Indian J Physiol Pharmacol 1998; 42 (4) : 498-502

EFFECTS OF THE MENSTRUAL CYCLE ON TIMING ANDDEPTH OF BREATHING AT REST

TARUN K. DAS

Department of Physiology,Medical College,Baroda - 390 001

( Received on November 15, 1997)

Abstract: Volume and timing components of resting ventilation weremeasured serially in 40 women aged 18 to 36 yr, during menstrual, follicularand luteal phases of menstrual cycle. Resting minute ventilation (VE) wassignificantly higher (P<O.OOl) in luteal phase than in menstrual andfollicular phases; in the two latter phases VE was almost equal. Thisincrement in V

Eduring the luteal phase was due to a significant rise

(P<O.OOl) in tidal volume (VT ). Respiratory frequency (D was unchangedthroughout the cycle. Although there was a mean increases in inspiratorytime (T,) during the luteal phase compared to the other two phases, thedifference did not reach statistical significance. Duty cycle, T,f T

LoL, was

also unchanged throughout menstrual cycle. However, mean inspiratory

f1ow, VI T" was significantly higher (P<O.05 and P<O.Ol) during lutealphase as compared to that during menstrual or follicular phasesrespectively. Pulmonary mechanics, as measured by forced vital capacity(FVC), forced expiratory volume in one second (FEV,) and forced mid

expiratory f10w rate (FEF2"~.75"')' were within normal limits and remainedunaltered during the menstrual cycle. Therefore, in the absence ofalteration of pulmonary mechanics, the luteal increase in ventilation andinspiratory flow suggests a possible role for progesterone in stimulatingthe respiratory drive, either centrally or through the peripheralchemoreceptors or by both.

Key words: menstrual cyclepulmonary mechanics

INTRODUCTION

It has been reported thathyperventilation and increase in oxygenconsumption occur during the luteal phaseof menstrual cycle and that if pregnancyoccurs, the respiratory stimulationcontinues throughout gestation 0, 2).Probably progesterone plays a key role in

pulmonary ventilationprogesterone

the phenomenon. It is also reported thatthe tendency for central apnea andhypopnea is reduced during pregnancy andthat could be due to increased progesteronelevels (3). However, the mechanism throughwhich endogenous progesterone acts asventilatory stimulus is not confirmed (4).Therefore, the present study of timing anddepth of breathing, which influence

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Indian J Physiol Pharmacol 1998; 42(4)

ventilation, was undertaken to observewhether these indicators alter with thephases of menstrual cycle, particularlyduring luteal phase when the progesteronelevel is normally high.

METHODS

Forty healthy female volunteers, 18-36years of age, were studied throughout theirmenstrual cycle. They were not taking anycontraceptive medication either before orduring the study. Their age, height andweight (mean ± SD) were 22.6 ± 4.21 yr,159.5 ± 4.22 em and 50.8 ± 4.71 kgrespectively. The selection of the subjectswas based on fairly normal and regularmenstrual history (28 ± 2 days cycle).Determination criteria of different phasesof menstrual cycle have been describedearlier 0). In brief, the period of ovulationwas judged from daily basal oraltemperature. Menstrual phase was based onthe subject's statement. Ventilation recordedafter 3-4 days of cessation of the bleeding,on 8th-12th day of the cycle, has been takenas representative for the follicular phaseand that recorded on 20th-24th day of thecycle was taken to be the data for lutealphase.

A closed circuit apparatus, Expirograph(Godart, Holland), containing C02 absorberwas used for measuring ventilation.Emotional and physiological distress wereavoided by allowing a few trials of mouthbreathing through the apparatus with thenose clipped before the day of actual test.The experiment was carried out underalmost similar environmental conditions atthe basal state in morning hours. After 15minutes rest on the actual test day, each

Breathing during Menstrual Cycle 499

subject was studied in sitting position. Afterthe steady state of ventilation measured atslow paper speed (60 mm/min), for theduration of 10 minutes, the timing andvolume for both inspiration and expirationwere measured at high paper speed(1200 mm/min) at least for 10 respiratorycycles. The procedure was repeated on thenext consecutive day. To minimize the effectof training, if at all, the subjects wererandomly allocated to be studied first in anyof the three phases. At the end of 10 minperiod of quiet breathing after the firstexperiment, the forced vital capacity (FVC),forced expiratory volume in first second(FEV) and forced midexpiratory flow rate(FEF 257.-7;;r,1) were recorded in standingposibon in each phase using the sameinstrument after some modifications.

We have measured minute ventilation(V (';) not only in terms of its classicalcomponents, tidal volume (VT) and breathingfrequency (f) from the slow expirogram, butalso in relation to the duration of inspiration(T

j) and the mean inspiratory flow (VT/T,)

as measured from the record taken at highpaper (20 mm/sec) :

VE = VT X f = V.fI'r x T/I'tot X 60 lImin (5, 6).

where Ttot is the average duration of eachbreath (60/f, s) and T/Ttot ' i.e. the proportionof each breath spent on inspiration, istermed as the inspiratory duty ratio (5, 6).All the volumes were expressed in terms ofbody temperature, pressure and saturatedwith water vapour (BTPS).

The values of respiratory timings andflows were averaged from minimum of 10respiratory cycles for each phase. Outcomewas expressed as mean ± SD. The subjectsacted as their own controls; the differences

500 Tarun K Da

in paired values were used for determiningthe statistical significance by Fisher test.The alpha error for a significant test wasset at 5% level.

RESULTS

The minute ventilation with its differentcomponents, timing and depth, and

pulmonary mechanics during differentphases of menstrual cycle are presented inTable 1. Vfo: increased significantly (P<O.Ol)in luteal phase compared to both menstrualand follicular phases. The increase was

Indian J Physiol Pharmacal 1998; 42(4)

Pulmonary mechanics as measured by

FVC, FEV I and FEF~;;"_7;;'/' (Table I) werewithin normal limits and remainedunaltered during different phases ofmenstrual cycle.

The basal oral temperature (OF) recordedduring luteal phase (98.46 ± 0.26) wassignificantly higher (P<O.OOl) than thatduring either menstrual (97.71 ± 0.53) orfollicular (97.76 ± 0.41) phase. The increasein basal body temperature during lutealphase in each subject indicates that thecycles were ovulatory.

TABLE I: Pulnonary ventilation ami mechanics during menstrual cycle (n = 40).

Ventialtion

f,lmillVT mLV~, LlminT;: ST/T,,,,,V/Tr' Lis

Mechanics

FVC, LFEV" LFEV""'_7;" LIs

!vIenstrual phase

17.70±6.07581±196

9.76±3.761.67±0.860.43±0.050.37 ±O 14

2.7:l±0.402.40±0.313.01±070

Follicualr phase

18.00±6.60591±213

9.79±2641. 70± 0.850.44±0060.36±0.10

2.68±O.322.38±0.313.04±0.64

Luteal ph ase

17.10±6.22697±220**

10.88±285~

1.83±1.100.43±O.040.4l±0.10·

2.70±0.342.41±0.283.08±0.70

Data are presented as mean ± 3D. +P<0.05, *P<0.01, "P<O.OOl compared with the values of menstrual andfollicular phases.

almost 12 percent. This increment in VI' wasbasically due to significant (P<O.OOll risein VT . The f remained unchanged, as derivedfrom Trot' Although there was an incpasein T I noted during the luteal phase, thedifference did not reach statisticalsignificance. Duty cycle, T/Tt'i' was alsounchanged. Mean inspiratory Cow, V/TI'was significantly increased in lut al phas·'as compared to that in m nstrual andfollicular phases (P<0.05 and P<O.Olrespecti vely).

DISCUSSION

Normal ventilation is a complex processinvolving several interactions. Behavioural,chemical and central neuromuscular drivesinfluence breathing profoundly. The alteredstate of breathing during menstrual cycleprobably involves all or ny suchmechanisms. Earlier studies indi ate, thathyp(~rventilation eluring lut al phase ofmenstrual cycle and during pregnancy areassociated with increased progesterone

Indian J Physial Pharmacal 1998; 42(4)

concentration 0, 2). Further, administrationof progesterone to normal men andpost menopausal women produceshyperventilation (7, 8). Progesterone hasalso been used for treating hypoventilatingpatients (9, 10). In this study, significantincrease (P<O.OI) in minute ventilation wasnoted during luteal phase compared to bothmenstrual and follicular phases. Ventilationduring the two latter phases was almostequal. Hyperventilation during the lutealphase was significantly rise in VT only,without any appreciable change inrespiratory rate. Inspiratory time did notchange significantly, although a gradualincrease from menstrual to luteal phase wasnoted. Therefore, the larger VTwas due toan increase in inspiratory flow, V/T I. Thevariables, VT/T

jand T/T tot have been

interpreted as drive and timing componentsof ventilation which may be independentlycontrolled (11). The central inspiratoryneural drive can be assessed bymeasurement of V/T lor by mouth occlusionpressure (POI)' which is the inspiratorypressure generated at the end of 0.1 secafter the beginning of inspiratory efforts.The V/T I are dependent on, and affectedby, changes in pulmonary mechanics,whereas POI is independent of themechanical properties of respiratory system(2). Although we have not measured POI'our observation of FVC, FEV I, and FEF 2;'1.

75'/' in the same subjects during each phasereflect the unchanged mechanical propertiesof lungs during the menstrual cycle. FEV Iin faet is the measure of flow rate duringthe fii'S t s eco nd of forced expi ra toryspirography. It includes sufficient flows atlower lung volumes to reflect the smallairway patency in addition to large airwaychanges. Thus increase in inspiratory flow(ViT I) during luteal phase, without any

Breathing during Menstrual Cycle 501

alteration is pulmonary mechanics, mainlyindicates an augmented central ventilatorydrive, although the role of peripheralchemoreceptor can not be entirely ruled out.However, evidences suggest that both lutelphase of menstrual cycled and pregnancyare associated with central ventilatory driveas indicated by increase in mouth occlusionpressure (4,13). In this study effective time

ratio or duty cycle, T /Ttot ' was essentiallyunchanged. This indicates that inspiratorymuscle activity probably did not alter duringthe menstrual cycle. Present observationsupports earlier findings of unchangedeffective time ratio and respiratory musclestrength during menstrual cycle (14).

Increase in brain adrenergic receptorsduring pregnancy is associated withbehavioural changes which can modifyventilation (15). Recently it has beenreported that luteal phase of menstrual

cycle is also associated with increasedadrenoreceptor density (16). However, toassess respiratory control at its mostphysiological and with least interferencefrom behavioural influences, the emphasishas shifted away from stimulation byhypercapnia and hypoxaemia to moredetailed analysis of resting breathing (17).The usual causes of hyperventilationassociated with disease are absent as our

all subjects were healthy. Probably therewas not even an enlargement of dead space,

which can influence ventilation, as theventilation was augmented mainly by tidalvolume rather than respiratory rate. Thishyperventilation could be attributed toprogesterone, as it was observed only duringthe luteal phase of menstrual cycle. Further,several evidences suggest thatadministration of progesterone to

502 Tarun K Das

volunteers, both male and female, and topatients with alveolar hypoventilationsyndrome, increases ventilation 00,18). Thesits of action of progesterone is thought tobe either the respiratory center orperipheral chemoreceptors, or a combinationof both. There may be a threshold to pC02and hence an increase in peripheralchemoreceptor sensitivity (4,19). The centralchemoreceptor stimulation has an importantinfluence on cholinergic outflow of theairways (20). It may cause reflex increasein ventilation and hypocarbia III

Indian J Physiol Pharmacol 1998; 42(4)

spontaneously breathing subjects withhypoxic bronchoconstriction (21).

In conclusion, our finding in healthysubjects demonstrate that hyperventilationduring luteal phase is associated with anincrease in inspiratory flow without anyalteration in pulmonary mechanics. Thisstudy also suggests the possible mechanismof decrease in carbon dioxide tension inblood after hyperventilation induced bysynthetic progesterone in patients withobstructive pulmonary disease (22).

REFERENCES

1. Das TK, Jana H. Basal oxygen consumption duringdifferent phases of menstrual cycle. Indian J MedRes 1991; 94: 16-19.

2. Milne JA. The respiratory response to pregnancy.Pustgrad Med J 1979; 55: 318-324.

3. Brownell LG, West P, Kryger MH. Breathingduring sleep in normal pregnant women. Am RevRespir Dis 1986; 133: 38-41.

4. Contreras G, Gutierrez M, Beroiza T, Fantin A,Oddo H, Villarroel L, Cruz E, Lisoba C. Ventilatorydrive and respiratory muscle function in pregnancy.Am Rev Respir Dis 1991; 144: 837-841.

5. Clark FJ, VonEuler C. On the regulation of depthand rate of breathing. J Physiol 1972; 222: 267­295.

6. Milic Emili J, Grunstein MM. Drive and timingcomponents of ventilation. Chest 1976;70 Suppl. 1:131-133.

7. Mikami M, Tatsumi K, Kimura Honda Y, KuriyamaT. Respiration effect of synthetic progestin in smalldoes in normal men. Chest 1989; 96: 1073-1075.

8. Smith CA. Progesterone and control of breathing.Dissertation Abstracts International. D. TheSciences and Engineering 1978; 39: 3178-3179.

9. Lyons HA, Huang CT. Therapeutic effect ofprogesterone in alveolar hypoventilation associatedwith obesity. Am J Med 1968; 44: 881-888.

10. Sutton FD, Zwillich CW, Creagh CE, Pierson OJ.Wiel, JV. Progesterone for outpatient treatment ofpickwickian syndrome. Annals Intern Med 1975;83: 476-479.

11. Gibson GJ. Tests of ventilatory control. In: Clinicaltests of respiratory function. Raven Press, NewYork, 1984: 107.

12. Burki NK. Measurements of ventilatory regulation.Clinics in Chest Medicine 1989; 10: 215-226.

13. Schoene RB, Robertson HT, Pierson DJ, PetersonAP. Respiratory drives and exercise in menstrualcycles of athletic and non athletic women. J ApplPhysiol 1981; 50: 1300-1305.

14. Chen H, Tang Y. Effects of menstrual cycle onrespiratory muscle function. Am Rev Respir Dis1989; 140: 1359-1362.

15. Smiley RM, Finster M. 00 receptors get pregnanttoo? Adrenergic receptors alterations in humanpregnancy. J Maternal Fetal Med 1996; 5: 106-114.

16. Tan KS, Mcfarlane LC, Lipworth BJ. Betaadrenoreceptor regulation and AMP reactivityduring the menstrual cycle in female asthmatics.Thorax 1995; 50 Suppl 2: 60.

17. Milic Emili J. Recent advances in clinicalassessment of control'of breathing. Lung 1982; 160:1-17.

18. Goodland RL, Reynolds JG, McCord AB,Pommeren'ke WT. Respiratory and electrolyteeffects inel uced by estrogen and progesterone. FertSteril 1953; 4: 300-317.

19. Hannhart B, Pickett CK, Moore LG. Effects ofestrogen and progesterone on carotid body neuraloutput responsiveness to hypoxia. J Appl Physiol1990; 68: 1909-1916.

20. Mitchell RA, Herbert DA, Baker DG. Inspiratoryrhythm in airway smooth muscle tone. J ApplPhysiol 1985; 58: 911-920.

21. Perez Fontan JJ. Mechanical function of the lungsand airways during hypoxia. In: Tissue oxygendeprivation. From molecular to integrated function.Eds by Haddad GG, Lister G. Marcel Dekker Inc.,New York 1996: 340.

22. Skatrud JB, Dempsey JA. Relative effectiveness ofacetazolamide versus medroxyprogesterone acetatein correction of chronic carbondioxide retention.Am Rev Respir Dis 1983; 127: 405-412.