Normal variation in the length of the luteal phase of the menstrual cycle: identification of the short luteal phase

Transcription

1 Brtsh Journal of Obstetrcs and Gvnaecologjl July 1984, Vol. 9 1, pp Normal varaton n the length of the luteal phase of the menstrual cycle: dentfcaton of the short luteal phase ELIZABETH A. LENTON, BRITT-MARIE LANDGREN* & LYNNE SEXTON Unversty Department of Obstetrcs and Gynaecology, Jessop Hosptal for Women, Shefeld and "Karolnska Insttute, Stockholm, Sweden Summary. Normal probablty plots were used to assess the homogenety of a populaton of 327 luteal phases from apparently ovulatory menstrual cycles. The length of the luteal phase was defned as the nterval (n days) followng but not ncludng, the lutenzng hormone peak, up to and ncludng the day before onset of menstruaton. A small sub-set of the populaton conssted of cycles wth abnormally short luteal phases but the majorty of the data followed a normal frequency dstrbuton whch gave a mean (+ SD) for normal luteal phase length of (k 1.41) days. It was estmated that all cycles wth a luteal phase < 9 days were abnormal, and that 74%, 22% and 2% respectvely of cycles wth luteal phases of 1, 11 and 12 days were also abnormal. The total ncdence of short luteal phases defned as above was 5.2%. The medan lengths of the luteal phase obtaned usng methods such as the thermal shft (on basal body temperature records), ntermenstrual pan or cervcal mucorrhoea (Vollman 1977) are quoted as 11.8, 14.3 and 16. days respectvely. However, others (Strott et al. 197; Sherman & Korenman 1974; Abraham et al. 1972) have descrbed Meal phases whch last less than 12 or 13 days as abnormally short. Clearly there s a need for a precse estmaton of the duraton of a normal luteal phase based on a clear objectve parameter such as the lutenzng hormone (LH) peak. Assessment of the varablty of luteal phase length wthn the normal populaton wll allow us to dentfy more objectvely those cycles wth abnormally short luteal phases. Ths s mportant because such cycles may have dmnshed fertlty potental and must be dentfed as part of the routne nvestgaton of the nfertle couple. Correspondence: Elzabeth A. Lenton, Unversty Department of Obstetrcs and Gynaecology, Jessop Hosptal for Women, Leavygreave Road, Sheffeld S3 7RE The present study descrbes the varaton n luteal phase length n a large seres of apparently ovulatory women, and attempts to defne the upper and lower lmts of normal luteal phase length. Subjects and methods Daly blood samples were collected durng 335 cycles for the estmaton of the md-cycle lutenzng hormone (LH) peak (Lenton et al. 1978; Landgren et al. 198). Eght of these cycles were subsequently excluded from analyss ether because there was no LH peak (fve cycles) or they lasted >4 days (three cycles). The women n ths study have been descrbed prevously (Lenton et al. 1984). They were ntally dvded nto four groups as follows: group I, Swedsh women aged years; group 11, Brtsh women aged years; group 111, Brtsh women aged 22 to 39 years from an nfertlty clnc and group IV, Brtsh women aged between 4-5 years. All of the subjects from the nfertlty clnc had regular apparently ovulatory cycles; some had 685

2 686 E. A. Lenton et al. x ;p z $ 15 m?? U 1 5 a b I / / ',OR' _ 4- n 5; 4 3 ~ I I I I I I I Length of luteal phase (days) 2 Fg. 1. The frequency dstrbuton (a) and tne normal probablty plot (probt) (b) of luteal phase length from 327 apparently ovulatory menstrual cycles. tuba1 or male problems whch were consdered the cause of ther nfertlty but n others no explanaton for ther nfertlty could be ascertaned. DeJnton By conventon, the frst day of menstrual bleedng was defned as day 1 and the last day of the menstrual cycle was taken as the day before the start of the next menstrual perod. The luteal phase was defned as the number of days followng but not ncludng the day of maxmum LH concentratons, up untl the last day of the cycle. Statstcal analyss The frequency dstrbuton of length of luteal phase was studed wth the ad of the normal probablty plot (Wlk & Gnanadeskon 1968). The data are placed n ncreasng rank order and then plotted aganst the correspondng values from a standard normal (Gaussan) dstrbuton. A straght lne ndcates normalty. A deflecton n ether tal may ndcate that the data have been sampled from a mxture of two normal populatons wth possbly dfferent means and standard devatons. The method of maxmum lkelhood permts ths model to be ftted explctly (Johnson & Kotz 197), and provdes estmates of the two means and SDs and the proporton of each populaton that s present. A x2 statstc may be used to ndcate whether the two-normal model s a sgnfcantly better ft than one-normal. Statstcal dfferences between phase length dstrbutons were tested usng the Kruskall-Walls test (Sege1 1956) followed by Scheffe all-pars analyss to locate those groups whch dffered sgnfcantly. Results After dentfcaton of the LH peak, the length of the luteal phase was calculated for all 327 menstrual cycles. There were no sgnfcant dfferences between the subject groups, so the data were pooled and ther overall frequency dstrbuton calculated (Fg. la). Most of the luteal phases lay between 11 and 17 days, but the dstrbuton was slghtly skewed to the left by a small number of cycles wth shorter phases. The normal probablty plot (Fg. Ib) showed that most of the ponts fell on a straght lne, ndcatng a normal dstrbuton, but a deflecton n the curve occurred at about 11 days, suggestng that the two-normal model mght be approprate, as descrbed n the prevous secton. The putatve populatons were

3 ~~ normal (the majorty) and short luteal phase (mnorty). The model was ftted usng a computer program wrtten n Fortran and the resultng estmates are gven n Table I. There was no sgnfcant mprovement n the ft by allowng separate SDs for populatons I and 11, so a common value was calculated. The xz for ths restrcted two-normal model was 48. (2 d.f., P<. I), ndcatng a sgnfcantly better ft than one-normal. After excluson of the 5 2%) of luteal phase lengths whch appeared to be short, mean normal luteal phase duraton was found to be days wth 68% and 95%) confdence lmts of 12.7 to 15.5 and 11.3 to 17. days respectvely. By comparng the observed frequency dstrbuton (YO) wth that predcted by the twonormal model, t was possble to calculate the proporton of luteal phases of any duraton that were short (Table 2). These presumptvely abnormal cycles were all those for whch the luteal phase was < 9 days, but only 14%, 22% and 2% respectvely where the luteal phase was 1, 11 or 12 days. Vrtually all luteal phases of > 13 days Table 1. Estmates for the two-normal populaton model of luteal phase length Populaton I ( short ) Populaton I1 ( normal ) Mean (days) SD Proporton (%) Normal and abnormal lutealphase length 687 could be consdered normal, accordng to our analyss. Effects of subject group Although no sgnfcant dfferences between groups had been found ntally, t was felt that the group contanng women recruted from an nfertlty clnc mght tend to have a hgher ncdence of shorter luteal phases. However, there were no dfferences n the frequency of short luteal phase cycles between any of the groups (Table 3). Effect of age In order to assess whether duraton of the luteal phase changes wth age, the subjects were reallocated to sx groups accordng to ther age at the tme of samplng. Because of the nfluence of short luteal phase cycles, only the non-parametrc Kruskall-Walls test could be appled. Ths showed that hghly sgnfcant dfferences (P <.1) n luteal phase length exsted between the age groups. Applcaton of the Scheffe test revealed that despte only small changes n mean cycle length the ncdence of short luteal phases vared sgnfcantly wth age (Table 4) wth a hgher ncdence of shorter cycles (< 9, < 1 days) n the youngest women (aged years) and the oldest women (aged 45-5 years). Dscusson The mean duraton of the luteal phase obtaned from assessment of cervcal mucus n a large seres of women (WHO Task Force on Methods Table 2. Observed relatve frequency dstrbuton (%) of luteal phase length n 327 cycles, wth predcted frequences from two-normal model, broken down nto estmated frequences from populatons 1 ( short ) and 11 ( normal ) Observed Duraton of frequency Predcted frequency dstrbuton luteal phase dstrbuton Estmated YO (days) (%I Pop. I Pop. I1 Total populaton 1 I o o

4 688 E. A. Lenton et al. Table 3. The ncdence of luteal phases of < 9, < 1 and < 1 1 day@ respectvely n each of the subject groups The cumulatve percentage of cycles wth luteal phases of Subject group I Volunteers (Swedsh) 11 Volunteers (Brtsh) 111 lnfertlty patents (Brtsh) IV Older women (Brtsh) Overall < 9 days < 1days < 11 days alt s estmated that only 22% of cycles wth a luteal phase of 11 days wll actually be abnormally short (see text). Table 4. The ncdence of luteal phases of < 9, < 1 and < 1 la days n 325 menstrual cycles n women of dfferent ages Age range No of The cumulatve percentage of cycles wth luteal phases (years) cycles < 9 days < 1days < 11 days alt s estmated that only 22% of cycles wth a luteal phase of 11 days wll actually be abnormally short (see text). for the Determnaton of the Fertle Perod 1983) was 13.5 (SD 2.8) days and n the present study (usng the LH peak as a marker) the luteal phase was found to last days (SD 1.41 days). It s dffcult to compare these observatons snce the tme of the LH peak correlates wth the day of maxmum cervcal mucus n only 44% of subjects (Templeton et al. 1982). However, the relatonshp between the LH peak and ovulaton has been defned (WHO Task Force on Methods for the Determnaton of the Fertle Perod 198). Assumng that ovulaton occurs 16.5 h (.69 days) after the maxmum LH concentraton (WHO Task Force for the Determnaton of the Fertle Perod, 198), then ovulaton occurs.31 day before the luteal phase (as defned here) begns. By addng.31 to a value of days s obtaned whch agrees closely wth the geometrc mean luteal phase length (14.3 days) calculated usng the parameter ntermenstrual pan (Vollman 1977). Ths suggests that ntermenstrual pan may well be assocated wth actual event of ovulaton (Ham et al. 1979; Marnho et al. 1982). Abnormal (.e. outsde the normal dstrbuton) luteal phases were defned as all those lastng Q 9 days, 74% of phases lastng 1 days and 22% of phases lastng 11 days. For practcal purposes all luteal phases lastng between 12 and 17 days (nclusve) can be consdered normal. Agan ths fndng s n far agreement wth the rule-of-thumb approach adopted by both Abraham et al. (1 9 72) and Strott et al. (197) to dentfy short luteal phases. However, t should be noted that only some cycles wth luteal phases of I1 days are lkely to be abnormal, some wll be normal and eventually t may be possble to dstngush these types by scrutny of plasma progesterone profles (S. K. S. Smth & E. A. Lenton, unpublshed observatons). Surprsngly the ncdence of short luteal phases s constant at about 5-6% for all the populatons studed. Chronologcal age has only a small effect on the ncdence of short luteal phases, whch tend to occur more frequently at ether end of the reproductve age spectrum (Sherman & Korenman 1975). In ths study no luteal phase lastng > 18 days was recorded. In vew of the hgh frequency of

5 Normal and abnormal lutealphase length 689 subclncal pregnances (Edmonds et al. 1982) n normal women exposed to unprotected cotus, one would expect to see some cycles wth slghtly longer than normal luteal phases. Although none of the Swedsh or Brtsh volunteer groups were attemptng to become pregnant, all of the nfertle women were actvely tryng to conceve. Ths suggests that the ncdence of subclncal pregnances n women wth unexplaned nfertlty may n fact be very low. Acknowledgments The authors are ndebted to Mr J. P. Royston of the MRC Clncal Research Centre who generously provded consderable statstcal help and advce. References Abraham, G. E., Odell, W. D., Swedloff, R. S. & Hopper, K. (1972) Smultaneous radommunoassay of FSH, LH, progesterone, 17-hydroxyprogesterone and estradol- 17 durng the menstrual cycle. J Cln EndocrnolMetab 34, Edmonds, D. K., Lndsay, K. S., Mller, J. F., Wllamson, E. & Wood, P. J. (1982) Early embryonc mortalty n women. Fertl Sterl 38, Hann, L. E., Hall, D. A. & Black, E. B. (1979) Mttelschmerz. Sonograph demonstraton. JAMA 241, Johnson, N. L. & Kotz, S. (197) Contnuous Unvarate Dstrbutons-Z. John Wley, New York p. 92. Kletzy,. A., Nakamura, R. M., Thorneycroft, I. H. & Mshell, D. R. (1975) Lognormal dstrbuton of gonadotropns and ovaran sterod values n the normal menstrual cycle, Am J Obstet Gynecol 121, Landgren, B.-M., Unden, A.-L. & Dczfalusy, E. (198) Hormonal profles n the cycle of 68 normally menstruatng women. Acta Endocrnol 94, Lenton, E. A., Adams, M. & Cooke, I. D. (1978) Plasma sterod and gonadotrophn profles n ovulatory but nfertle women. Cln Endocrnol 8, Lenton, E. A., Brook, L. M., Sobowale,. & Cooke, I. D. (1979) Prolactn concentratons n normal menstrual cycles and concepton cycles. Cln Endocrnol1, Lenton, E. A., Landgren, B.-M., Sexton, L. & Harper, R. (1984) Normal varaton n the length ofthe follcular phase of the menstrual cycle: effect of chronologcal age Br J Obstet Gynaecol91, Marnho, A. O., Sallam, H. N., Goessens, L., Collns, W. P. & Campbell, S. (1982) Ovulaton sde and occurrence of Mttelschmerz n spontaneous and nduced ovaran cycles. Br Med J 284,632. Segel, S. (1956) Non-parametc Statstcs for the Behavoural Scences. McGraw-Hll, New York. Sherman, B. M. & Korenman, S. G. (1974) Measurement of plasma LH, FSH, estradol and progesterone n dsorders of the human menstrual cycle: the short luteal phase. J Cln Endocrnol Metab 38, Sherman, B. M. & Korenman, S. G. (1975) Hormonal characterstcs of the human menstrual cycle throughout reproductve lfe. J Cln Invest 55, Strott, C. A., Cargll, C. M., Ross, G. T. & Lpsett, M. B. (197) The short luteal phase. J Cln Endocrnol Metab 3, Templeton, A. A,, Penney, G. C. & Lees, M. M. (1982) Relaton between the lutenzng hormone peak, the nadr of the basal body temperature and the cervcal mucus score. Br J Obstet Gynaecol 89, Vollman, R. F. (1977) The menstrual cycle. Volume 7 n the seres Major Problems n Obstetrcs and Gynaecology. W. B. Saunders Co., Eastbourne. Wlk, M. B. & Gnanadeskon, R. (1968) Probablty plottng methods for the analyss of data. Bometrka 55, WHO Task Force on Methods for the determnaton of the Fertle Perod (198) Temporal relatonshps between ovulaton and defned changes n concentraton of plasma estradol- 17, lutensng hormone, follcle-stmulatng hormone and progesterone. Am J Obstet Gynecol, 138, WHO Task Force on Methods for the Determnaton of the Fertle Perod (1983) A prospectve multcentre study of the ovulaton method of natural famly plannng Characterstcs of the menstrual cycle and of the fertle phase. Fertl Sterl 4, Receved 6 May I983 Accepted 25 November I983