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Lower esophageal sphincter pressure during the normal menstrual cycle
Lower esophageal sphincter pressure during the normal menstrual cycle DAVID
H.
,JUDITH JOHN
VAN
THIEL.
M.D.”
S. GAVALER,
B.A.
F. STREMPLE,
Pitfshwgh,
M.D.
Prnngli~nicc
Lower esophageal sphincter pressure (LESP), basal gastric pH, and plasma levels of gastrin, estradiol, and progesterone were determined in ten women known to have normal menstrual cycles. All determinations were performed both during the follicular phase (Days 2 to 8) and during the luteal phase (Days 20 to 30). In addition, an intraluminal pH probe placed 5 cm. above the lower esophageal sphincter was used to test for the presence of acid reflux in response to three provocative procedures. LESP during the follicular phase was 19.0 2 1.5 mm. Hg (mean r SE&l.) and during the luteal phase 16.5 + 1.3 mm. Hg (p <: 0.01). Basal gastric pH and plasma gastrin levels were similar at both times. Plasma estradiol in the follicular phase (76.1 -e 7.0 pg. per milliliter) increased twofold during the luteal phase (159.0 i- 6.0) (p < 0.01). Plasma progasferone increased from a level of 1.5 t 0.8 ng. per milliliter during the follicular phase to 19.2 t 4.2 during the luteal phase. Coincident with these changes in LESP and increases in steroid levels, acid reflux was detected in five women during the luteal phase but was present in only one during the follicular phase. (AM. J. OBSTET. GYNECOL. 134:64, 1979.)
PREc;NANT woMEN experience a variety ofupper gastrointestinal complaints. These include heartburn, nausea, and early satiety which are commonly ascribed to the syndrome of’ “morning sickness.” Despite their frequency the pathophysiologic basis for the increased incidence of these complaints during pregnancy is poorly understood. Although the regulating role of estrogens and progesterone in regard to the contractile and bioelectricai activities ofniyometrium’~ 2 have been studied in detail, remarkably little has been studied relative to the effect of these sex steroids on gastrointestinal muscle. F‘rom the Dwkior~ CI/ Gu&oe~~terology, Department 01 Medicme, hivcnit~ of Pittsburgh School II/ Medicine. Supported AD0895-l.
in part by Nationnl
Receizledfor
publicatwn
RevLyed June
April
Institutes
of Health
Gram
27, 1978.
19, 1978.
~4ccepted June 20, 1978. Reprint requests: Dr. David H. Van Thiel, M.D., IOOOG Scaife Hall, Department of Medicine, Dizlision of Gastroenterology, lJnivers$ qf Pittsburgh School of Medicinr, Pittsburgh, Pennsylvania 15261. *Recipient Development
64
of United Award
States Public AA0001 6.
Health
&r&e
Career
Relative to this question, recent in vitro studies have shown progesterone, hut not estrogens, to reduce the tension which can be achieved in smooth muscle strips from the lower esophageal sphincter of the opossum in response to electrical, neurotransmitter and gastrointestinal hormonal stimuli.’ ’ ’ Moreover, recent studies in viva have suggested a role for either progesterone alone or the l.ombination of a potent estrogen followed by progesterone given sequentially as being responsible for a reduction in lower esophageal sphincter p&ssure (LESP) in pseudopregnant women and animals.‘, ’ As a direct extension of these earlier studies, we have asked the question, might not the same sequential changes in plasma levels of steroids which occur during the normal menstrual cycle, albeit to a much lesser drgree than during pregnancy, reduce LESP of women during the luteal phase as compared to the follicular phase of the menstrual cycle. The purpose of the present study was therefore to: (1) compare LESP in normal menstruating women during the follicular phase (Days 2 to 8) and during the iuteal phase (Days 20 to 30) of the menstrual cycle, and (2) determine whether changes in plasma sex steroid levels occurring as a result of o+ulation might correlate with measured changes in LESP. 0002-9378/79/090064+04$00.40/0
0 1979 The C. V.
Mosby Co.
Volume Number
134 1
Lower
esophageal
sphincter
Methods Volunteers; studied. Ten young adult normally menstruating women with a mean age of 24.6 ? 1.8 (S.E.M.) year,s (range 20 to 37) and known not to have been using oral contraceptives within a period of at least three months prior to their participation in this study were evaluated. Nine of the ten volunteers studied denied any prior history of symptomatic heartburn or other gastrointestinal disease. Before each study. informed consent was obtained from each volunteer. Moreover, be;fore the study was initiated, approval was obtained from the Human Research Review Committee of the University of Pittsburgh School of Medicine. Pittsburgh, Pennsylvania. Intraluminal pressure measurement. All studies were performed in the Gastrointestinal Laboratory of the Presbyterian-University Hospital of the University of Pittsburgh lichool of Medicine, Pittsburgh, Pennsylvania. All volunteers were studied in a supine position. Three water-filled polyvinyl tubes, 1.4 mm. in internal diameter, were combined with pH electrode as a single manometric tube. The tube was inserted into the stomach and slowly withdrawn at 1 cm. intervals with initial identification of the LES as an area of localized high pressure which relaxes with swallowing. The side openings of the pressure-transmitting catheters measured 1.3 mm. in diameter and were placed at 5 cm. intervals. intraluminal pressure was measured as pressure transmitted via these water-filled catheters to external pressure transducers (Statham 18429P 23AC) and recorded on a multichannel polygraph recorder (Grass 29349B). Each catheter was infused with distilled water at a constant rate of 0.5 ml. per minute. Sphincter pressure utilized fi)r analysis was recorded in millimeters of mercury at the end of inspiration using the rapid pull through technique (0.5 cm. per second) with intragastric pressure used as zero reference. The mean of three individual measurements of LESP made during a single pull through, and repeated for a total of three separate complete pull throughs, was used for statistical comparisons. At the perfusion flow rate used, the performance characteristics of the manometry equipment used in our laboratory detect changes in esophageal pressure at a rate of 70 mm. Hg per second. Procedures. All studies were performed in the morning after an overnight fast. Each volunteer was studied twice, once in the follicular phase (Days 2 to 8) and once in the luteal phase (Days 20 to 30) of one ot two consecutive menstrual cycles. Day 1 was defined as the first day of menstrual bleeding. Six volunteers were first studied in the follicular phase and subsequently studied in the luteal phase, while four volunteers were
pressure
during
normal
menstrual
cycle
65
LOWER ESOPHAGEAL SPHINCTER PRESSURE DURING THE NORMAL MENSTRUAL CYCLE
35
I
FOLLICULAR
PHASE OF MENSTRUAL
LUTEAL
CYCLE
Fig. 1. Lower esophageal sphincter pressure during the f’ollicular and luteal phases of the female volunteers studied. The solid lines connect the pressures for an individual The shaded area is the range of values for normal our laboratory without attention to the menstrual
volunteer. women in cycle.
studied in the luteal phase and subsequently studied in the follicular phase with the order being determined by the convenience of the volunteer. The investigator was blinded as to the sequence of the studies for a given volunteer until completion of both studies. Before each study, 20 C.C. of blood was drawn for determination of plasma levels of gastrin, estradiol, and progesterone. Basal gastric pH was recorded at the start of each motility study. The presence of reflux was evaluated in each volunteer at the end of each study. Reflux was considered present when following the instillation of 100 C.C. of 0. IN HCl into the stomach, acid (pH c4.0) was detected by an intraluminal pH probe positioned 5 cm. above the LES with the subject in the supine position during any of the following three provocative procedures: (1) sniffing against a closed nose and mouth, (2) prolonged Valsalva maneuver, andior (3) prolonged straight leg raising. Plasma gastrin. Blood for plasma gastrin was ohtained from each fasting volunteer before each study. Plasma was immediately separated and stored frozen at -20” C. until assayed. All gastrin determinations were performed in duplicate in a single assay by a radioimmunoassay method.” The sensitivity of the gastrin assay was 10 pg. per milliliter with an intra-assay variation of’ less than ten per cent.
first
66 Van Thiel, Gavaler, and Stremple
Table I. Plasma gastrin, estradiol, and progesterone levels in the volunteers studied during the two phases of the menstrual cycle Follicdar
Gastrin (pg./ml.) kktradiol (pg./ml.) Progesterone (ng./ml.)
phase
76 Ifr 3.0 76.1 f 7.0* 1.5 f 0.8*
Luteal phmp 81 +- 4.0 159.0 % 6.0 19.2 -c 4.2
*p < 0.01 Plasma steroids. Fasting blood for plasma cstradiol and progesterone was obtained t’rom each fasting wlttllteer bet&e each study. Plasma wn immediatel\ separated and stored frozen ar - 20” (1. until assayed using r~ldioinlniunoassa) methods.“. I” All samples ww run ill duplicate in a single as+ thus avoiding an! interassq variation. Inn-a-assa! variation of tht r;ldioiInmunoassa~ for each steroid teas less than ten per cent. The detection limit ot the cstradiol assa!’ \\.;I\ 1.O pg. and the detection limit of’ the progesterotw xxt) \vas IO pg. Interpretation of data. All manometric tracings and seutn samples were coded and r-ead or analyzed hlindl~ itfter all the studies were completed. The Student t tc’sl tot paired data \+as used for statistical analysis.
Comment
Results .I’he sphincter pressures recorded during the follicnlar and luteal phases of the menstrual cycle fi)r eat 11 patient are shown in Fig. 1. The mean pressure t S.E.M. during the follicular phase was 19.0 t 1.3 mm. Hg with a range from 12.0 to 30.0 mm. Hg. The nwan pressure during the luteal phase was Iti.3 2 I.3 mm. Hg with a range from 10.0 to 26.0 mm. Hg. The difIGrencc in I,ESP recorded between the follicular and luteal phase of these ten volunteers was significanrh different at the p < 0.01 level. All pressures but one were \vithin the range of values for normal women without regard to menstrual c!;cle changes in our Iahoratory. ‘The only pressure recorded outside the normal range for LES pressure was obtained during ~lre luteal phase of the individual volunteer’s menstrual cycle. Unprovoked symptomatic and pH probe positi\ t t-eflux was present in only one volunteer studied duling rhe folhcular phase (the only volunteer who had an LISP below the normal range). ‘The other nine volunleers failed to demonstrate reflux under either basal cx>nditions or in response to the three prwwativc~ stimuli utilized. During the luteal phase symp~otnati~ refius was present in the same volunteer cvho hat1 s)mpfoms during rhe follicular phase but was also pH I)robe positive in four additional wlunteers in responw
‘l‘he otbvr\csd deciittrh iti l.ESl’ ot these 1101ttial \()Iunteers tlurin~q rhe luteal phase ccmtpared to I,LSP during the tollicular phase, however. was small. I‘htls. onl\ one 01 the subjecta studied had ;it1 I.lCSP twottlctl olltside and bel(nv the range foi tiol-nial. It i, not ~iirprisirig, therefore. thar thy trtywnc!~ of sytnptorna~ic heartburn hat not been wportrd previousl\- to be increased in women during the luteal phase wntp;tretI to the folliculat phase of the tiicnstriia1 c cclc. \Yben provocative tests were utilized to evaluate for I he prw ence of qress-induced reflux, however. live of the ten Ivomen \vc studied hat1 1’I-I protje-positi\-e wlius (onI\ one was 51tnpUmiatic) during Ihe luteal phase conpared to only one during the loilic~ttlar I&w. It is no1 iinreasotiahlr to asstttne, tht-reii,r-cx. that the small t)ttt statistically significant redlwtion in I XSP obsvrvcd dur-illg the Irltral phase ot’ the twrlst rual c-vc.1~i11 ,1wrr1p-
Volume Number
134 1
Lower esophageal sphincter pressure during normal menstrual cycle 67
tomatic women is only clinically important when it occurs in conjunction with one or more other factors that also reduce LESP or stress the competence of the LES. The combined effect of several such factors acting together presumably might reduce LESP enough to produce symptomatic heartburn in the luteal phase more frequently than in the follicular phase of susceptible women. Consistent with such a formulation is our unpublished obslzrvation that female medical students experience symptomatic heartburn more commonly during the latter half of their menstrual cycles (Days 15 to 28, i.e., lutcal phase) than during the immediate postmenstrual period (follicular phase). Specifically, during the prcceeding three years 25 female medical students at the University of Pittsburgh who were not using oral contraceptives agreed to keep a diary of their menstrual cycles and when they experienced symptomatic heartburn. As a result of such cooperation, we have been able to observe these women during a total of 405 complete menstrual cycles. Arbitrarily
dividing each menstrual cycle into follicular phase (Days 1 to 14) and luteal phase (Days 14 to first day of vaginal bleeding) and then assigning each of the 135 documented episodes of heartburn to one or the other two menstrual cycle phases, we found a significant preponderance of symptomatic heartburn episodes during the luteal phase (I/? = 88.8889; p < 0.001) as compared to the follicular phase. The failure to detect a significant difference in basal gastric pH and plasma gastrin levels during the course of this study as well as in previous studies”, 6 tends to negate a role for either of these two factors in the genesis of the observed LESP reduction. In summary, these studies demonstrate that: (1) Basal resting LESP during the luteal phase of the menstrual cycle is reduced in women relative to LESP measurements recorded in the follicular phase, and (2) changes in basal gastric pH and plasma gastrin levels cannot account for this observed decline in LESP during the luteal phase as compared to the follicular phase.
REFERENCES 1. Melton, C. F., Jr.: Electrical activity in the uterus of the rat, Endocrinology 58: 139, 1956. 2. Marshall, J. M.: Effects of estrogen and progesterone on single uterine muscle fiber in the rat, Am. J. Physiol. 197:
935, 1959. 3. Fisher, R. S., Roberts, G. S., Grabowski, C. J., and Cohen, S.: Heartburn of pregnancy: A hormonal disorder, Clin. Res. 23: 284A, 1976. 4. Fisher, R. S., Mayer, E., and Grabowski, C.: Effects oforal contraceptive agents on the lower esophageal sphincter (LES), Clin. Res. 25: 3lOA, 1977. 5. Van Thiel, D. H., Gavaler, J. S., Joshi, S. N., and Stremple, J. F.: Heartburn of pregnancy, Gastroenterology 72: 666, 1977. 6. Van Thiel, D. H.. Gavaler, J. S., and Stremple, J. F.:
Lower esophageal sphincter pressure in women using sequential oral contraceptives, Gastroenterology 71: 232, 1976. 7. Schulze, K., and Christensen, J.: The lower sphincter of the opossum esophagus in pseudopregnancy, Gastroenterology (in press). 8. Yalow, R. S., and Berson, S. A.: Radioimmunoassay of gastrin, Gastroenterology 58: 1, 1970. 9. Hotchkiss, J., Atkinson, L. E., and Knobil, E.: Time course of serum estrogen and LH concentrations during the menstrual cycle of the Rhesus monkey, Endocrinology 89: 117, 1971. 10. Abraham, C. E., Swerdloff, R., Tulchinsky, D., and Odell, W. D.: Radioimmunoassay of plasma progesterone, J, Clin. Endocrinol. Metab. 32: 619, 1977.
H.
,JUDITH JOHN
VAN
THIEL.
M.D.”
S. GAVALER,
B.A.
F. STREMPLE,
Pitfshwgh,
M.D.
Prnngli~nicc
Lower esophageal sphincter pressure (LESP), basal gastric pH, and plasma levels of gastrin, estradiol, and progesterone were determined in ten women known to have normal menstrual cycles. All determinations were performed both during the follicular phase (Days 2 to 8) and during the luteal phase (Days 20 to 30). In addition, an intraluminal pH probe placed 5 cm. above the lower esophageal sphincter was used to test for the presence of acid reflux in response to three provocative procedures. LESP during the follicular phase was 19.0 2 1.5 mm. Hg (mean r SE&l.) and during the luteal phase 16.5 + 1.3 mm. Hg (p <: 0.01). Basal gastric pH and plasma gastrin levels were similar at both times. Plasma estradiol in the follicular phase (76.1 -e 7.0 pg. per milliliter) increased twofold during the luteal phase (159.0 i- 6.0) (p < 0.01). Plasma progasferone increased from a level of 1.5 t 0.8 ng. per milliliter during the follicular phase to 19.2 t 4.2 during the luteal phase. Coincident with these changes in LESP and increases in steroid levels, acid reflux was detected in five women during the luteal phase but was present in only one during the follicular phase. (AM. J. OBSTET. GYNECOL. 134:64, 1979.)
PREc;NANT woMEN experience a variety ofupper gastrointestinal complaints. These include heartburn, nausea, and early satiety which are commonly ascribed to the syndrome of’ “morning sickness.” Despite their frequency the pathophysiologic basis for the increased incidence of these complaints during pregnancy is poorly understood. Although the regulating role of estrogens and progesterone in regard to the contractile and bioelectricai activities ofniyometrium’~ 2 have been studied in detail, remarkably little has been studied relative to the effect of these sex steroids on gastrointestinal muscle. F‘rom the Dwkior~ CI/ Gu&oe~~terology, Department 01 Medicme, hivcnit~ of Pittsburgh School II/ Medicine. Supported AD0895-l.
in part by Nationnl
Receizledfor
publicatwn
RevLyed June
April
Institutes
of Health
Gram
27, 1978.
19, 1978.
~4ccepted June 20, 1978. Reprint requests: Dr. David H. Van Thiel, M.D., IOOOG Scaife Hall, Department of Medicine, Dizlision of Gastroenterology, lJnivers$ qf Pittsburgh School of Medicinr, Pittsburgh, Pennsylvania 15261. *Recipient Development
64
of United Award
States Public AA0001 6.
Health
&r&e
Career
Relative to this question, recent in vitro studies have shown progesterone, hut not estrogens, to reduce the tension which can be achieved in smooth muscle strips from the lower esophageal sphincter of the opossum in response to electrical, neurotransmitter and gastrointestinal hormonal stimuli.’ ’ ’ Moreover, recent studies in viva have suggested a role for either progesterone alone or the l.ombination of a potent estrogen followed by progesterone given sequentially as being responsible for a reduction in lower esophageal sphincter p&ssure (LESP) in pseudopregnant women and animals.‘, ’ As a direct extension of these earlier studies, we have asked the question, might not the same sequential changes in plasma levels of steroids which occur during the normal menstrual cycle, albeit to a much lesser drgree than during pregnancy, reduce LESP of women during the luteal phase as compared to the follicular phase of the menstrual cycle. The purpose of the present study was therefore to: (1) compare LESP in normal menstruating women during the follicular phase (Days 2 to 8) and during the iuteal phase (Days 20 to 30) of the menstrual cycle, and (2) determine whether changes in plasma sex steroid levels occurring as a result of o+ulation might correlate with measured changes in LESP. 0002-9378/79/090064+04$00.40/0
0 1979 The C. V.
Mosby Co.
Volume Number
134 1
Lower
esophageal
sphincter
Methods Volunteers; studied. Ten young adult normally menstruating women with a mean age of 24.6 ? 1.8 (S.E.M.) year,s (range 20 to 37) and known not to have been using oral contraceptives within a period of at least three months prior to their participation in this study were evaluated. Nine of the ten volunteers studied denied any prior history of symptomatic heartburn or other gastrointestinal disease. Before each study. informed consent was obtained from each volunteer. Moreover, be;fore the study was initiated, approval was obtained from the Human Research Review Committee of the University of Pittsburgh School of Medicine. Pittsburgh, Pennsylvania. Intraluminal pressure measurement. All studies were performed in the Gastrointestinal Laboratory of the Presbyterian-University Hospital of the University of Pittsburgh lichool of Medicine, Pittsburgh, Pennsylvania. All volunteers were studied in a supine position. Three water-filled polyvinyl tubes, 1.4 mm. in internal diameter, were combined with pH electrode as a single manometric tube. The tube was inserted into the stomach and slowly withdrawn at 1 cm. intervals with initial identification of the LES as an area of localized high pressure which relaxes with swallowing. The side openings of the pressure-transmitting catheters measured 1.3 mm. in diameter and were placed at 5 cm. intervals. intraluminal pressure was measured as pressure transmitted via these water-filled catheters to external pressure transducers (Statham 18429P 23AC) and recorded on a multichannel polygraph recorder (Grass 29349B). Each catheter was infused with distilled water at a constant rate of 0.5 ml. per minute. Sphincter pressure utilized fi)r analysis was recorded in millimeters of mercury at the end of inspiration using the rapid pull through technique (0.5 cm. per second) with intragastric pressure used as zero reference. The mean of three individual measurements of LESP made during a single pull through, and repeated for a total of three separate complete pull throughs, was used for statistical comparisons. At the perfusion flow rate used, the performance characteristics of the manometry equipment used in our laboratory detect changes in esophageal pressure at a rate of 70 mm. Hg per second. Procedures. All studies were performed in the morning after an overnight fast. Each volunteer was studied twice, once in the follicular phase (Days 2 to 8) and once in the luteal phase (Days 20 to 30) of one ot two consecutive menstrual cycles. Day 1 was defined as the first day of menstrual bleeding. Six volunteers were first studied in the follicular phase and subsequently studied in the luteal phase, while four volunteers were
pressure
during
normal
menstrual
cycle
65
LOWER ESOPHAGEAL SPHINCTER PRESSURE DURING THE NORMAL MENSTRUAL CYCLE
35
I
FOLLICULAR
PHASE OF MENSTRUAL
LUTEAL
CYCLE
Fig. 1. Lower esophageal sphincter pressure during the f’ollicular and luteal phases of the female volunteers studied. The solid lines connect the pressures for an individual The shaded area is the range of values for normal our laboratory without attention to the menstrual
volunteer. women in cycle.
studied in the luteal phase and subsequently studied in the follicular phase with the order being determined by the convenience of the volunteer. The investigator was blinded as to the sequence of the studies for a given volunteer until completion of both studies. Before each study, 20 C.C. of blood was drawn for determination of plasma levels of gastrin, estradiol, and progesterone. Basal gastric pH was recorded at the start of each motility study. The presence of reflux was evaluated in each volunteer at the end of each study. Reflux was considered present when following the instillation of 100 C.C. of 0. IN HCl into the stomach, acid (pH c4.0) was detected by an intraluminal pH probe positioned 5 cm. above the LES with the subject in the supine position during any of the following three provocative procedures: (1) sniffing against a closed nose and mouth, (2) prolonged Valsalva maneuver, andior (3) prolonged straight leg raising. Plasma gastrin. Blood for plasma gastrin was ohtained from each fasting volunteer before each study. Plasma was immediately separated and stored frozen at -20” C. until assayed. All gastrin determinations were performed in duplicate in a single assay by a radioimmunoassay method.” The sensitivity of the gastrin assay was 10 pg. per milliliter with an intra-assay variation of’ less than ten per cent.
first
66 Van Thiel, Gavaler, and Stremple
Table I. Plasma gastrin, estradiol, and progesterone levels in the volunteers studied during the two phases of the menstrual cycle Follicdar
Gastrin (pg./ml.) kktradiol (pg./ml.) Progesterone (ng./ml.)
phase
76 Ifr 3.0 76.1 f 7.0* 1.5 f 0.8*
Luteal phmp 81 +- 4.0 159.0 % 6.0 19.2 -c 4.2
*p < 0.01 Plasma steroids. Fasting blood for plasma cstradiol and progesterone was obtained t’rom each fasting wlttllteer bet&e each study. Plasma wn immediatel\ separated and stored frozen ar - 20” (1. until assayed using r~ldioinlniunoassa) methods.“. I” All samples ww run ill duplicate in a single as+ thus avoiding an! interassq variation. Inn-a-assa! variation of tht r;ldioiInmunoassa~ for each steroid teas less than ten per cent. The detection limit ot the cstradiol assa!’ \\.;I\ 1.O pg. and the detection limit of’ the progesterotw xxt) \vas IO pg. Interpretation of data. All manometric tracings and seutn samples were coded and r-ead or analyzed hlindl~ itfter all the studies were completed. The Student t tc’sl tot paired data \+as used for statistical analysis.
Comment
Results .I’he sphincter pressures recorded during the follicnlar and luteal phases of the menstrual cycle fi)r eat 11 patient are shown in Fig. 1. The mean pressure t S.E.M. during the follicular phase was 19.0 t 1.3 mm. Hg with a range from 12.0 to 30.0 mm. Hg. The nwan pressure during the luteal phase was Iti.3 2 I.3 mm. Hg with a range from 10.0 to 26.0 mm. Hg. The difIGrencc in I,ESP recorded between the follicular and luteal phase of these ten volunteers was significanrh different at the p < 0.01 level. All pressures but one were \vithin the range of values for normal women without regard to menstrual c!;cle changes in our Iahoratory. ‘The only pressure recorded outside the normal range for LES pressure was obtained during ~lre luteal phase of the individual volunteer’s menstrual cycle. Unprovoked symptomatic and pH probe positi\ t t-eflux was present in only one volunteer studied duling rhe folhcular phase (the only volunteer who had an LISP below the normal range). ‘The other nine volunleers failed to demonstrate reflux under either basal cx>nditions or in response to the three prwwativc~ stimuli utilized. During the luteal phase symp~otnati~ refius was present in the same volunteer cvho hat1 s)mpfoms during rhe follicular phase but was also pH I)robe positive in four additional wlunteers in responw
‘l‘he otbvr\csd deciittrh iti l.ESl’ ot these 1101ttial \()Iunteers tlurin~q rhe luteal phase ccmtpared to I,LSP during the tollicular phase, however. was small. I‘htls. onl\ one 01 the subjecta studied had ;it1 I.lCSP twottlctl olltside and bel(nv the range foi tiol-nial. It i, not ~iirprisirig, therefore. thar thy trtywnc!~ of sytnptorna~ic heartburn hat not been wportrd previousl\- to be increased in women during the luteal phase wntp;tretI to the folliculat phase of the tiicnstriia1 c cclc. \Yben provocative tests were utilized to evaluate for I he prw ence of qress-induced reflux, however. live of the ten Ivomen \vc studied hat1 1’I-I protje-positi\-e wlius (onI\ one was 51tnpUmiatic) during Ihe luteal phase conpared to only one during the loilic~ttlar I&w. It is no1 iinreasotiahlr to asstttne, tht-reii,r-cx. that the small t)ttt statistically significant redlwtion in I XSP obsvrvcd dur-illg the Irltral phase ot’ the twrlst rual c-vc.1~i11 ,1wrr1p-
Volume Number
134 1
Lower esophageal sphincter pressure during normal menstrual cycle 67
tomatic women is only clinically important when it occurs in conjunction with one or more other factors that also reduce LESP or stress the competence of the LES. The combined effect of several such factors acting together presumably might reduce LESP enough to produce symptomatic heartburn in the luteal phase more frequently than in the follicular phase of susceptible women. Consistent with such a formulation is our unpublished obslzrvation that female medical students experience symptomatic heartburn more commonly during the latter half of their menstrual cycles (Days 15 to 28, i.e., lutcal phase) than during the immediate postmenstrual period (follicular phase). Specifically, during the prcceeding three years 25 female medical students at the University of Pittsburgh who were not using oral contraceptives agreed to keep a diary of their menstrual cycles and when they experienced symptomatic heartburn. As a result of such cooperation, we have been able to observe these women during a total of 405 complete menstrual cycles. Arbitrarily
dividing each menstrual cycle into follicular phase (Days 1 to 14) and luteal phase (Days 14 to first day of vaginal bleeding) and then assigning each of the 135 documented episodes of heartburn to one or the other two menstrual cycle phases, we found a significant preponderance of symptomatic heartburn episodes during the luteal phase (I/? = 88.8889; p < 0.001) as compared to the follicular phase. The failure to detect a significant difference in basal gastric pH and plasma gastrin levels during the course of this study as well as in previous studies”, 6 tends to negate a role for either of these two factors in the genesis of the observed LESP reduction. In summary, these studies demonstrate that: (1) Basal resting LESP during the luteal phase of the menstrual cycle is reduced in women relative to LESP measurements recorded in the follicular phase, and (2) changes in basal gastric pH and plasma gastrin levels cannot account for this observed decline in LESP during the luteal phase as compared to the follicular phase.
REFERENCES 1. Melton, C. F., Jr.: Electrical activity in the uterus of the rat, Endocrinology 58: 139, 1956. 2. Marshall, J. M.: Effects of estrogen and progesterone on single uterine muscle fiber in the rat, Am. J. Physiol. 197:
935, 1959. 3. Fisher, R. S., Roberts, G. S., Grabowski, C. J., and Cohen, S.: Heartburn of pregnancy: A hormonal disorder, Clin. Res. 23: 284A, 1976. 4. Fisher, R. S., Mayer, E., and Grabowski, C.: Effects oforal contraceptive agents on the lower esophageal sphincter (LES), Clin. Res. 25: 3lOA, 1977. 5. Van Thiel, D. H., Gavaler, J. S., Joshi, S. N., and Stremple, J. F.: Heartburn of pregnancy, Gastroenterology 72: 666, 1977. 6. Van Thiel, D. H.. Gavaler, J. S., and Stremple, J. F.:
Lower esophageal sphincter pressure in women using sequential oral contraceptives, Gastroenterology 71: 232, 1976. 7. Schulze, K., and Christensen, J.: The lower sphincter of the opossum esophagus in pseudopregnancy, Gastroenterology (in press). 8. Yalow, R. S., and Berson, S. A.: Radioimmunoassay of gastrin, Gastroenterology 58: 1, 1970. 9. Hotchkiss, J., Atkinson, L. E., and Knobil, E.: Time course of serum estrogen and LH concentrations during the menstrual cycle of the Rhesus monkey, Endocrinology 89: 117, 1971. 10. Abraham, C. E., Swerdloff, R., Tulchinsky, D., and Odell, W. D.: Radioimmunoassay of plasma progesterone, J, Clin. Endocrinol. Metab. 32: 619, 1977.