtle changes in ovarian

TABLE 2 Ovarian Volume Related to Height Height (in.)

Na

Ovarian volume (cm 3)

⬍60 60–63 64–67 68–71 ⬎71

929 19,398 33,646 5,587 131

2.9 ⫾ 0.08 b 2.8 ⫾ 0.02 3.0 ⫾ 0.01 3.4 c ⫾ 0.04 3.4 c ⫾ 0.19

N ⫽ number of observations. Mean ⫾ SEM. c 3.4 cm 3 is significantly greater than 2.8, 2.9, or 3.0 cm 3 (P ⬍ 0.001). However, 2.8 cm 3 is not significantly different from 2.9 or 2.9 cm 3 from 3.0 cm 3. a b

FIG. 1. Ovarian volume related to age. Individual ovarian volumes were calculated at the time of initial and subsequent annual visits. Mean ovarian volumes were calculated according to age. The histogram shows the number of observations at each age. Mean values are represented by solid circles and median values by open circles.

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FIG. 2. Ovarian volume related to age. The 95% upper confidence limit (mean ⫹ 1.96 ⫻ SD) shows the upper range into which individual normal ovarian volume measurements will fall. Mean values are indicated by solid circles. Bars indicate mean ⫹ 1.96 ⫻ SD.

size or morphology associated with early-stage ovarian malignancy are often missed by clinical examination. With the advent of TVS, it is now possible to detect small changes in ovarian volume and structure associated with ovarian neoplasia. The findings of this investigation are important in that they establish a range of normal ovarian volumes for women over the age of 30. It is now apparent that ovarian size begins to decrease after the age of 30. With each decade, there is a statistically significant reduction in ovarian volume until the age of 70. Ovarian size decreases with menopause but this reduction continues well beyond cessation of menses. In a previous investigation of 2221 postmenopausal women, Goswamy and colleagues [6] reported that mean ovarian volume was 3.57 cm 3. The mean age of patients in their study was 56.3 years. In the present investigation, mean ovarian volume in women 50 –59 years of age was 2.6 ⫾ 0.01 cm 3, and mean ovarian volume for all postmenopausal women was 2.2 ⫾ 0.01 cm 3. As expected, ovarian volume was smaller in women 40 –59 years of age taking estrogen compared with those not taking replacement hormones. Exogenous hormones inhibit gonadotropin production and their trophic effect on ovarian tissue, thereby reducing ovarian volume [7]. However, this suppressive effect of estrogen on ovarian volume was not apparent in women over the age of 60. The implication of these findings for ovarian cancer screening is significant. In many screening programs, the presence of ovarian enlargement confirmed on transvaginal sonography initiates a series of events that include repeat sonography, doppler flow assessment of ovarian vasculature, and serum marker determinations [4, 8, 9]. These additional tests are more

time consuming and costly for the patient. Therefore, it is important that the definition of abnormal ovarian volume be based on accurate data concerning normal ovarian volume related to patient age. By convention, abnormal ovarian enlargement has been defined as two standard deviations above normal ovarian volume [7]. Using this definition and data from the present investigation, the upper limit of normal ovarian volume would be 20 cm 3 for premenopausal women and 10 cm 3 for postmenopausal women (Fig. 2). In a recent screening trial, Bailey and co-workers [10] reported that 115 of 7705 (1.5%) asymptomatic women ⬎50 years of age had persisting complex ovarian tumors ⬎10 cm 3 in volume confirmed by transvaginal sonography. Ovarian cancer was noted in 7.8% of these patients. Based on findings of the present investigation, the authors conclude that a persisting ovarian volume ⬎20 cm 3 in premenopausal women or ⬎10 cm 3 in postmenopausal women is abnormal and warrants further evaluation. REFERENCES 1. van Nagell JR, DePriest PD, Puls LE, Donaldson ES, Gallion HH, Pavlik EJ, Powell DE, Kryscio RJ: Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography. Cancer 68:458 – 462, 1991 2. DePriest PD, Gallion HH, Pavlik EJ, Kryscio RJ, van Nagell JR: Transvaginal sonography as a screening method for the detection of early ovarian cancer. Gynecol Oncol 65:408 – 414, 1997 3. Goswamy RK, Campbell S, Whitehead MI: Screening for ovarian cancer. Clin Obstet Gynecol 10:621– 643, 1983 4. DePriest PD, Shenson D, Fried A, Hunter JE, Andrews SJ, Gallion HH, Pavlik EJ, Kryscio RJ, van Nagell JR: A morphology index based on sonographic findings in ovarian cancer. Gynecol Oncol 51:7–11, 1993 5. Roman LD, Muderspach LI, Stein SM, Laifer-Narin S, Groshen S, Morrow CP: Pelvic examination, tumor maker level, and gray-scale and Doppler sonography in the prediction of pelvic cancer. Obstet Gynecol 89:493–500, 1997 6. Goswamy RK, Campbell S, Royston JP, Bhan V, Battersby RH, Han VJ, Whitehead MI, Collins WP: Ovarian size in postmenopausal women. Br J Obstet Gynecol 95:795– 801, 1988 7. Van der Westhizen S, van der Spuy ZM: Ovarian morphology as a predictor of hormonal values in polycystic ovary syndrome. Ultrasound Obstet Gynecol 7:335–341, 1996 8. Bourne TH, Campbell S, Reynolds KM, Whitehead MI, Hampson J, Royston P, Crayford TJ, Collins WP: Screening for familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging. Br Med J 306:1025–1029, 1993 9. Jacobs I, Davies AP, Bridges J: Prevalence screening for ovarian cancer in postmenopausal women by CA-125 measurement and ultrasonography. Br Med J 306:1030 –1034, 1993 10. Bailey CL, Ueland FR, Land GL, DePriest PD, Gallion HH, Kryscio RJ, van Nagell JR: Malignant potential of small cystic ovarian tumors in women over 50 years of age. Gynecol Oncol 69:3–7, 1998