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Obstetrics & Gynecology 1999;94:232-237
© 1999 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Effect of Vulvovaginal Estrogen on Sensorimotor Response of the Lower Genital Tract: A Randomized Controlled Trial

DAVID C. FOSTER, MD, MPH, MARY PALMER, PhD, RNC and JANE MARKS, RN

From the Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York; University of Maryland School of Nursing, Baltimore, Maryland; and The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address reprint requests to: David C. Foster, MD, MPH Department of Obstetrics and Gynecology University of Rochester, PO Box 668 601 Elmwood Avenue Rochester, NY 14642 E-mail: dfoster{at}obgyn.rochester.edu


   Abstract
Top
Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objective: To assess the effect of vulvovaginal estrogen on mucocutaneous sensory threshold and circumvaginal motor strength.

Methods: Thirty-nine postmenopausal, hypoestrogenic women with mixed lower-genitourinary-tract complaints were placed in four masked treatment arms by permuted-block randomization for 6 weeks. One group received topical estradiol (E2) cream and pelvic muscle biofeedback training, the second received topical cream and sham E2 biofeedback, the third received placebo cream and pelvic muscle biofeedback training, and the fourth received placebo cream and sham biofeedback. Circumvaginal muscle strength was measured by averaging maximum intravaginal pressure (mmHg) generated over a set of four pelvic muscle contractions. Absolute changes in von Frey threshold (mN) and maximum intravaginal pressure (mmHg) over 4 and 6 weeks were reported as summary measures. Of 39 subjects, 30 completed the study.

Results: Topical estradiol cream significantly improved mechanical sensitivity of the vulvar vestibule to von Frey hairs, a -1.2-mN threshold decrease at 4 weeks (F = 10.29; P = .004), and a -1.6-mN threshold decrease at 6 weeks (F = 8.24; P = .009) compared with placebo cream. Stratification by age showed significantly greater improvement in mechanical sensitivity in the older (70–79 years) age group randomized to estrogen cream and a -5.49-mN threshold reduction (F = 17.65; P = .002). Maximum intravaginal pressures during circumvaginal muscle contraction did not differ between estrogen and placebo cream users (F = 0.00; P = .99).

Conclusion: Improved sensation to mechanical stimuli can result from a rapidly acting, direct effect of topical E2 cream on the vulvar vestibule.

Estrogen replacement therapy (ERT) provides widely recognized benefits in the lower urogenital tract of postmenopausal women, although the mechanism of its action is poorly understood. Whereas the effect of estrogen on epithelial proliferation of the vagina has been known for 50 years, studies of estrogen’s potential benefit to sensorimotor function in postmenopausal women remained limited.1 Benefits of ERT for urinary complaints of urgency, frequency, and nocturia were reported even when there were no changes in formal urodynamic studies.2,3 A higher portion of estrogen-supplemented, postmenopausal women showed positive bulbocavernosus reflexes than placebo-treated women, which Fantl et al3 suggested might be due to increased sensory responsiveness. Studies in premenopausal women on the effects of estrogen on cutaneous and soft-tissue pain thresholds reported heightened sensitivity of cutaneous threshold at midcycle.4 In a study using rats after ovariectomy, estrogen enlarged the sensory field innervated by the pudendal nerve.5 In terms of motor function, the effect of estrogen upon striated muscles such as the levator ani remains unclear. Reports are equivocal about estrogen receptors in the levator ani and whether estrogen replacement improves strength of striated muscle after menopause.6,7

This report originated from a larger study, to be published later, of the effects of estrogen and pelvic muscle exercises on the lower urogenital tracts of post-menopausal women. In the present study, we tested the hypothesis that topical estrogen directly increases vulvovaginal sensory responsiveness to mechanical stimuli and improves strength of circumvaginal muscles.


   Materials and Methods
Top
Abstract
 Materials and Methods
Results
 Discussion
 References
 
We recruited community-dwelling, postmenopausal women from the Baltimore–Washington, DC, metropolitan area. Eligible women were 60 years or older, with urinary tract complaints including incontinence, urgency, or frequency. Before entering the study, candidates had urologic assessments according to the Agency for Health Care Policy and Research Clinical Practice Guideline8 and were instructed to abstain from estrogen within 3 months of study entry. Exclusion criteria included prior thrombosis, myocardial infarction, ischemic heart disease, cerebrovascular accident, estrogen dependent neoplasia, cervical dysplasia, active cholecystitis, uncontrolled diabetes mellitus, active liver disease, or an abnormality on mammogram at study entry. Recruitment spanned 3 years from July 1, 1993, to June 30, 1996. Primary outcome measures for this report included vulvar sensation by von Frey hairs and maximal intravaginal pressure change during pelvic floor exercise. von Frey hairs (Stoelting, Wood Dale, IL) are graduated mucocutaneous stimuli that cause reproducible mechanical force. Secondary outcome variables included maturation index, vaginal atrophic index, and serum estradiol (E2). The study protocol was reviewed and approved by the Johns Hopkins Joint Committee on Clinical Investigation.

During first prerandomization visits, we obtained informed written consents and administered quality-of-life questionnaires. At second prerandomization visits, progesterone challenge tests were given to women with intact uteri. At randomization visits, we did physical examinations, including evaluations of pelvic support defects, status of bulbocavernosus reflex, vaginal atrophic indices,9 and perineal sensations by von Frey hairs. Vaginal atrophic index is a prevalidated measure of skin elasticity and turgor, quantity of pubic hair, disappearance of labia minora, breadth of introitus, and vaginal depth with a score range of 6 units (high atrophy) to 15 units (low atrophy). Laboratory tests for this report included maturation index by vaginal cytology reported as percentage parabasal/intermediate/ superficial cells, and serum E2 in picograms per milliliter. In the event of uterine bleeding after progesterone challenge, we planned an endometrial biopsy and a decision for study continuation by a designated physician independent of the study.

Appropriate subjects were randomized by permuted-block randomization into one of four treatment arms for 6 weeks: E2–biofeedback group received topical E2 cream, 2 g (0.2 mg E2), and a standard regimen of pelvic muscle biofeedback; E2–no biofeedback group received topical E2 cream 2 g (0.2 mg E2), and sham biofeedback in the form of a quality-of-life questionnaire that matched number and duration of visits of the biofeedback groups; placebo cream–biofeedback group received placebo cream and had the standard regimen of pelvic muscle biofeedback; and placebo cream–no biofeedback group received placebo cream and sham biofeedback as described above. Computer-generated random numbers were used for group assignments. The E2–placebo cream treatment arms were double-masked using identical tubes packaged with corresponding subject study numbers. All women were instructed to apply 2 g of cream to the vulvar vestibule and vagina nightly before sleep for weeks 1 and 2, three times weekly for weeks 3 and 4, and two times weekly for weeks 5 and 6. By necessity, the pelvic muscle education treatment arms were masked only to the researchers doing and analyzing threshold testing. At postrandomization weeks 4 and 6, all subjects had follow-up testing of perineal sensation by von Frey hairs, vaginal atrophic index, maturation index, and serum E2. von Frey hairs (Stoelting) were calibrated according to published work.10 Stimulus force was reported in terms of millinewtons that were calibrated with a balance and determined to provide 0.35, 0.84, 1.27, 1.34, 2.29, 4.09, 5.35, 6.98, 7.3, 9.12, and 12.0 mN. We followed a standard technique previously described for determination of von Frey mechanoreceptive thresholds.11 Out of view of the study subject, the hair was repeatedly prodded roughly perpendicular to the mucosal surface. The movement of the handle of the von Frey hair was continued for 3 to 5 mm from the instant that the hair made contact with the mucosa. The target mucosa was defined as the lower half of the vulvar vestibule delimited by Hart’s line and the carunculae hymenalis. An independent observer confirmed that threshold testing technique was uniform. Interrater reliability of von Frey threshold technique produced a percentage agreement of 0.90, considered acceptable. Changes in mechanoreceptive thresholds were calculated by subtracting baseline threshold from measurements at postrandomization weeks 4 and 6.

Subjects assigned to pelvic muscle exercises had 40-minute biofeedback sessions with a research nurse at postrandomization weeks 0, 4, and 6 and received written instructions for home training. Pelvic-muscle-exercise subjects received visual feedback about magnitude of contractions of the pelvic floor and abdominal muscles. The resting pressure of the intravaginal probe (Incare Intravaginal Balloon; Hollister Inc, Libertyville, IL) was adjusted, with injection of air, to a necessary distension to maintain the balloon device intravaginally. Resting balloon pressure was dependent upon individual resting vaginal tonus and subject comfort. Intravaginal balloons were attached to an in-line pressure transducer and processing unit (Incare PRS 8900; Hollister Inc). During initialization of a biofeedback session, the instrument design would recalibrate intravaginal resting pressures to 0 cm H2O. Each biofeedback session consisted of four exercises of four contractions each, totaling 16 contractions per session. Within each session, the four exercise cycles were preceded by reestablishment of resting pressure at zero baseline. The duration of circumvaginal contractions was identical between subjects during each session. Over subsequent sessions, the research nurse encouraged consistent increases in duration of circumvaginal contractions. Maximum intravaginal pressures during contractions were calculated as the difference between maximum pressure (in centimeters of H2O) and the adjusted resting pressure of 0 cm H2O, averaged over four circumvaginal muscle contractions. Maximum intravaginal pressures were averaged (four contractions per set) during each of five exercise sets of a training session. Pressure units, initially recorded in centimeters of H2O, were converted to mmHg for comparison with previous studies.12–17 Subjects randomized to sham biofeedback received quality-of-life questionnaires at weeks 0, 4, and 6. The responses to the quality-of-life questionnaire were reviewed with the sham biofeedback subjects to make the visit time similar to a biofeedback session. To remove the possibility of a biofeedback training effect, sham biofeedback subjects did not undergo baseline circumvaginal muscle studies.

Statistical analysis was done in two parts. Demographics, baseline laboratory values, and unadjusted outcome values were reported in terms of proportions, means, and standard deviations. We analyzed proportions by {chi}2 and Fisher exact test, where appropriate. Measures of estrogen effect included changes in maturation index, serum E2, and vaginal atrophic index, and were correlated with changes in mechanoreceptive thresholds. Unadjusted absolute values for von Frey threshold and maximum intravaginal pressure were compared for subjects receiving estrogen and placebo cream at randomization, week 4, and week 6. For reporting repeated measures within subjects, we calculated summary measures, mean change in von Frey sensroy threshold (mN), and circumvaginal muscle strength (mmHg) for the intervals of randomization weeks 4 and 6. Univariate analysis of variance was done on the summary measures with estrogen cream as the single independent variable. The summary measure for von Frey threshold change was also stratified into 60–69 year and 70–79 year age groups. Analysis of variance compared pairwise absolute differences from randomization to week 4 and from randomization to week 6 separately. The null hypothesis stated that active treatment did not significantly differ from placebo in terms of variance of summary measures for von Frey sensory threshold and circumvaginal muscle strength. We analyzed subjects who completed the study; therefore, our analysis was not on the basis of intention to treat. Statistical analysis used the STATA statistical package (STATA Corp, College Station, TX). Significance was P < .05 using a two-tailed test. We lacked preexisting data to estimate appropriate numbers of subjects in each treatment arm for acceptable statistical power. We decided that a total recruitment of 60 subjects, 15 per treatment arm, was within our time and budgetary limitations.


   Results
Top
Abstract
 Materials and Methods
 Results
Discussion
 References
 
Table 1Go compares baseline characteristics of the four treatment groups. Fifty-one women attended prerandomization visits, 39 were randomized into one of four treatment groups, and 30 completed the requisite visits needed for analysis. We did not achieve our desired 60 subjects, owing to inability to fully recruit within the 3-year period. Randomized subjects who dropped out of the study prematurely were distributed between all treatment groups, without a common cause for dropout. Analysis by intention to treat was not possible because of a lack of sensorimotor data from weeks 4 and 6 of dropout subjects. Age of subjects ranged 60–72 years, and duration of menopause ranged from 21–26 years. The E2–biofeedback and E2–no biofeedback groups had higher mean parity (4.0 and 3.5, respectively) than the placebo cream–biofeedback and placebo cream–no biofeedback groups (2.0 and 2.9, respectively), but differences were not statistically significant. The predominant urinary tract complaint was incontinence in 71–100% of each group. Other variables including history of vaginal surgery, vaginal atrophic index, maximum intravaginal pressure, and serum E2 did not differ significantly between groups at baseline. At baseline, the E2–biofeedback and E2–no biofeedback groups had higher mean von Frey sensory thresholds (2.4 and 3.8 mN, respectively) than the placebo cream–biofeedback and placebo cream–no biofeedback groups (1.3 and 1.9 mN, respectively), but differences were not statistically significant. When analyzing baseline E2 levels, we found a single outlier of 81.0 pg/mL in the placebo cream–biofeedback group. Because of possible unrecognized exogenous estrogen use, that subject was removed from statistical analysis of the primary outcome variables. None of the subjects with intact uteri had bleeding after progesterone challenge.


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  		Table 1. Baseline Characteristics and Response to Treatment by Group
 
Table 2Go presents the primary outcome variables, unadjusted mean values, and mean change for von Frey threshold and maximum intravaginal pressure over baseline, 4 weeks, and 6 weeks of topical cream use. Topical E2 cream significantly improved mechanical sensitivity of the vulvar vestibule to von Frey hair testing, a -1.22-mN threshold decrease at 4 weeks (F = 10.29; P = .004) and -1.6-mN decrease at 6 weeks F = 8.24; P = .009) compared with placebo cream. Stratification by age showed significantly greater improvement in mechanical sensitivity of the vulvar vestibule in the oldest (70–79-year) age group randomized to E2 cream, -5.49-mN threshold reduction (F = 17.65; P = .002). The mean maximum circumvaginal muscle contraction ranged from 22 to 40 mmHg during training sessions. Maximum intravaginal pressures during circumvaginal muscle contractions did not differ between E2 cream (+1.1 ± 4 mmHg) and placebo cream users (-7.3 ± 6 mmHg; F = 0.00; P = .99). Stratification of maximum intravaginal pressure by age was not done owing to inadequate subject numbers per cell.


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  		Table 2. Mean Change in von Frey Threshold and Circumvaginal Contraction at Baseline, 4 Weeks and 6 Weeks
 
Topical E2 cream resulted in significant disappearance of parabasal cells (0% on maturation index, Fisher exact test; P = .05), and significantly improved (increased) vaginal atrophic index compared with placebo (F = 5.77; P = .03). The scatterplot of serum E2 and mechanoreceptor threshold is shown in Figure 1Go. We found a wide dispersion of values for serum estradiol in the scatterplot and could not find a dose–response relationship between serum E2 and the mechanoreceptor threshold (r = -0.18; P = .50). We also could not find a significant relationship between vaginal atrophic index and mechanoreceptor threshold (r = -0.03; P = .90).



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  		Figure 1. Scatterplot of serum estradiol change by von Frey threshold change over the 6-week clinical trial.

 

   Discussion
Top
Abstract
 Materials and Methods
 Results
 Discussion
References
 
Despite clinical acceptance that estrogen improves post-menopausal symptoms of the lower genitourinary tract, measurable physiologic change of genital tract is limited. Topical estrogen in postmenopausal women increased the positive bulbocavernosus reflex without changing other formal urodynamic measures.3 We found a rapid improvement in sensitivity of mechanoreceptors of the vulvar vestibule after 4 weeks of topical estrogen cream and even greater improvement after 6 weeks of topical estrogen. We could not show a change in circumvaginal motor strength with the use of topical estrogen cream. Our findings support the suggestion of Fantl et al3 that changes observed in the bulbocavernous reflex with topical estrogen might be based on sensory rather than motor changes. Improved mechanical sensitivity to the vulvar vestibule might contribute to improved sexual responsiveness in estrogen-supplemented, postmenopausal women. Suggested factors that improved sexual function through estrogen replacement therapy (ERT), well summarized by Sarrel,18 include increased blood flow, prevention of genital atrophy, and maintenance of peripheral sensory perception. Much research on the neurobiologic effects of estrogen has focused on the central nervous system (CNS). Although we cannot discount the possibility that topical estrogen works centrally, we suggest that estrogen might also exert a local sensorineural effect. Data on the effects of estrogen on human peripheral nerves are limited. In animal models, estrogen increases the mechanoreceptive field of the pudendal nerve and increases mechanoreceptor-associated allodynia.5,19,20 Within the vulvar vestibule, the two potential sensorineural targets for estrogen are the C fiber and the Merkel cell. Merkel receptors are classified as slow-adapting fibers that demonstrate a mechanical threshold of 0.5–1.5 mn. Mechanical thresholds of subjects taking estrogen, found in the present study, fell within the range of the Merkel cell rather than the higher threshold nociceptors (C fibers).11 However, estrogen receptors within Merkel cells have not been reported. Mechanoreceptor sensitivity might also be influenced locally by indirect factors including skin compliance and blood flow. The increase in epithelial thickness shown by maturation index makes likely a decrease in mucocutaneous compliance in the vulvar vestibule. Blood flow was shown to increase in the genital region after estrogen replacement and could potentially improve oxidative metabolism of sensory receptors.18 Confirmation of a direct effect upon sensory receptors will need further functional and histological characterization of estrogen action.

The muscle-strengthening effects of ERT, specifically upon circumvaginal muscles, was not statistically significant in our study. In prior studies, Phillips found that ERT protected against loss of maximum voluntary force per cross-sectional area of the abductor pollices muscle in postmenopausal women.21 Taaffe et al7 could not show an effect on lower body muscle strength relative to lean body mass in postmenopausal women receiving ERT. The two studies differed in the technique of measurement of motor strength, which could have contributed to the differences in results. Schellart et al22 recently reported that ERT produced no effects on manometric parameters of the external anal sphincter, but that report can be criticized for a small sample (n = 5). Although our study concurs with Schellart’s findings of no effect of estrogen upon circumvaginal muscles, both studies suffer from small samples and lack of standardized techniques to measure muscle strength of the pelvic floor. A valid and reliable instrument to evaluate pelvic floor musculature is needed for pelvic floor physiology study. Although the Kegel perineometer has been available for 50 years, the lack of a standard measurement technique results in unclear test validity and reliability. Six investigations using the Kegel perineometer reported resting pressures ranging from 5 to 20 mmHg and maximum contraction pressures ranging from 15 to 50 mmHg.13–17 In an attempt to develop a reliable and valid research tool, Dougherty et al13 fabricated an intravaginal balloon for each study subject and measured circumvaginal pressures in a well-controlled setting. Of four variables tested by Dougherty et al (resting pressure, rate of rise, maximal pressure, and rate of return to baseline), maximal pressure had the best test–retest reliability (r = 0.85; P < .05). With reliable findings of previous work, our study reported maximum intravaginal pressure and was similar to the results of Dougherty et al. Our reported mean maximal contraction in terms of mmHg pressure fell within the pressure range of other studies.13–17,20

Owing to a small sample, our conclusions concerning ERT effects risk type I and type II statistical errors. As in Table 1Go, subjects randomized to active estrogen cream reported higher (less sensitive) thresholds to von Frey hairs at baseline testing than subjects randomized to placebo cream. The distribution of subjects, small sample, and repeated within-subject measurements could make the ERT group show a greater improvement in sensory threshold, based on the statistical phenomenon of regression to the mean. In addition, our two-by-two design reduced the number of subjects having circum-vaginal muscle pressure measurement to one half the number of subjects having von Frey threshold testing. Therefore, our design reduced the power to find a statistically significant difference for circumvaginal muscle strength compared with von Frey threshold testing. Our conclusions are strengthened by a number of findings. We found a good statistical strength of association, a consistant trend of estrogen effect from 4 to 6 weeks of therapy, and an augmented effect in older subjects. Nevertheless, our results should be considered pilot data that will need confirmation by studies with larger samples.

Research on the neurobiologic effects of estrogen has focused on the CNS in terms of complex behaviors, cognition, and memory. The present study suggests indirectly that estrogen might augment the sensory arm of the peripheral nervous system. Further improvement of techniques for measurement of sensory threshold in the lower genital tract will be necessary to confirm estrogen’s effect on the sensorineural arm of the bulbocavernosus reflex and support a peripheral as well as central effect of ERT.


   Footnotes
 
Supported by the National Institutes of Health, National Institute of Nursing Research, Division of Intramural Research.

PII S0029-7844(99)00264-1

Received May 11, 1998. Received in revised form December 30, 1998. Accepted February 3, 1999.


   References
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Abstract
 Materials and Methods
 Results
 Discussion
 References
 
1. Del Castillo EB, Argonz J, Gali Mainini CG. Cytological cycle of the urinary sediment and its parallelism with the vaginal cycle. J Clin Endocrinol 1948;8:76–87.

2. Hilton P, Stanton SL. The use of intravaginal oestrogen cream in genuine stress incontinence. Br J Obstet Gynaecol 1983;90:940–4.[Medline]

3. Fantl JA, Wyman JF, Anderson RL, Matt DW, Bump RC. Post-menopausal urinary incontinence: Comparison between non-estrogen-supplemented and estrogen-supplemented women. Obstet Gynecol 1988;71:823–8.[Abstract]

4. Giamberardino MA, Berkley KJ, Iezzi S, de Bigontina P, Vecchiet L. Pain threshold variations in somatic wall tissues as a function of menstrual cycle, segmental site, and tissue depth in non-dysmenorrheic women and mean, dysmenorrheic women and men. Pain 1997;71:187–97.[Medline]

5. Komisaruk BR, Adler NT, Hutchinson J. Genital sensory field: Enlargement by estrogen treatment in female rats. Science 1972; 178:1295–8.[Abstract/Free Full Text]

6. Phillips SK, Rook KM, Siddle NC, Bruce SA, Woledge RC. Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy. Clin Sci (Colch) 1993;84:95–8.[Medline]

7. Taaffe DR, Luz-Villa M, Delay R, Marcus R. Maximal muscle strength of elderly women is not influenced by oestrogen status. Age Ageing 1995;24:329–33.[Abstract/Free Full Text]

8. Agency for Health Care Policy and Research. Urinary incontinence in adults. 1992; Pub. No. AHCPR 92-0040.

9. Leiblum S, Bachmann G, Kemmann E, Colburn D, Swartzman L. Vaginal atrophy in the postmenopausal woman. The importance of sexual activity and hormones. JAMA 1983;249:2195–8.[Abstract]

10. Treede RD, Meyer RA, Campbell JN. Comparison of heat and mechanical receptive fields of cutaneous C-fiber nociceptors in monkey. J Neurophysiol 1990;64:1502–13.[Abstract/Free Full Text]

11. Johansson RS, Vallbo AB, Westling G. Thresholds of mechanosensitive afferents in the human hand as measured with von Frey hairs. Brain Res 1980;184:343–51.[Medline]

12. Hamann W. Mammalian cutaneous mechanoreceptors. Prog Biophys Mol Biol 1995;64:81–104.[Medline]

13. Dougherty MC, Abrams R, McKey PL. An instrument to assess the dynamic characteristics of the circumvaginal musculature. Nur Res 1986;35:202–6.

14. Skinner DP, Crighton D. Stress incontinence: A comparative racial study. Med Proc 1963;9:189–94.

15. Logan TG. The vaginal clasp. A method of comparing contractions across subjects. J Sex Res 1975;11:353–8.[Medline]

16. Levitt EE, Konovsky M, Freese MP, Thompson JF. Intravaginal pressure assessed by the Kegel perineometer. Arch Sex Behav 1975;8:424–50.

17. Graber B, Kline-Graber G. Female orgasm: Role of the pubococcygeus muscle. J Clin Psychiatry 1979;40:348–51.[Medline]

18. Sarrel P. Sexuality. In: Studd JW, Whitehead MI, eds. The menopause. Oxford, United Kingdom: Blackwell Scientific Publishers, 1988:65–75.

19. Coyle DE, Sehlhorst CS, Mascari C. Female rats are more susceptible to the development of neuropathic pain using the partial sciatic nerve ligation (PSNL) model. Neurosci Lett 1995;186:135–8.[Medline]

20. Coyle DE, Sehlhorst CS, Behbehani MM. Intact female rats are more susceptible to the development of tactile allodynia than ovariectomized female rats following partial sciatic nerve ligation (PSNL). Neurosci Lett 1996;203:37–40.[Medline]

21. Schellart RP, Schouten WR, Huikeshoven FJ. Anorectal manometry before, during and after estrogen replacement therapy. Int Urogynecol J Pelvic Floor Dysfunct 1996;7:77–80.[Medline]

22. Henderson JS. Effects of a prenatal teaching program on postpartum regeneration of the pubococcygeal muscle. JOGN Nursing 1983;12:403–8.




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