The Effect of Age upon the Pattern of the Menstrual Cycle. Mary E. Collett, Ph.D., Grace E. Wertenberger, Ph.D., and Virginia M. Fiske, Ph.D.

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1 The Effect of Age upon the Pattern of the Menstrual Cycle Mary E. Collett, Ph.D., Grace E. Wertenberger, Ph.D., and Virginia M. Fiske, Ph.D. THERE IS considerable information in the literature on the pattern of the menstrual cycle in adult women, but little as to the effect of age upon the pattern.2, 4, 5, 19,22,32,43 It is known in a general way that during adolescence and at the menopause cycle length is subject to wider variation than between 20 and 40 years and that anovulatory cycles are more frequent, but further details are lacking. In the years of maturity ovulation is variable but generally falls between the Days 12 and 16. The luteal phase also varies, though somewhat less than the follicular phase. The frequency of anovulatory cycles is variously reported as 2-25 per cent in normal women and from 12 per cent to over 50 per cent in the relatively sterile. 3, 19, 21, 25, 28, 35, 40, 44 It would therefore seem worth while to examine the menstrual pattern at various ages in some detail. Several means of identifying the day of ovulation have been used. Most are open to some objection. 2 Generally the day of ovulation, as determined by whatever method, falls close to the low point of the basal temperature curve, although it may not coincide with it exactly (Table 1).42 METHOD AND MATERIALS We have chosen the basal temperature curve as a useful index of ovarian From the Department of Biology, Western Reserve University, Cleveland, Ohio (M.E.C.); the Department of Physiology, Indiana University, Bloomington, Indiana (G.E.W.); and the Department of Zoology and Physiology, Wellesley College, Wellesley, Massachusetts (U.M.F.). This work has been aided by grants from Western Reserve University, Indiana University, and Wellesley College. 437

2 438 COLLETT ET AL. Fertility & Sterility activity because it differentiates between ovulatory and anovulatory cycles and indicates the duration and efficiency of the luteal phase, even though it does not date the day of ovulation precisely. The temperature was taken orally, fasting and before rising, and so far as possible at the same hour each day. Our subjects were students and staff members, chiefly unmarried, at our respective institutions. We are indebted to Miss Marylin Morrow of the Dept. of Physiology at Mount Holyoke College for one series of 10 con- TABLE 1. Ovulation as Related to the Low Point of the Basal Temperature Curve According to method and cited literature Assay Rat test Biopsy Method Cervical mucus Vaginal smear Mittelschmerz Inspection Culdoscope13 Time of ovulation Before L. p.a At L. P. Bergman;5 D'Amourll; Bergman; D'Amour; Rogers & Sturgis36 Rogers & Sturgis Farris (41%) 17 Farris (15%) Bergman (11%); 5 Bergman (47%); D'Amour;l1 Davis;12 D'Amour; Buxton Buxton & Engle7 & Engle Pommerenke & Viergiver33 Diddle;14 Vollmann (11%) 43 Isolated coitus or Farris;11 Doring;15 artif.insemination Franken;18 Siegler & Siegler39 a L. P. = low point on basal temperature curve. Pommerenke & Viergiver Diddle; Vollmann (26%) Greulich20 Doyle16 Abarbanel;l Farris; Doring; Franken; Siegler & Siegler; Jackson27 After L. P. Bergman; D'Amour; Rogers & Sturgis; Roth & Berger37 Farris (42%) Bergman (42%); D'Amour; Buxton & Engle Pommerenke & Viergiver Roth & Berger;37 Rubinstein;38 Davis12 Vollmann (63%) Greulich Doyle Farris; Doring; Franken; Siegler & Siegler secutive cycles from the same subject. We present 302 complete cycles (B.T. or B.M.R.) from 146 women between the ages of 17 and 50, plus a varying number of incomplete cycles. We have divided the subjects into 5-year age groups, except for the first group (17-19) and the last (40-50). We have considered the low point just before the sustained luteal rise in temperature as the day of ovulation. Each graph was analyzed for cycle length, duration of menses, day of ovulation, and length and character of

3 Vol. 5, No.5, 1954 MENSTRUAL CYCLE AND AGE 439 the luteal phase. The original B.T. and B.M.R. curves are being privately printed and copies may be had upon request. RESULTS Cycle Length Length of cycle was variable at all ages (16-92 days for the series as a whole), but the range was wider at years and years than at TABLE 2. Length of Menstrual Cycle Length of cycle in days Age Range Mode Mean (Yr. ) No. Cycles (da. ) (da. ) (cia. ) All ages intermediate ages (Table 2, Fig. 1). The median was close to the traditional 28 days at all ages. The mode fell from 30 days in the youngest group to 25 days in the oldest. The mean length of the cycle fell with increasing age from years as has been found previously The drop in mean TABLE 3. Shift in Cycle Length at the Menopause 178 cycles from one subject Length of cycle in days Age length was especially striking at years. An intermingling of very short and very long cycles occurred both at the menopause and in adolescence. The menopausal change is illustrated in the following summary of the record of one subject, previously reported in detail. 9 In this subject 55 per cent of the cycles before 50 were days as compared with only 26 per cent after 50. (Table 3.)

4 440 COLLETT ET AL. Fertility & Sterility Fig. 1. Distribution of B.T. or B.M.T. records in regard to cycle length and related factors. Length of Menses We observed a range of 2-9 days in the duration of the menses (Table 4, Fig. 1). Both mean and mode were close to 5 days at all ages. Between 35 and 50 years we found fewer long menses (over 7 days) than earlier. An overwhelming proportion of the cycles ( per cent) showed menses of 3-7 days at all ages, and per cent fell within 3-5 days. This agrees with previous observations Anovulatory Cycles The highest proportion of anovulatory cycles (30.8 per cent) occurred at years. The percentage was fairly high at 20-24, , and 40-50

5 Vol. 5, No.5, 1954 MENSTRUAL CYCLE AND AGE 441 TABLE 4. Duration of Menses Duration in days Age Range Mode Mean (Yr.) No. Cycles (da.) ( da.) (da. ) II All ages years (9.8 per cent, 12 per cent, and 15 per cent respectively) (Table 5, Fig. 1). Between 25 and 34 years the percentage was much lower and was close to the 2.5 per cent observed by Goldzieher et al., the majority of whose subjects were in this age range. Day of Ovulation We have arbitrarily considered the low point just before the sustained rise in temperature as the day of ovulation. As we have dated it, ovulation TABLE 5. Incidence of Anovulatory Cycles Age Anovulatory cycles (Yr.) No. Cycles No. % II II All ages occurred anywhere from the Day 4 to Day 39, but the range was narrower in older than in younger groups (Table 6, Fig. 1). We have found that when ovulation occurs in long cycles it comes late, but in cycles of moderate length there is little or no correlation between cycle length and ovulation date. Ovulation occurred between Day lo and Day 18 in a majority of the cycles at all ages, but the proportion of cycles falling within this range was larger at 2~9 years (79-86 per cent) than at years (62-68 per cent) or at years (71.4 per cent). Late ovulation (Day 18 or later) became less frequent with increasing age up to 40 years, and thereafter became

6 442 COLLETT ET Al. Fertility & Sterility more frequent as the cycles lengthened. Very early ovulation (before the Day 10) was observed at all ages, but occurred less often at years than in the older or younger groups. The mean day of ovulation was slightly earlier at years than at years, and at years was earlier still. However at years the mean again rose. TABLE 6. Time of Ovulation Day of ovulation Age (Yr. ) Range Mode Mean All ages Duration of Luteal Phase We observed a range of 4-26 days in the duration of the luteal phase (Table 7, Figs. 1 and 2). It lasted days in per cent of the cycles TABLE 7. Duration of Luteal Phase Duration in days Age Range Mode Mean (Yr.) No. Cycles (da.) (da. ) (da. ) All ages between 20 and 50 years, and in a somewhat smaller proportion (67.9 per cent) of the cycles at years. If a shorter range is considered (12-16 days) a similar age difference is observed, although the number falling within this range was smaller than expected, per cent as compared with 88 per cent reported by Rock and Hertig. The mean duration of the luteal phase was days at ages 17-34, but at and the

7 REGULARS VARIABILITY OF PHASES OF THE OVARIAN CYCLE ' MIRREGUl.A n ~Follic:ular Phase ~ Luteal Phase Fig. 2. Variability of phases of ovarian cycles among "regulars" or "irregulars."

8 444 COllETT ET AL. Fertility & Sterility mean was slightly less (11 and 12.9 days). Examination of the variation found in individual records as well as the range found in the various age groups suggests that the current opinion that the luteal phase lasts about 14 days may be the result of statistical treatment of data rather than of actual examination of individual curves. 2 Luteal phases of less than 10 days were found by Goldzieher et ai. in 1.8 per cent of the cycles observed, most of which fell between 25 and 34 years. We found such short phases in 4.5 per cent of the cycles at these ages. The proportion of short luteal phases was higher in our older and younger groups that at intermediate ages. Long luteal phases (18 days or over) were least frequent at years. TABLE 8. Magnitude of Rise in degrees Fahrenheit Age First day (Yr.) Cycles _ Mode Mean All ages Luteal Temperature Rise The initial postovulatory temperature rise in our series was clearly sharper in the younger than in the older groups: a rise of F. or more was found in per cent of the years group and in only per cent of the year (Table 8, Fig. 1). A similar age difference is found if a.rise of F. or more is considered per cent for the year olds, and per cent for the year olds. The sustained postovulatory temperature rise in our series was 0.8 F. or more in per cent of all 0 diphasic cycles of subjects years old, and in 90 per cent of those between 40 and 50. The proportion of cycles showing a sustained rise of F. or more was of course smaller, but it increased from 80 per cent at to 90 per cent at and then diminished to 70 per cent at years. Jones, in checking the temperature rise against biopsy and preg-

9 Vol. 5, No.5, 1954 MENSTRUAL CYCLE AND AGE 445 nanediol excretion as a quantitative measure of luteal adequacy, found that "a temperature rise of less than is evidence of an inadequate luteal phase." On this basis, 3.5 per cent of our series of diphasic cycles showed luteal inadequacy. Deficiency was most frequently noted in the oldest and youngest groups, and least frequently between 30 and 39 years. Cycle to Cycle Variation Successive cycles in the same individual often showed marked variability in all respects (Fig. 2). Regularity of cycle length in both long and short cycles was often not accompanied by regularity in date of ovulation or length of the luteal phase. Using as a criterion of regularity a difference ol Postovulatory Temperature Rise Rise in degrees Fahrenheit Age Maximum rise (Yr.) Cycles _ Mode Mean All ages days or less in cycle length, we show in Fig. 2 a group of regularly cyclic women in whom the shift in ovulation date and in length of the luteal phase was sometimes considerable. For instance, Subject 123 during 6 cycles showed a variation in ovulation date from Day 5 to Day 18, and in the luteal phase a variation of days. In Subject 50 an early and a late ovulation occurred together with an anovulatory cycle. A second group, of irregularly cyclic women in whom the difference in cycle length was more than 5 days, showed a variation in cycle length of days (Subject 127) and of days (Subject 401). These same subjects also showed wide fluctuation in ovulation date: Day 4 to Day 53 for Subject 127 and Day 4 to Day 24 for Subject 401. It is evident from the graphs (Fig. 2 and privately printed graphs) that the luteal phase is by no means constant in a given individual even though it varies less than the follicular phase.

10 446 COLLETT ET At. Fertility & Sterility Types of Basal Temperature Curve The normal basal temperature curve is usually described as diphasic, the first portion (corresponding to the follicular phase) being low and followed by a well-defined temperature shift to a higher level (the luteal phase).26 The anovulatory curve is monophasic, the fluctuations showing no regular pattern. We have observed considerable variation in the form of the diphasic curve at all ages, but particularly in the youngest and oldest groups. Sometimes the follicular phase is a straight line and sometimes it fluctuates, though always with a downward trend. In the luteal phase the curve sometimes rises sharply and reaches its maximum within 1 or 2 days, but often although the same maximum is attained the rise is gradual and covers a longer period. The low point before the rise is usually unmistakable, but sometimes a curve will show two low points fairly close together. We have also seen clearly diphasic curves in which the luteal rise is low. Many of these variations have been described by Cameron. SUMMARY 1. This paper reports basal temperature or basal metabolism curves for 302 complete cycles of 146 women between 17 and 50 years of age. 2. Length of cycle is less constant in the and year groups than at other ages. 3. The most frequent menstrual length is 5 days at all ages, although a range of 2-9 days was observed. After 35 fewer long menses occur. 4. The incidence of anovulatory cycles is highest at years and fairly high at 40-50, but such cycles occur sporadically at other ages. They occur least often at years. 5. Ovulation may occur at any time from Day 4 to Day 39 of the cycle, but between the ages of 25 and 34 it falls most frequently between Day 12 and Day 15. Variability is greatest before 20 and after 40 years. 6. The luteal phase, which generally lasts days, varies at all ages although less than the follicular phase. Short luteal phases are more often observed before 25 and after 40 than at other ages, and long luteal phases most often before 20 years. 7. A rise of F. or more in the luteal phase occurred in per cent of the diphasic cycles of the youngest and oldest groups as compared with per cent of the cycles of women years old. Similar but more

11 Vol. 5, No.5, 1954 MENSTRUAL CYCLE AND AGE 447 striking age differences were observed in luteal phases showing a rise of 1.0 F. or more. The initial rise was sharpest in the younger groups. 8. In all respects the stability and efficiency of ovarian activity was greatest at years, less at and years, and least at and years. 9. Monophasic anovulatory curves are usually distinguishable from diphasic curves; there are however several types of diphasic curve, some of which are puzzling. REFERENCES 1. ABARBANEL, A. R. Pregnancy Tests. Hollywood Reporting Service, Hollywood, California (A. Study Internal Secretions), 1945, p BARTELMEZ, G. W. Factors in the variability of the menstrual cycle.. Anat. Rec. 115:101, BARTON, M., and WIESNER, B. P. Waking temperature in relation to female fecundity. Lancet 2:663, BERGMAN, P. The sexual cycle: Time of ovulation and time of optimum fertility in women. Acta obst. et gynec. scandinav. 29:1, Supp1.4, BERGMAj'<, P. Studies on basal body temperature, endometrium, and cervical mucus. Acta obst. et gynec. scandinav. 30:292, Suppl. 7, BREWER, J. 1., and Jones, N. O. Time of ovulation. Am. J. Obst. & Gynec. 53: 137, BUXTON, C. L., and ENGLE, E. T. Time of ovulation: Correlation between basal temperature, appearance of endometrium and appearance of ovary. Am. /. Obst. & Gynec. 60:539, B. CAMERON, A. T. Recent Advances in Endocrinology (ed. 6). Philadelphia, Blakiston, 1947, p. 2BO. 9. COLLETT, M. E. Basal metabolism at the menopause. /. Appl. Physiol. 1 :629, CORNER, G. W. The Hormones in Human Reproduction. Princeton, Princeton Univ., 1942, p. 15B. 11. D'AMOUR, F. E. Comparative methods used in determining the time of ovulation. /. Glin. Endocrinol. 3:41, DAVIS, M. E. Clinical view of waking temperature. /.A.M.A. 130:929, DECKER, A. Culdoscopic observations on the tubo-ovarian mechanisms of ovum reception. Fertil. & Steril. 2:253, DIDDLE, D. W. Relation of intermenstrual symptoms to ovulation as determined by basal body temperature. Am. J. Obst. & Gynec. 56:527, DORING, G. K. Ein Beitrag zur Frage der Periodischen Fruchtbarkeit der Frau auf Grund von Erfahrungen bei der Zyklusanalyse mit Hilfe der Temperaturmessung. Geburtsh. u. Frauenh. 10:515, DOYLE, J. B. Exploratory culdotomy for observation of tubo-ovarian physiology at ovulation time. Fertil. & Steril. 2:475, FARRIS, E. J. Human Fertility. White Plains, New York, Authors Press, lb. FRANKEN, H. D. Menstruationszyklus und Ovulation. Deutsche med. Wchnschr. 76:229, GoLDZIEHER, J. W., HENKIN, A. E., and HAMBLIN, E. C. Characteristics of normal menstrual cycle. Am. J. Obst. & Gynec. 54:66B, 1945.

12 448 COLLETT ET At. Fertility & Sterility 20. GREULICH, W. W. Reliability of "basal" temperature changes as an index of ovulation in women. Trans. Am. Soc. Study Sterility, 1946, p HALBRECHT, 1. Artificial insemination. Lancet 2:668, HARTMAN, C. G. Time of Ovulation in Women. Baltimore, Williams & Wilkins, HARTMAN, C. G. Studies on reproduction in monkey and man. Endocrinology 25:670, HILLEBRAND, H. Die Bedeutung der Morgentemperaturkurven zur Bestimmung des Ovulationstermins fur den Fachgynakologen und ftir den Praktischen Arzt. 25. Munchen. med. Wchnschr. 93:735,1951. HORSKY, J., and MARSALEK, J. Die Basaltemperatur bei Physiologischen und Pathologischen Zustanden der Frau. Gynaecologia 129:396, ISRAEL, S. L., and SCHNELLER, O. Thermogenic property of progesterone. Fertil. & Steril. 1: 53, JACKSON, M. H. Clinical methods of dating ovulation. Practitioner 169: 151, JONES, G: E. S. Some newer medical aspects of the management of infertility. /.A.M.A. 141: 1123, LARSON, E. M. The menstrual cycle length and variability of young adult women. Am. J. Obst. & Gynec. 54:1069, MARTIN, P. L. Basal temperature and endometrial biopsy. Am. /. Obst. & Gynec. 46:53, PALMER, A. Basal temperature: Correlation with time. Am. /. Obst. & Gynec. 59:155,1950. PAYNE, S. Infertility in the female. A. Study Internal Secretions, 1948, p POMMERENKE, W. T., and VIERGIVER, E. Relationship between cervical mucus and basal temperature cycles. Am. /. Obst. & Gynec. 51: 192, ROBSON, J. M. Recent Advances in Sex and Reproductive Physiology (ed. 3). Philadelphia, Blakiston, 1947, Chapter IX. 35. ROCK, J., and HERTIG, A. J. Some aspects of early human development. Am. /. Obst. & Gynec. 44:973, ROGERS, J., and STURGIS, S. H. Pregnandiol excretion in normal women. /. Glin. Endocrinol. 10:89, ROTH, O. A., and BURGER, H. Dber die Bedeutung der Vaginalsmearmethode nach Papanicolaou zur Bestimmung des Ovulationstermins im Vergleich zur Pregnandiolausscheidung und Morgentemperaturkurve. Zentralbl. Gyniik. 73:931, RUBENSTEIN, B. B. The vaginal smear-basal temperature technique and its application to the study of functional sterility in woman. Endocrinology 27:843, SIEGLER, S. L., and SIEGLER, A. M. Evaluation of the basal body temperature. Fertil. & Steril. 2:287, TOMPKINS, P. Basal body temperature graphs as an index to ovulation. /. Obst. & Gynaec. Brit. Emp. 52:241, TOMPKINS, P. Timing of ovulation by basal temperature graphs. M. Glin. North America 29:1425, TOPKINS, P. Endometrial biopsy determination of incidence of ovulation in 402 regularly menstruating women. Ferti!. & Steril. 4:76, VOLLMAN, U. Untersuchungen tiber die Korpertemperatur der Frau in Korrelation zu den Phasen ihres Genitalzyklus. Monatschr. f. Geburtsh. u. Gyniik. 111:411, WONG, A. S. H., ENGLE, E. T., and BUXTON, C. L. Anovulatory menstruation in women. Am. J. Obst. & Gynec. 60:790,1950.

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