EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1978,8/4,187-193 @ Elsevier/North-Holland Biomedical Press
Age at menarche and menopause of uterine cancer patients J. de Graaff and L.A.M. Stoke Department
of Obstetrics and Gynecology,
Vrije Universiteit, Amsterdam,
___.
The Netherlands
-~
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DE GRAAFF, J. and STOLTE, L.A.M. (1978): Age at menarche and menopause of uterine cancer patients. Europ. J. Obstet. Gynec. reprod. Biol., 814, 187-193. An investigation was undertaken of the ages at menarche and at menopause of cervical and endometrial cancer patients for the years 1950-55 and 1960-65. Analysis of the ages at menarche in relation to the year of birth did not show a difference between the uterine cancer groups, whereas the age at menopause did show such a difference. The menopause occurred later in the endometrial than in the cervical cancer group. There was an earlier mean age at menarche and a later mean age at menopause per decade. Therefore, the menopause seems a constitutional factor involved in the development of endometrial cancer and perhaps also cervical cancer. epidemiology; cervical cancer; endometrial cancer
Doraiswami (1954) and Boyd and Doll (1964) found no difference between the mean age at menarche of cervical cancer patients and control women, nor did Wynder, Escher and Mantel (1966) or Trotnow and Pauli (1972) lind such a difference between endometrial cancer patients and control women. Lau, Petschalt, Poehls, Pollex, Unger and Zegenhagen (197.5) reported an earlier menarche in endometrial cancer patients compared with women out of the population. The ages at menopause have been occurring steadily later over the past 100 yr (Hauser, Remen, Valaer, Erb, Miiller and Obiri, 1963; Hofman and Soergel, 1972). The mean ages at menopause of cervical and endometrial cancer patients reported by several authors are shown in Table I. Wynder et al. (1966), Hauser, Miiller, Valaer, Erb, Obiri, Remen and Vanaanen (1961), Vahrson (1970) and Lau et al (1975) found a later menopause in endometrial cancer patients compared with control patients, while
Introduction
In the literature on cervical cancer and endometrial cancer the mean and median ages at menarche and at menopause are reported. However, a comparison between the ages at menarche and at menopause in both types of uterine cancer belonging to the same population is not available. It is well known that the age at menarche has been decreasing steadily over the past 100 yr. The rate of this diminution in age at menarche is calculated to be about 3-4 mth per decade (Van ‘t Land and De Haas, 1957; Hofman and Soergel, 1972;.Dann and Roberts, 1973; Huber, 1973). Contrary to Huber (1973) Dann and Roberts (1973) reported that the menarchhl age seemed to have stopped its downward trend in girls born about 1946 and thereafter. The mean ages at menarche of cervical and endometrial cancer patients reported by several authors are shown in Table I. Wynder, Cornfield, Schroff and 187
188 TABLE I
J. de Graaff and L.A.M. Stoke: Menarche and menopause in uterine cancer Mean ages at menarche and at menopause of cervical and endometrial cancer patients and control patients
Author(s)
Cancer
Menarche
Menopause
Cancer
Control
Cancer
Control
De Bruine (1954) Hauser et al. (1961) Boyd and Doll (1964) Vahrson (1970) Kuipers (1972)
Cervical Cervical Cervical Cervical Cervical
13.9 14.3 14.6
-
48.4 49.7
13.7 -
48.7 48.9
49.8 -
Hauser et al. (1961) Wynder et al. (1966) Vahrson (1970) Trotnow and Pauli (1972) Lau et al. (1975)
Endometrial Endometrial Endometrial Endometrial Endometrial
13.5 14.3 -
13.1 -
50.9 49.5 50.6 49.6 49.7
49.8 47.9 49.6 48.6
Baanders-van Halewijn (1962) and Trotnow and Pauli (1972) did not find such a difference. Hauser et al. (1961) reported no difference between the ages at menopause of cervical cancer patients and control women. In order to compare the ages at menarche and at menopause between cervical and endometrial cancer patients within the same population, the present study was undertaken. The ages at menarche and at menopause were obtained from the total number of women suffering from cervical and endometrial cancer in Rotterdam, The Netherlands, during two 5yr periods. Material and methods
The collection of the data of cervical and endometrial cancer patients during the periods 1950-55
TABLE II
Cancer
-
and 1960-65 is described by De Graaff and Stolte (1976). To obtain the data on menarche and menopause the recollection method was used. Such recall data are notoriously liable to error or bias from a variety of sources, but in a comparison of groups such errors are thought to be acceptable. The total number of cervical and endometrial cancer patients and the number of known dates of menarche and menopause are shown in Table II. The dates of menopause could of course only be obtained in the patients who developed cancer in the postmenopausal period. Statistical difference between two independent random variables was determined by the standard error of the difference; to detect a statistical change in age distribution, Student’s t-test was used, while the differences between sample variances were tested by the variance ratio test.
Number of cervical and endometrial cancer patients, number of patients with known ages at menarche and at menopause, and number of patients who are premenopausal Period
Patients
Menarche known
Menopause known
Premenopausal known
Menopause unknown
n
%
n
%
n
%
n
%
Cervical
1950-55 1960-65
371 497
273 404
73.6 81.3
157 242
42.3 48.7
153 207
41.2 41.6
61 48
16.5 9.7
Endometrial
1950-55 1960-65
193 282
108 172
56.0 61.0
109 187
56.5 66.3
28 27
14.5 9.6
56 68
29.0 24.1
J. de Graaff and LAN.
189
Stolte: Menarche and menopause in uterine cancer
Results In a previous study we reported the data on the age distribution and the mean age of the cervical and endometrial cancer patients (De Graaff and Stolte, 1976). The mean ages at menarche and at menopause of the uterine cancer patients are shown in Table III. In accordance with the literature it is clearly shown that the mean ages at menarche of both uterine cancers in the period 1960-65 are earlier than in the period 1950-55. The diminution for cervical and for endometrial cancer was 2.4 mth per decade. Statistical analysis did not show a significant difference between the mean ages at menarche of the two cervical cancer groups and between the two endometrial cancer groups, nor between the cervical and endometrial cancer groups of either period (P > 0.1). The mean ages at menopause in the period 196065 are later than in the period 1950-55 for the cervical and endometrial cancer groups. The percentage of cancer patients who were already postmeno-
TABLE III Cancer
Fig. 2. Mean ages at menopause of cervical and endometrial cancer patients of each 5-yr birth period.
pausal in the period 1960-65 at the onset of cancer was greater than in the period 1950-55, which can be explained by a later mean age in the period 196065. Statistical analysis did not show a significant difference between the mean ages at menopause of the two cervical cancer groups or between the two endometrial cancer groups (P > 0.1) but there is a significant difference between the cervical and endometrial cancer groups of 1950-55 and of 1960-65 (P < 0.01). Since there is a relationship between the year of birth and the age at menarche and menopause, the cancer patients were subdivided into 5-yr birth periods from 1865 to 1935. The number of patients in each birth period, the mean ages at menarche and at menopause and the standard deviations are shown in Table IV. There are no significant differences between the standard deviations at menarche and at menopause of both uterine cancers. Figure 1 shows the mean ages at menarche and Figure 2 the mean
Mean ages at menarche and at menopause of the cervical and endometrial cancer patients Period
Menarche
Menopause
n
Mean age
SD
n
Mean age
SD
Cervical
1950-55 1960-65
213 404
14.08 13.88
0.12 0.11
157 242
47.93 48.27
0.35 0.23
Endometrial
1950-5s 1960-65
108 112
14.24 14.03
0.19 0.12
109 187
49.52 49.86
0.41 0.32
n
5
13.80
Mean age
Cervical cancer
Menarche
1.634
SD
n 2 1
13.50 15.00
Mean age
Endometrial cancer
0.707 -
SD
n 1 7
54.00 47.85
Mean age
Cervical cancer
Menopause
2.117 1 .ooo
14.00 14.00
34 3
1925-29 1930-34
2.231 1.574
13.79 13.45
89 71
1915-19 1920-24
1.489 2.763 2.419 1.836 2.093 1.922 1.972 1.949
14.72 14.73 14.04 14.30 14.09 14.39 13.74 13.89
11 15 42 46 75 82 100 103
1875-79 1880-84 1885-89 1890-94 1895-99 1900-04 1905-09 1910-14
14.00 14.00
14.42 13.50
7 4 1 1
15.00 14.42 14.08 14.22 13.90 14.45 14.09 13.27
6 19 37 31 51 55 43 22
_
0.975 1.000
2.52,9 1.387 1.891 2.629 2.872 2.088 1.444 1.279 9 2
12 23 51 56 78 71 60 29 39.66 37.00
47.83 48.78 48.60 48.37 48.42 48.56 48.71 46.41
4.949 2.828
5.951 4.766 4.720 4.803 3.859 3.995 4.178 5.192
5.984
SD
46.00 26.00
1 1
47.50 51.00 50.55 50.96 49.16 49.74 50.16 50.00 49.30 49.00
2 2
Mean age
9 26 42 39 61 66 36 10
n
Endometrial cancer
-
4.126 3.605 4.005 3.499 4.282 4.634 3.592 6.514
3.535 1.414
SD
Number of cervical and endometrial cancer patients subdivided into S-yr birth periods with the mean ages at menarche and menopause and the standard deviations
____________________---_--_--_---_-__-___--__-__-__---_--_---__-_-__-____-----_--_-----__-_-_-__
1865-69 1870-74
Birth period
TABLE N
Q
.h
1865-69 1870-74 1875-79 1880-84 1885-89 1890-94 1895 -99 1900-04 1905-09 1910-14 1915-19 1920-24 _
Birth period
TABLE V
5 10 15 41 46 69 61 56 26 8 2
n
13.80 14.80 14.73 14.07 14.30 14.07 14.46 13.34 14.35 11.88 14.50
_
Mean age
SD _ 1.64 1.55 2.76 2.44 1.84 2.00 2.04 1.96 2.13 1.96 0.71
2 1 6 19 36 29 45 51 30 7 1 1
n 13.50 15.00 15.00 14.42 14.11 14.21 13.47 14.31 14.30 13.29 14.00 14.00
Mean age
SD 0.71 2.53 1.39 1.91 2.69 1.63 2.04 1.32 0.95 _ -
5 10 15 41 46 69 61 56 26 8 2
n 47.80 47.50 47.40 48.56 48.78 4858 48.52 48.59 46.31 39.25 37.00
Mean age
2 1 6 19 36 29 45 51 30 7 1 1
5.25 5.10 4.38 3.89 3.83 4.20 5.45 5.12 2.83
n
7.19 5.48
SD
50.41 49.17 49.29 46.00 26.00
49.19 49.31 SO.56
50.95
47.50 52.00 50.33
Mean age
cancer
and menopause
Endometrial
with the mean ages at menarche
cancer
Cervical
cancer
Cervical
Endometrial
Menopause
Menarche
cancer
Number of cervical and endometrial cancer patients subdivided into 5-yr birth periods, dard deviations, in whom both the ages at menarche and menopause were known
3.90 3.62 7.61 _ _
4.17 3.49 3.81
3.39
3.54 _ 5.09
SD
and the stan-
P g 2 E x B f 9 9 (P :: 2 ?
G % $ % (D s
192
J. de Graaff and L.A.M. Stolte: Menarche and menopause in uterine cancer
ages at menopause of each birth period of the cervical and endometrial cancer patients. It is clearly shown (Fig. 1) that there are no obvious differences in the mean ages at menarche of the cervical and endometrial cancer patients born between 1875 and 1924. The mean ages at menarche of the cervical and endometrial cancer patients born between 1875 and 1924 did not show a significant difference (Student’s t-tests, P > 0.05). The mean ages at menopause of the cervical and endometrial cancer patients born between 1875 and 1914 did, however, show a significant difference (P< 0.001) (Fig. 2). The endometrial cancer patients had a later menopause than the cervical cancer patients.
Discussion
In this study the mean age at menarche of the cervical and endometrial cancer patients occurred, in accordance with the literature, at an earlier age in the period 1960-65 than in the period 1950-55. There was no significant difference in the mean age at menarche between the cervical cancer groups and between the endometrial cancer groups, or between both cancer groups in the period 1950-55 and between both cancer groups in the period 1960-65. Vahrson (19 70) also found no difference in the mean age between patients developing cervical and endometrial cancer. Analysis of the ages at menarche in relation to the year of birth showed that there is no correlation between the age at menarche and cervical or endometrial cancer. In accordance with the dates reported in the literature, the mean age at menopause occurred later in the period 1960-65 than in the period 1950-55. There was no significant difference between the two cervical cancer groups and between the two endometrial cancer groups, but there was a difference between the cervical and endometrial cancer groups. This was reported by Hauser et al. (1961) and Vahrson (1970) who both also found that a later menopause occurred in patients with endometrial cancer than in patients with cervical cancer. Analysis of the ages at menopause in relation to the year of birth shows a consistent difference between the ages at menopause of the cancer groups. This demonstrates that there is a rela-
tionship between the age at menopause and cervical and/or endometrial cancer. The age at menopause of endometrial cancer patients can be later than normal, and that of cervical cancer patients earlier than normal. There is also the possibility that both are abnormal. Lau et al. (1975) have compared the ages at menarche and menopause of patients with endometrial cancer and a control group of the same age. They found that in these patients with endometrial cancer the menarche occurred significantly earlier than in the control group. Also, they noted that within each 5-yr birth period the menopause occurred significantly later than in the control group. Comparing these patients, in whom both the ages at menarche and menopause were known, with the whole group, the same trends were observed in subgroups in similar birth periods (Table V). This analysis further confirmed that there was no difference between the ages at menarche of both uterine cancer groups but a significant difference between the ages at menopause of both uterine cancer groups. Therefore, it appears that the menarche has no relation to the causation of cervical and endometrial cancer, but that the menopause is involved in the development of cervical and/ or endometrial cancer.
References Baanders-van Halewijn, E.A. (1962): Constitutionele en erfelijke aspecten van het endometrium carcinoom. Thesis, Utrecht. Boyd, J.T. and Doll, R. (1964): A study of the aetiology of carcinoma of the cervix uteri. Brit. J. Cancer, 18, 419. Dann, T.C. and Roberts, D.F. (1973): End of the trend? A 12-year study of age at menarche. Brit. med. J., 3, 265. De Bruine, T.L.A. (1954): De behandeling van carcinoma colli uteri. Thesis, Amsterdam. De Graaff, J. and Stolte, L.A.M. (1976): Trends in incidence rates of cervical and endometrial cancer. Europ. J. Obstet. Gynec. reprod. Biol., 5, 265. De Waard, F. and Van der Burg, A.T. (1966): Het tijdstip van de menopauze. Ned. T. Geneesk., 110, 289.
Hauser, G.A., Miiller, Th., Valaer, M., Erb, H., Obiri, J.A., Remen, U. and Vanlanen, P. (1961): Der Zusammenhang zwischen gynlkologischen Krankheiten und dem Menopausealter. Gynaecologia (Basel), 152, 270. Hauser, G.A., Remen, U., Valaer, M., Erb, H., Mtiller, Th. and Obiri, J. (1963): Menarche und Menopause in Israel. Gynaecologib (Base& 155, 39.
193
J. de Craaff and L.A.M. Stolte: Menarche and menopause in uterine cancer
Hofman, D. and Soergel, T. (1972): Untersuchungen iiber das Menarchen- und Menopausenalter. Geburtsh. u. Frauenheilk., 32, 969.
Huber,
A. (1973):
Zur Akzeleration
des Menarchealters.
Wien. klin. Wschr., 51, 844.
Jaszmann, L., Van Lith, N.D. and Zaat, J.C.A. (1969): The age at menopause in the Netherlands. Int. J. Fertil., 14, 106.
Kolk, J.J.
(1962):
De menarche
leeftijd.
Ned.
T
Sot.
Geneesk., 40, 645.
Kuipers, Th. (1972): Carcinoma of the uterine cervix. Aspects of clinical oncology in patients referred for radiation therapy. Acta radiol. (Stockh.), Suppl. 320. Lau, H.U., Petschalt, E., Poehls, H., Pollex, G., Unger, H.H.
and Zegenhagen, V. (1975): Epidemiologische Aspekte beim Korpuskarzinom. Zbl. Gyrzdk., 97, 1025. Trotnow, S. and Pauli, H.K. (1972): Zur Epidemiologie des Korpuskarzinoms. Arch. Gyntik., 213, 119. Vahrson, H. (1970): Umwelt und konstitutionelle Faktoren beim weiblichen Genitalkarzinom. Z. Geburtsh. Gyndk., 172,
94.
Van ‘t Land, G.M. and De Haas, J.H. (19757): Menarche leeftijd in Nederland. Ned. T. Geneesk., 101, 1425. Wynder, E.L., Cornfield, J., Schroff, P.D. and Doraiswami, K.R. (1954): A study of environmental factors in carcinoma of the cervix. Amer. J. Obstet. Gynec. 68, 106. Wynder, E.L., Escher, G C. and Mantel, N. (1966): An epidemiological investigation of cancer of the endometrium. Cancer (Philad.), 19, 489.