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Progesterone challenge test and estrogen assays in menopausal women with endometrial adenomatous hyperplasia
Int. J. Gynecol. Obstet.. 1988, 26: 115-l 19 International Federation of Gynecology & Obstetrics
115
Progesterone challenge test and estrogen assays in menopausal women with endometrial adenomatous hyperplasia M.K. Toppozadaa, A. EL-Farasc
A.A.A.
Ismaib, R.S.M. Hameda, K. Sid Ahmedb and
aDepartment of Obstetrics and Gynecology, bDepartment of Pathology, Alexandria University and cDepartment of Physiology, Medical Research Institute, Alexandria (Egypt) (Received January 12th, 1987) (Revised and accepted April lst, 1987)
Abstract In an attempt to detect asymptomatic endometrial adenomatous hyperplasia in postmenopausal women, 40 cases were subjected to progesterone challenge test (PCT), measurement of serum estrogen and endometrial curettage. Group A (n = 30) included postmenopausal asymptomatic women, while group B (control group; n = 10) were cases with adenomatous hyperplasia (AH) diagnosed by biopsy. PCT showed a 100% sensitivity, 92% specificity, 71.4% predictive value of a positive test and 100% predictive value of a negative test in the detection of AH. Mean serum concentrations of E, and Ez were significantly higher in patients with AH compared to cases with other endometrial histologies. Serum E, and E, and PCT can be used as screening tests to identify postmenopausal women with endometrial AH and thus at a greater risk of developing carcinoma. Endometrial Keywords: adenomatus hyperplasia; progesterone challenge test; Estrogen assays in menopause. Introduction Currently,
there is no convenient,
inex-
0020-7292/88/$03.50 0 1988 International Federation of Gynecology&Obstetrics Published and Printed in Ireland
pensive screening test for the detection of postmenopausal women at risk for developing endometrial adenocarcinoma. AH, the most frequently encountered form of endometrial precancerous lesions, may be symptomatic leadng to uterine bleeding or may remain asymptomatic and proceed unnoticed to adenocarcinoma [8]. AH was found to be present in 10% of asymptomatic postmenopausal women [6,9]. The clinical research concerning the early detection of adenocarcinoma of the uterus has focused on identifying women at risk and using sampling devices applicable to mass screening. As regards women at high risk, there are many factors implicated [7,13], the most important of which is estrogen, either exogenous [2,10] or endogenous 141. Mass screening of asymptomatic women in diagnosing endometrial was poor adenocarcinoma using Papanicolaou smear. Moreover, such a smear has no role in identifying hyperplasia [3]. Detection rates of adenocarcinoma and AH reached 90% using Novak currette 191, and up to 100% using Bavra aspirator [I]. However, the routine use of endometrial biopsy or Vabra aspirator in truly asymptomatic postmenopausal women has not been widely accepted because of patient discomfort and relatively low yield. Clinical and Clinical Research Article
116
Toppozada et al.
The aim of this work was to assess: (a) the sensitivity and reliability of PCT in the detection of AH in postmenopausal women who would thus be at a higher risk for the development of endometrial carcinoma; (b) the value of serum estrogen level as a screening test in identifying postmenopausal women at risk for the development of AH. Materials and methods This study was carried out on two groups: Group A, 30 postmenopausal women chosen from the outpatient clinic of the Shatby Maternity University Hospital; Group B, 10 perimenopausal or postmenopausal women with AH diagnosed by biopsy to serve as a control group. All the women in group A fulfilled the following criteria: they were (I) postmenopausal for at least 2 years, none had postmenopausal bleeding; (2) they were not under any hormonal treatment since the onset of menopause; (3) normal clinical pelvic examination. All the cases (Groups A and B) were subjected to: (1) full record of history with special regard to the age of menarche, age of menopause, parity, diabetes mellitus, hypertension, usage of any contraceptive methods in the fertile period and family history of cancer of the body of the uterus; (2) full clinical examination. All the women in group A were subjected to the following studies. Histopathological study Using a Novak curette, the endometrial tissue obtained was preserved in 10% formalin solution. The specimen was then processed, fixed in wax blocks, cut into fine sections, and finally stained with haematoxylin and eosin before being examined by an expert pathologist. Hormonal study A blood sample (about 2 ml) was taken from the antecubital vein, left to clot and then centrifuged to obtain serum for the esInt J Gynecol Obstet 26
timation of estrogens (estradiol, estrone and estriol by radioimmunoassay [ 111. Progesterone challenge test All the women were given 100 mg progesterone in oily solution intramascularly in the gluteal region. The patients were asked to return 2 weeks later to record any form of withdrawal bleeding with special reference to its onset and duration. Each patient was informed about the normal spotting which would occur for about 2-3 days following curettage. In the control Group B, the patients were subjected to the same procedures except for the endometrial biopsy. Student’s t-test was used to detect any significant difference in estrogen concentration. Results The results obtained as follows:-
from the study were
Group A: asymptomatic postmenopausal women (n = 30) Clinical data. The mean age was 51.9 f 4.2 years. The mean postmenopausal duration was 5.6 f 1.7 years. The parity was high except for one case who was a primipara and another who was a nulligravida. Obesity was found in 20% (n = 6), hypertension in 23.3% (n = 7) and diabetes mellitus in 10% (n = 3). The clinical presentation was in the form of leukorrhea (53.3%, n = 16), backache (23.3%, n = 7), cystocele (10070, n = 3) vulvitis (7Or0, n = 2), stress incontinence (3.3%) n = 1) or labial abscess (3.3070, n = 1). Histopathological data. The histopathological results of the endometrial biopsies taken by Novak curette are shown in Table I. Five cases showed AH (16.6%). When the AH group was compared with the other cases, no significant difference was found regarding postmenopausal parity, age, duration, obesity, hypertension or diabetes mellitus.
Progesterone test and estrogen assay in menopause Endometrial Table I. postmenopausal women Histological
patterns
histology (Group A).
of
the endometrium 1 2 3 4 5
Normal endometrium (proliferative) Atrophic endometrium Atrophic endometrium with retrogressed cystic hyperplasia Senile endometritis Adenomatous hyperplasia
in
30
No. of
Per-
cases
centage
9 13
30.3 43.3
2 1 5
6.7 3.3 16.6
30
Total
asymptomatic
100
Hormonal data. The mean serum estrogen (E,, E, and EJ concentrations in cases with AH and those showing other histologies are presented in Table II. There was a elevation in E, significant and E, concentrations (P < 0.01) in cases with AH compared to cases with other endometrial histologies. Progesterone challenge test results. Out 30 asymptomatic of postmenopausal women, only 7 cases showed withdrawal uterine bleeding following progesterone injection. Five out of the 7 cases proved to have endometrial AH. The bleeding occurred 5-7 days following progesterone injection and its duration ranged from 1 to 4 days. Of the remaining two cases, one showed proliferative endometrium and the other atrophic endometrium with retro-
Comparison between the mean serum levels Table 11. (-t SD.) of estrone, estradiol and estriol in patients with AH and those with other histologies (Group A). Estrogen
Adenomatous (n = 5)
Estrone (rig/ml) Estradiol (pg/ml) Estriol
(ng/ml)
%ignificant
0.13 (0.04) 27.8 (12.15) 0.27 (0.16)
Nonadenomatous (n = 25) 0.08 (0.03)a 16.56 (6.7lP 0.?3 (0.19)
Table III. The sensitivity, specificity and predictive of the PCT in the diagnosis of AH (Group A).a Screening parameter
Cases with AH
Cases with other histologies
Bleeding No bleeding
5 -
2 23
117 value
aSensitivity 515 (100%); specificity 23125 (92%); predictive value of positive test 517 (71.4Vo); Predictive value of negative test 23/23
(100%).
gressed cystic hyperplasia. Table III shows the sensitivity, specificity and predictive value of positive and negative PCT tests. All the cases in the group with AH showed withdrawal uterine bleeding following PCT, i.e. none of the cases who did not exhibit withdrawal bleeding proved to have AH. This means that the reliability of a negative test is 100%. However, the test was only 92% specific since 2 cases with other histologies exhibited withdrawal bleeding and the reliability of a positive test was only 71.4%. Group B: symptomatic perimenopausal or postmenopausal women with AH (control group, n = 10) Clinical data. The mean age was 50.3 +2.1 years. All the cases presented clinically with uterine bleeding. No significant difference was found between the clinical data in this group compared to Group A. Histopathological data. All the cases proved to have AH using endometrial curettage as biopsy. Hormonal data. Table IV shows the Comparison between the mean,serum levels of Table IV. estrogens (E,, E,, Es) in the asymptomatic and symptomatic cases of AH, showing similar values (P > 0.05). Estrogen
Asymptomatic AH (n = 5)
Symptomatic AH (n = 10)
BI (ngjml) EZ (pg/ml) E3 (nglml)
0.13 27.80 0.27
0.16 2 0.02 29.20 r 8.16 0.23 k 0.08
* 0.04 k 12.15 k 0.16
(P < 0.01).
Clinical and Clinical Research Article
118
Toppozada et al.
mean (f S.D.) serum E,, E, and E, concentrations in symptomatic (Group B, n = 10) and asymptomatic (Group A, n = 5) cases of AH. There was no significant difference between the mean serum levels of estrogens in both groups. Progesterone challenge test results. All the cases in this group experienced an episode of withdrawal uterine bleeding ranging from 3 to 5 days following progesterone injection. The bleeding occurred 7-10 days following injection. Discussion Early detection of endometrial carcinoma has been the subject of continuous research [1,2,3,10]. However, up till now there has been no, non-invasive, inexpensive and reliable test to fulfil that purpose. In the present study the PCT was 100% sensitive, i.e. no case of AH would be missed following the PCT. The reliability of the negative test was 1OOVowhich means that cases exhibiting uterine bleeding which do not respond to the PCT should be considered free of AH. However, reliability of a positive test was only 71.4% since two cases without AH exhibited withdrawal bleeding. On the other hand all the control cases (n = 10) with symptomatic AH exhibited withdrawal bleeding following PCT which confirms the results of the asymptomatic group. These results agree with the results of Hanna et al. [6] who reported that in postmenopausal women responding to progesterone injection by withdrawal bleeding, AH was not necessarily the reason, since it presented in 3 out of 5 cases who showed withdrawal bleeding. Moreover, Gambrel1 et al. [5] conducted a study using Provera (10 mg for 10 days) given to postmenopausal women treated with exogenous estrogens or having high endogenous estrogens. They recommended continuous treatment with progesterone for 6 months in cases showing Int J Gynecol Obstet 26
withdrawal bleeding followed by hysterectomy if withdrawal bleeding continues. In the present study cases using exogenous estrogens were excluded. Serum levels of estrone (I!!,) and estradiol (E,) were found to be significantly higher in patients with AH compared to those with other histologies. There was no significant difference between serum estriol (E,) in both groups. It is well known that EJ competes with E, for the cytoplasmic binding sites in cells from estrogen target organs and markedly inhibits E, incorporation by the nuclei of chemically-induced rat breast tumors [ 121. Therefore, thb normal level of E, detected in the present study together with high levels of E, and E, may indicate a certain pattern of hormonal imbalance as regards the ratio of E/E, and E,. This may be an important factor in cases with AH. There was no significant difference between the mean serum estrogens in both asymptomatic and symptomatic groups of AH. This could be explained by differences in estrogen thresholds in different individuals or lack of fluctuations in estrogen concentrations in asymptomatic subjects. The high levels of E, and E, concentration detected in cases of AH in the present study supports the previously published data emphasising the importance of estrogens (exogenous or endogenous) as one of the high risk factors in the etiology of AH and/ adenocarcinomas in endometrial or postmenopausal women [2,4, lo]. From the previous data the following conclusions can be made. (1) Ser.um E, and E, concentrations can be used as a screening test to identify postmenopausal women at risk for the development of endometrial AH. However, there are no fixed levels of these hormones that can be utilized with a reasonable degree of accuracy to indicate whether AH exists or not. (2) PCT is a sensitive but not completely reliable test in the detection of
Progesterone test and estrogen assay in menopause
postmenopausal women with AH who thus may be at risk for developing endometrial adenocarcinoma. A positive test (occurrence of bleeding) is a suggestive indication for the existence of AH and hence the risk for developing adenocarcinoma, while a negative test is a good reassuring sign for its absence. The PCT, however, is a simple, clinical, non-expensive test, and applicable when hormone assay facilities are lacking. It is recommended to subject each postmenopausal woman to PCT. Those who exhibit withdrawal bleeding should be followed up by endometrial currettage and histopathological examination. References Creasman WT, Weed JC: Screening techniques in endometrial cancer. Cancer 38: 436, 1976. Davis JL, Rosenstein NB, Antunes MF, Stolley PD: A review of risk factors for endometrial carcinoma. Obstet Gynecol36: 107, 1981. Disaia PJ, Creasman WT: Clinical Gynecologic Onology, Mosby Company, St Louis, 1981. Gambrel1 RD: The role of hormones in endometrial cancer. South Med J 71: 1280, 1978. Gambrel1 RD: Preventing endometrial cancer with progestin. Contrib Obstet Gynecol 17: 133, 1981. Hanna JH, Brady WK, Hill JM, Phillips CL: Detection of post-menopausal women at risk for endometrial can-
7
8
119
cinema by a progesterone challenge test: Am J Obstet Gynecol 147(8): 872, 1983. Kistner RW, Krantz KF, Lebherz TB: Endometrial cancer: rising incidence, detection and treatment. J Reprod Med IO: 53, 1973. Scully RE: Definition of endometrial carcinoma precursors. Clin Obstet Gynecol25(I): 39, 1982. Simsen DA, Shirts SR, Howard FM, Sims J, Hill JM: Endometrial findings in asymptomatic postmenopausal women on exogenous estrogens. Gynecol Oncol 11: 56,
1981. Smith DC, Prentice R, Thompson exogenous estrogen and endometrial
DJ: Association of carcinoma. N Engl
J Med 293: 1164, 1975. WHO Special Programme of Research, Development and Research Training in Human Reproduction: Estrogen Assay, 6th edn, 1982. Wotiz HH, Shone JA, Vigersky R, Brecher PI: The regulatory role of estriol in the proliferative action of estradiol. In Prognostic Factors in Breast Cancer (ed APM Forrest, PB Kunkler), p. 368. Livingstone, Edinburgh and London, 1968. Wynder EL, Esher GG, Mantle N: An epidemiological investigation of cancer of the endometrium. Cancer 19: 498, 1966.
Address for reprints: M.K. Toppozoda, M.D. Department of Obstetrics and Gynecology Sbatby Hospital Alexandria Egypt
Clinical and Clinical Research Article
115
Progesterone challenge test and estrogen assays in menopausal women with endometrial adenomatous hyperplasia M.K. Toppozadaa, A. EL-Farasc
A.A.A.
Ismaib, R.S.M. Hameda, K. Sid Ahmedb and
aDepartment of Obstetrics and Gynecology, bDepartment of Pathology, Alexandria University and cDepartment of Physiology, Medical Research Institute, Alexandria (Egypt) (Received January 12th, 1987) (Revised and accepted April lst, 1987)
Abstract In an attempt to detect asymptomatic endometrial adenomatous hyperplasia in postmenopausal women, 40 cases were subjected to progesterone challenge test (PCT), measurement of serum estrogen and endometrial curettage. Group A (n = 30) included postmenopausal asymptomatic women, while group B (control group; n = 10) were cases with adenomatous hyperplasia (AH) diagnosed by biopsy. PCT showed a 100% sensitivity, 92% specificity, 71.4% predictive value of a positive test and 100% predictive value of a negative test in the detection of AH. Mean serum concentrations of E, and Ez were significantly higher in patients with AH compared to cases with other endometrial histologies. Serum E, and E, and PCT can be used as screening tests to identify postmenopausal women with endometrial AH and thus at a greater risk of developing carcinoma. Endometrial Keywords: adenomatus hyperplasia; progesterone challenge test; Estrogen assays in menopause. Introduction Currently,
there is no convenient,
inex-
0020-7292/88/$03.50 0 1988 International Federation of Gynecology&Obstetrics Published and Printed in Ireland
pensive screening test for the detection of postmenopausal women at risk for developing endometrial adenocarcinoma. AH, the most frequently encountered form of endometrial precancerous lesions, may be symptomatic leadng to uterine bleeding or may remain asymptomatic and proceed unnoticed to adenocarcinoma [8]. AH was found to be present in 10% of asymptomatic postmenopausal women [6,9]. The clinical research concerning the early detection of adenocarcinoma of the uterus has focused on identifying women at risk and using sampling devices applicable to mass screening. As regards women at high risk, there are many factors implicated [7,13], the most important of which is estrogen, either exogenous [2,10] or endogenous 141. Mass screening of asymptomatic women in diagnosing endometrial was poor adenocarcinoma using Papanicolaou smear. Moreover, such a smear has no role in identifying hyperplasia [3]. Detection rates of adenocarcinoma and AH reached 90% using Novak currette 191, and up to 100% using Bavra aspirator [I]. However, the routine use of endometrial biopsy or Vabra aspirator in truly asymptomatic postmenopausal women has not been widely accepted because of patient discomfort and relatively low yield. Clinical and Clinical Research Article
116
Toppozada et al.
The aim of this work was to assess: (a) the sensitivity and reliability of PCT in the detection of AH in postmenopausal women who would thus be at a higher risk for the development of endometrial carcinoma; (b) the value of serum estrogen level as a screening test in identifying postmenopausal women at risk for the development of AH. Materials and methods This study was carried out on two groups: Group A, 30 postmenopausal women chosen from the outpatient clinic of the Shatby Maternity University Hospital; Group B, 10 perimenopausal or postmenopausal women with AH diagnosed by biopsy to serve as a control group. All the women in group A fulfilled the following criteria: they were (I) postmenopausal for at least 2 years, none had postmenopausal bleeding; (2) they were not under any hormonal treatment since the onset of menopause; (3) normal clinical pelvic examination. All the cases (Groups A and B) were subjected to: (1) full record of history with special regard to the age of menarche, age of menopause, parity, diabetes mellitus, hypertension, usage of any contraceptive methods in the fertile period and family history of cancer of the body of the uterus; (2) full clinical examination. All the women in group A were subjected to the following studies. Histopathological study Using a Novak curette, the endometrial tissue obtained was preserved in 10% formalin solution. The specimen was then processed, fixed in wax blocks, cut into fine sections, and finally stained with haematoxylin and eosin before being examined by an expert pathologist. Hormonal study A blood sample (about 2 ml) was taken from the antecubital vein, left to clot and then centrifuged to obtain serum for the esInt J Gynecol Obstet 26
timation of estrogens (estradiol, estrone and estriol by radioimmunoassay [ 111. Progesterone challenge test All the women were given 100 mg progesterone in oily solution intramascularly in the gluteal region. The patients were asked to return 2 weeks later to record any form of withdrawal bleeding with special reference to its onset and duration. Each patient was informed about the normal spotting which would occur for about 2-3 days following curettage. In the control Group B, the patients were subjected to the same procedures except for the endometrial biopsy. Student’s t-test was used to detect any significant difference in estrogen concentration. Results The results obtained as follows:-
from the study were
Group A: asymptomatic postmenopausal women (n = 30) Clinical data. The mean age was 51.9 f 4.2 years. The mean postmenopausal duration was 5.6 f 1.7 years. The parity was high except for one case who was a primipara and another who was a nulligravida. Obesity was found in 20% (n = 6), hypertension in 23.3% (n = 7) and diabetes mellitus in 10% (n = 3). The clinical presentation was in the form of leukorrhea (53.3%, n = 16), backache (23.3%, n = 7), cystocele (10070, n = 3) vulvitis (7Or0, n = 2), stress incontinence (3.3%) n = 1) or labial abscess (3.3070, n = 1). Histopathological data. The histopathological results of the endometrial biopsies taken by Novak curette are shown in Table I. Five cases showed AH (16.6%). When the AH group was compared with the other cases, no significant difference was found regarding postmenopausal parity, age, duration, obesity, hypertension or diabetes mellitus.
Progesterone test and estrogen assay in menopause Endometrial Table I. postmenopausal women Histological
patterns
histology (Group A).
of
the endometrium 1 2 3 4 5
Normal endometrium (proliferative) Atrophic endometrium Atrophic endometrium with retrogressed cystic hyperplasia Senile endometritis Adenomatous hyperplasia
in
30
No. of
Per-
cases
centage
9 13
30.3 43.3
2 1 5
6.7 3.3 16.6
30
Total
asymptomatic
100
Hormonal data. The mean serum estrogen (E,, E, and EJ concentrations in cases with AH and those showing other histologies are presented in Table II. There was a elevation in E, significant and E, concentrations (P < 0.01) in cases with AH compared to cases with other endometrial histologies. Progesterone challenge test results. Out 30 asymptomatic of postmenopausal women, only 7 cases showed withdrawal uterine bleeding following progesterone injection. Five out of the 7 cases proved to have endometrial AH. The bleeding occurred 5-7 days following progesterone injection and its duration ranged from 1 to 4 days. Of the remaining two cases, one showed proliferative endometrium and the other atrophic endometrium with retro-
Comparison between the mean serum levels Table 11. (-t SD.) of estrone, estradiol and estriol in patients with AH and those with other histologies (Group A). Estrogen
Adenomatous (n = 5)
Estrone (rig/ml) Estradiol (pg/ml) Estriol
(ng/ml)
%ignificant
0.13 (0.04) 27.8 (12.15) 0.27 (0.16)
Nonadenomatous (n = 25) 0.08 (0.03)a 16.56 (6.7lP 0.?3 (0.19)
Table III. The sensitivity, specificity and predictive of the PCT in the diagnosis of AH (Group A).a Screening parameter
Cases with AH
Cases with other histologies
Bleeding No bleeding
5 -
2 23
117 value
aSensitivity 515 (100%); specificity 23125 (92%); predictive value of positive test 517 (71.4Vo); Predictive value of negative test 23/23
(100%).
gressed cystic hyperplasia. Table III shows the sensitivity, specificity and predictive value of positive and negative PCT tests. All the cases in the group with AH showed withdrawal uterine bleeding following PCT, i.e. none of the cases who did not exhibit withdrawal bleeding proved to have AH. This means that the reliability of a negative test is 100%. However, the test was only 92% specific since 2 cases with other histologies exhibited withdrawal bleeding and the reliability of a positive test was only 71.4%. Group B: symptomatic perimenopausal or postmenopausal women with AH (control group, n = 10) Clinical data. The mean age was 50.3 +2.1 years. All the cases presented clinically with uterine bleeding. No significant difference was found between the clinical data in this group compared to Group A. Histopathological data. All the cases proved to have AH using endometrial curettage as biopsy. Hormonal data. Table IV shows the Comparison between the mean,serum levels of Table IV. estrogens (E,, E,, Es) in the asymptomatic and symptomatic cases of AH, showing similar values (P > 0.05). Estrogen
Asymptomatic AH (n = 5)
Symptomatic AH (n = 10)
BI (ngjml) EZ (pg/ml) E3 (nglml)
0.13 27.80 0.27
0.16 2 0.02 29.20 r 8.16 0.23 k 0.08
* 0.04 k 12.15 k 0.16
(P < 0.01).
Clinical and Clinical Research Article
118
Toppozada et al.
mean (f S.D.) serum E,, E, and E, concentrations in symptomatic (Group B, n = 10) and asymptomatic (Group A, n = 5) cases of AH. There was no significant difference between the mean serum levels of estrogens in both groups. Progesterone challenge test results. All the cases in this group experienced an episode of withdrawal uterine bleeding ranging from 3 to 5 days following progesterone injection. The bleeding occurred 7-10 days following injection. Discussion Early detection of endometrial carcinoma has been the subject of continuous research [1,2,3,10]. However, up till now there has been no, non-invasive, inexpensive and reliable test to fulfil that purpose. In the present study the PCT was 100% sensitive, i.e. no case of AH would be missed following the PCT. The reliability of the negative test was 1OOVowhich means that cases exhibiting uterine bleeding which do not respond to the PCT should be considered free of AH. However, reliability of a positive test was only 71.4% since two cases without AH exhibited withdrawal bleeding. On the other hand all the control cases (n = 10) with symptomatic AH exhibited withdrawal bleeding following PCT which confirms the results of the asymptomatic group. These results agree with the results of Hanna et al. [6] who reported that in postmenopausal women responding to progesterone injection by withdrawal bleeding, AH was not necessarily the reason, since it presented in 3 out of 5 cases who showed withdrawal bleeding. Moreover, Gambrel1 et al. [5] conducted a study using Provera (10 mg for 10 days) given to postmenopausal women treated with exogenous estrogens or having high endogenous estrogens. They recommended continuous treatment with progesterone for 6 months in cases showing Int J Gynecol Obstet 26
withdrawal bleeding followed by hysterectomy if withdrawal bleeding continues. In the present study cases using exogenous estrogens were excluded. Serum levels of estrone (I!!,) and estradiol (E,) were found to be significantly higher in patients with AH compared to those with other histologies. There was no significant difference between serum estriol (E,) in both groups. It is well known that EJ competes with E, for the cytoplasmic binding sites in cells from estrogen target organs and markedly inhibits E, incorporation by the nuclei of chemically-induced rat breast tumors [ 121. Therefore, thb normal level of E, detected in the present study together with high levels of E, and E, may indicate a certain pattern of hormonal imbalance as regards the ratio of E/E, and E,. This may be an important factor in cases with AH. There was no significant difference between the mean serum estrogens in both asymptomatic and symptomatic groups of AH. This could be explained by differences in estrogen thresholds in different individuals or lack of fluctuations in estrogen concentrations in asymptomatic subjects. The high levels of E, and E, concentration detected in cases of AH in the present study supports the previously published data emphasising the importance of estrogens (exogenous or endogenous) as one of the high risk factors in the etiology of AH and/ adenocarcinomas in endometrial or postmenopausal women [2,4, lo]. From the previous data the following conclusions can be made. (1) Ser.um E, and E, concentrations can be used as a screening test to identify postmenopausal women at risk for the development of endometrial AH. However, there are no fixed levels of these hormones that can be utilized with a reasonable degree of accuracy to indicate whether AH exists or not. (2) PCT is a sensitive but not completely reliable test in the detection of
Progesterone test and estrogen assay in menopause
postmenopausal women with AH who thus may be at risk for developing endometrial adenocarcinoma. A positive test (occurrence of bleeding) is a suggestive indication for the existence of AH and hence the risk for developing adenocarcinoma, while a negative test is a good reassuring sign for its absence. The PCT, however, is a simple, clinical, non-expensive test, and applicable when hormone assay facilities are lacking. It is recommended to subject each postmenopausal woman to PCT. Those who exhibit withdrawal bleeding should be followed up by endometrial currettage and histopathological examination. References Creasman WT, Weed JC: Screening techniques in endometrial cancer. Cancer 38: 436, 1976. Davis JL, Rosenstein NB, Antunes MF, Stolley PD: A review of risk factors for endometrial carcinoma. Obstet Gynecol36: 107, 1981. Disaia PJ, Creasman WT: Clinical Gynecologic Onology, Mosby Company, St Louis, 1981. Gambrel1 RD: The role of hormones in endometrial cancer. South Med J 71: 1280, 1978. Gambrel1 RD: Preventing endometrial cancer with progestin. Contrib Obstet Gynecol 17: 133, 1981. Hanna JH, Brady WK, Hill JM, Phillips CL: Detection of post-menopausal women at risk for endometrial can-
7
8
119
cinema by a progesterone challenge test: Am J Obstet Gynecol 147(8): 872, 1983. Kistner RW, Krantz KF, Lebherz TB: Endometrial cancer: rising incidence, detection and treatment. J Reprod Med IO: 53, 1973. Scully RE: Definition of endometrial carcinoma precursors. Clin Obstet Gynecol25(I): 39, 1982. Simsen DA, Shirts SR, Howard FM, Sims J, Hill JM: Endometrial findings in asymptomatic postmenopausal women on exogenous estrogens. Gynecol Oncol 11: 56,
1981. Smith DC, Prentice R, Thompson exogenous estrogen and endometrial
DJ: Association of carcinoma. N Engl
J Med 293: 1164, 1975. WHO Special Programme of Research, Development and Research Training in Human Reproduction: Estrogen Assay, 6th edn, 1982. Wotiz HH, Shone JA, Vigersky R, Brecher PI: The regulatory role of estriol in the proliferative action of estradiol. In Prognostic Factors in Breast Cancer (ed APM Forrest, PB Kunkler), p. 368. Livingstone, Edinburgh and London, 1968. Wynder EL, Esher GG, Mantle N: An epidemiological investigation of cancer of the endometrium. Cancer 19: 498, 1966.
Address for reprints: M.K. Toppozoda, M.D. Department of Obstetrics and Gynecology Sbatby Hospital Alexandria Egypt
Clinical and Clinical Research Article