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Urogenital aging—Creation of improved awareness
Urogenital aging—Creation of improved awareness Martina Dören, MD, PhD Münster, Germany Urogenital aging is given a low priority in the medical community and is an entity not well known to the general public. Many women are not aware of the possible disorders of the lower urinary tract and the vagina because of estrogen deficiency. These changes are perceived often as a normal part of the general aging process not associated with the possibility of medical attention, diagnosis, and treatment. Access to the information that certain urogenital dysfunctions, in particular incontinence, and vaginal discomfort respond to estrogen replacement therapy is not available for every woman. In addition, physicians and patients may hesitate to address these issues because of feelings of shame and embarrassment, feelings commonly encountered and specific for the complex of urogenital aging. Educational efforts and promotion of information with use of various media might help to improve knowledge and remove the taboo attached to urogenital aging in both health care providers and the general public. Thus a better understanding of urogenital aging would be achieved and the potential of estrogen replacement extended. (Am J Obstet Gynecol 1998;178:S254-6.)
Key words: Urogenital aging, estrogen deficiency, estrogen replacement therapy, women’s health
Menopause research is often associated with metric studies to assess, for example, the future fracture risk of postmenopausal osteoporosis or of major cardiovascular disease, to name only two examples. It is well known that symptoms of urgency, frequency, urinary incontinence, vaginal dryness, and related sexual problems develop in many menopausal women. The presentation of these symptoms is variable and often insidious; most often the symptoms tend to deteriorate with increasing age and may persist throughout life. This development over time suggests a relationship to menopausal estrogen deficiency.1-4 However, the distinctive role of estrogen deficiency in the pathogenesis of urogenital symptoms compared with that of the aging process per se is incompletely understood. Less research attention has been paid to lower urinary tract dysfunction and vaginal health in postmenopausal women as revealed by the selection of major topics of meetings dedicated to various areas of research on the menopause and basic and advanced medical training. Estrogen replacement therapy subjectively improves urinary incontinence5, 6 (Table I) and symptoms resulting from vaginal atrophy.10-15 However, more conclusive research data and in particular randomized, controlled long-term trials to substantiate benefits of estrogen treatment for urogenital health and in particular specific quality of life assessments are certainly welcome. The lack of this knowledge compared From the Department of Obstetrics and Gynecology, Westfälische Wilhelms–Universität Münster. Reprint requests: Martina Dören, MD, PhD, Universitäts-Frauenklinik Münster, Albert-Schweitzer-Str. 33, D-48129 Münster, Germany. Copyright © 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/0/88101
S254
with other areas of menopausal research is apparently linked to the insufficient awareness of the complex of urogenital aging even among physicians. Additional training to thus create awareness of health care providers for urogenital disorders should not only be offered to general practitioners, gynecologists, or urologists but start in medical schools as part of a women’s health teaching program. How relevant are disorders named urogenital aging? Feelings of vaginal discomfort, dyspareunia, and declining interest and activity in sex are complaints increasingly found in the period of the menopausal transition and thereafter. A telephone survey conducted in the United States revealed that one third of women aged 45 to 60 years complained of distressing changes in sexual function.16 According to epidemiologic studies, urinary incontinence and urinary tract infections are very common disorders in postmenopausal women17 and increase with age.18 One of the earliest—and largest—surveys conducted in elderly and very old women in Sweden clearly demonstrated that urinary incontinence and urinary tract infection are a most frequent complaint, thus an important medical problem (Fig. 1). Statistical figures generated in epidemiologic studies may need careful interpretation because the willingness and frequency to communicate the lack of urogenital well-being and related medical attention may be influenced by the cultural and social background of an individual postmenopausal woman. This latter aspect may help to explain why symptoms such as a decrease of libido and vaginal dryness are not necessarily frequently reported by a majority of perimenopausal and postmenopausal women as assessed in major epidemiologic surveys
Dören S255
Volume 178, Number 5 Am J Obstet Gynecol
Fig. 1. Postal survey in Gothenburg, Sweden, of 4206 women aged 65 to 85 years in 1979 (data from reference 18).
Fig. 2. Consultations for menopausal-postmenopausal symptoms over period of 6 months in 9500 women, Oxford, United Kingdom (data from reference 23).
Table I. Some controlled trials of estrogen treatment for incontinence in postmenopausal women Type of incontinence Urge
Mixed Stress
Estrogen therapy Estradiol 2 mg + estriol 1 mg (placebo- controlled, double-blind, randomized) Estriol 3 mg (placebo- controlled, double-blind, randomized) Estriol 3 mg (design as above) Estriol 3 mg (design as above) Piperazine estrone sulfate 3 mg (placebo-controlled, doubleblind, randomized)
Route, duration, sample size
Efficacy
Oral, daily for 20 days per month for 4 months (n = 15) Oral, 3 months (n = 12)
Subjective improvement (less frequency, urgency, urge incontinence) Subjective improvement
Oral, 3 months (n = 8) Oral, 3 months (n = 11) Oral, 3 months (n = 18)
Subjective improvement No improvement Similar subjective improvement in both groups
(Table II). The incidence of urogenital symptoms such as vaginal dryness and decreasing libido in women who chose to consult a physician may be much higher compared with the prevalence of these symptoms as demonstrated in a large regional survey of British women (Fig. 2, upper two versus lower two lines). What is specific for women’s perceptions of urogenital symptoms? Many women have symptoms, sometimes to a severe degree, but are reluctant to seek professional help compared with other medical conditions. This may be because they do not realize that their symptoms can be successfully treated because symptoms are thought to be natural with advancing age or because the women are reluctant to discuss urogenital symptoms with often younger (male) physicians. The fear of causing embarrassment may be mutual because a taboo is attached to the issue. Appropriate information, including toll-free help lines offered by menopause societies, about the existence and variety of urogenital aging and potential modalities of cure are essential to be communicated not only to postmenopausal women but to the public in general. Well-known public figures may facilitate public
Authors Walter et al. (1978)7 Samsioe et al. (1985)8 Samsioe et al. (1985)8 Samsioe et al. (1985)8 Wilson et al. (1987)9
recognition of urogenital aging. Most current literature written to counsel women interested in the event of menopause concentrates on postmenopausal osteoporosis, cardiovascular disease, and vasomotor symptoms.24 Therefore short, easy-to-use checklists of potential urogenital symptoms as developed by medical societies such as The American College of Obstetricians and Gynecologists or the North American Menopause Society may encourage women to find access to diagnosis and treatment. Leaflets should be free of charge, easily available at primary health care centers and pharmacists, allow anonymous use, and provide communication assistance for women consulting a physician. Checklists provided by major pharmaceutical companies that take care of women’s health issues may be used as memory aid for physicians. Other relevant sources of information regarding treatment options for urogenital aging may be available through established patient associations such as osteoporosis self-help groups. Information will not only be useful for women but for their partners too because changes in the urogenital organs might be very distressing for a relationship unless adequate treatment is avail-
S256 Dören
May 1998 Am J Obstet Gynecol
Table II. Prevalence of urogenital symptoms
Sample size Age (yr) Prevalence (%) of symptoms Urinary incontinence Dysuria Recurrent UTI Urinary frequency Dyspareunia/dryness
Barlow et al. (1997)22 (Denmark, France, Germany, Italy, Netherlands, UnitedKingdom)
Iosif & Bekassy (1984)19 (Sweden)
Molander et al. (1990)18 (Sweden)
Oldenhave et al. (1993)20 (Netherlands)
van Geelen et al. (1996)21 (Netherlands)
1206 61
4206 65-84
5213 39-60
2159 50-75
3000 55-75
29
16.9
25 6
13
17.1 11.0†
25 25* 8 25
9
5.5 3.2 2.2 8.4 2.2
38
UTI, Urinary tract infection. *Combined percentage provided for discharge/pain + urinary incontinence + dysuria. †Combined percentage provided for pain, burning, pruritus, or vaginal discharge.
able and considered. The attitude of women in realizing that the changes of urogenital functions they might notice over time are symptoms for which treatment options may be asked is crucial for the recognition of urogenital disorders linked to estrogen deficiency. In conclusion, the message of contemporary health care for menopausal women with urogenital symptoms is to encourage a process of emancipation to enable these women and in general the public to understand, accept, and not suppress communication about the existence of these symptoms and ask for professional help of the medical community. Often simple approaches such as (local) estrogen replacement may significantly improve the quality of life. REFERENCES
1. von Schoultz B. Estrogens and urogenital epithelial function. Acta Obstet Gynecol Scand 1987;140(Suppl):28-32S. 2. Sarrel PM. Sexuality and menopause. Obstet Gynecol 1990;75:26-32S. 3. Bachmann GA. Vulvovaginal complaints. In: Lobo RA, editor. Treatment of the postmenopausal woman—basic and clinical aspects. New York: Raven Press; 1994. p. 137-42. 4. Nachtigall LE. Sexual function in the menopause and postmenopause. In: Lobo RA, editor. Treatment of the postmenopausal woman—basic and clinical aspects. New York: Raven Press; 1994. p. 301-6. 5. Fantl JA, Cardozo LA, McClish DK, Hormones and Urogenital Therapy Committee. Estrogen therapy in the management of urinary incontinence in postmenopausal women: a meta-analysis: first report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 1994;83:112-8. 6. Sultana CJ, Walters MD. Estrogen and urinary incontinence. Maturitas 1994;20:129-38. 7. Walter S, Wolf H, Barlebo H, Jensen HK. Urinary incontinence in postmenopausal women treated with estrogens: a doubleblind clinical trial. Urol Int 1978;33:135-43. 8. Samsioe G, Jansson I, Mellström D, Svanborg A. Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population. Maturitas 1985;7:335-42. 9. Wilson PD, Faragher B, Butler B, Bu’Lock D, Robinson EL, Brown ADG. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Gynaecol 1987;94:568-74.
10. Semmens J, Wagner G. Estrogen deprivation and vaginal function in postmenopausal women. JAMA 1982;248:445-8. 11. Mettler L, Olsen PG. Long-term treatment of atrophic vaginitis with low-dose estradiol vaginal tablets. Maturitas 1991;14 :23-31. 12. Eriksen PS, Rasmussen H. Low-dose 17β-oestradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol 1992;44:137-44. 13. Milsom I, Arvidsson L, Ekelund P, Molander U, Eriksson O. Factors influencing vaginal cytology, pH and bacterial flora in elderly women. Acta Obstet Gynecol Scand 1993;72:286-91. 14. Smith P, Heimer G, Lindskog M, Ulmsten U. Estradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. Maturitas 1993;16:145-54. 15. van der Linden MCGJ, Gerretsen G, Brandhorst MS, Ooms ECM, Kremer CME, Doesburg WH. The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms. Eur J Obstet Gynecol Reprod Biol 1993;51:29-33. 16. Utian WH, Schiff I. North American Menopause Society–Gallup survey on women’s knowledge, information sources, and attitudes to menopause replacement. Menopause 1994;1:39-48. 17. Rekers H, Drogendijk AC, Valkenburg HA, Riphagen F. The menopause, urinary incontinence and other symptoms of the genito-urinary tract. Maturitas 1992;15:101-11. 18. Molander U, Milsom I, Eklund P, Mellström D. An epidemiological study of urinary incontinence and related urogenital symptoms in elderly women. Maturitas 1990;12:51-60. 19. Iosif C, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand 1984;63:257-60. 20. Oldenhave A, Jaszman LJB, Haspels AA, Everaerd WTAM. Impact of climacteric on well-being: a survey based on 5213 women aged 39 to 60 years old. Am J Obstet Gynecol 1993;168:772-80. 21. van Geelen JM, van der Weijer PHM, Arnolds HT. Urogenital verschijnselen en hinder daarvan bij thuiswonende Nederlandse vrouwen van 50-75 jaar (Urogenital symptoms and resulting discomfort in non-institutionalized Dutch women aged 50 to 75 years). Ned Tijdschr Genesk 1996;140:713-6. 22. Barlow DH, Samsioe G, van Geelen JM. A study of European women’s experience of the problems of urogenital aging and its management. Maturitas 1997;27:239-47. 23. Barlow DH, Grosset KA, Hart H, Hart DM. A study of the experience of Glasgow women in the climacteric years. Br J Obstet Gynaecol 1991;302:274-6. 24. Millonig VL. Today and tomorrow’s woman. Menopause: before and after (girls of 16 to women of 99). Potomac: Health Leadership Associates; 1996.
Key words: Urogenital aging, estrogen deficiency, estrogen replacement therapy, women’s health
Menopause research is often associated with metric studies to assess, for example, the future fracture risk of postmenopausal osteoporosis or of major cardiovascular disease, to name only two examples. It is well known that symptoms of urgency, frequency, urinary incontinence, vaginal dryness, and related sexual problems develop in many menopausal women. The presentation of these symptoms is variable and often insidious; most often the symptoms tend to deteriorate with increasing age and may persist throughout life. This development over time suggests a relationship to menopausal estrogen deficiency.1-4 However, the distinctive role of estrogen deficiency in the pathogenesis of urogenital symptoms compared with that of the aging process per se is incompletely understood. Less research attention has been paid to lower urinary tract dysfunction and vaginal health in postmenopausal women as revealed by the selection of major topics of meetings dedicated to various areas of research on the menopause and basic and advanced medical training. Estrogen replacement therapy subjectively improves urinary incontinence5, 6 (Table I) and symptoms resulting from vaginal atrophy.10-15 However, more conclusive research data and in particular randomized, controlled long-term trials to substantiate benefits of estrogen treatment for urogenital health and in particular specific quality of life assessments are certainly welcome. The lack of this knowledge compared From the Department of Obstetrics and Gynecology, Westfälische Wilhelms–Universität Münster. Reprint requests: Martina Dören, MD, PhD, Universitäts-Frauenklinik Münster, Albert-Schweitzer-Str. 33, D-48129 Münster, Germany. Copyright © 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/0/88101
S254
with other areas of menopausal research is apparently linked to the insufficient awareness of the complex of urogenital aging even among physicians. Additional training to thus create awareness of health care providers for urogenital disorders should not only be offered to general practitioners, gynecologists, or urologists but start in medical schools as part of a women’s health teaching program. How relevant are disorders named urogenital aging? Feelings of vaginal discomfort, dyspareunia, and declining interest and activity in sex are complaints increasingly found in the period of the menopausal transition and thereafter. A telephone survey conducted in the United States revealed that one third of women aged 45 to 60 years complained of distressing changes in sexual function.16 According to epidemiologic studies, urinary incontinence and urinary tract infections are very common disorders in postmenopausal women17 and increase with age.18 One of the earliest—and largest—surveys conducted in elderly and very old women in Sweden clearly demonstrated that urinary incontinence and urinary tract infection are a most frequent complaint, thus an important medical problem (Fig. 1). Statistical figures generated in epidemiologic studies may need careful interpretation because the willingness and frequency to communicate the lack of urogenital well-being and related medical attention may be influenced by the cultural and social background of an individual postmenopausal woman. This latter aspect may help to explain why symptoms such as a decrease of libido and vaginal dryness are not necessarily frequently reported by a majority of perimenopausal and postmenopausal women as assessed in major epidemiologic surveys
Dören S255
Volume 178, Number 5 Am J Obstet Gynecol
Fig. 1. Postal survey in Gothenburg, Sweden, of 4206 women aged 65 to 85 years in 1979 (data from reference 18).
Fig. 2. Consultations for menopausal-postmenopausal symptoms over period of 6 months in 9500 women, Oxford, United Kingdom (data from reference 23).
Table I. Some controlled trials of estrogen treatment for incontinence in postmenopausal women Type of incontinence Urge
Mixed Stress
Estrogen therapy Estradiol 2 mg + estriol 1 mg (placebo- controlled, double-blind, randomized) Estriol 3 mg (placebo- controlled, double-blind, randomized) Estriol 3 mg (design as above) Estriol 3 mg (design as above) Piperazine estrone sulfate 3 mg (placebo-controlled, doubleblind, randomized)
Route, duration, sample size
Efficacy
Oral, daily for 20 days per month for 4 months (n = 15) Oral, 3 months (n = 12)
Subjective improvement (less frequency, urgency, urge incontinence) Subjective improvement
Oral, 3 months (n = 8) Oral, 3 months (n = 11) Oral, 3 months (n = 18)
Subjective improvement No improvement Similar subjective improvement in both groups
(Table II). The incidence of urogenital symptoms such as vaginal dryness and decreasing libido in women who chose to consult a physician may be much higher compared with the prevalence of these symptoms as demonstrated in a large regional survey of British women (Fig. 2, upper two versus lower two lines). What is specific for women’s perceptions of urogenital symptoms? Many women have symptoms, sometimes to a severe degree, but are reluctant to seek professional help compared with other medical conditions. This may be because they do not realize that their symptoms can be successfully treated because symptoms are thought to be natural with advancing age or because the women are reluctant to discuss urogenital symptoms with often younger (male) physicians. The fear of causing embarrassment may be mutual because a taboo is attached to the issue. Appropriate information, including toll-free help lines offered by menopause societies, about the existence and variety of urogenital aging and potential modalities of cure are essential to be communicated not only to postmenopausal women but to the public in general. Well-known public figures may facilitate public
Authors Walter et al. (1978)7 Samsioe et al. (1985)8 Samsioe et al. (1985)8 Samsioe et al. (1985)8 Wilson et al. (1987)9
recognition of urogenital aging. Most current literature written to counsel women interested in the event of menopause concentrates on postmenopausal osteoporosis, cardiovascular disease, and vasomotor symptoms.24 Therefore short, easy-to-use checklists of potential urogenital symptoms as developed by medical societies such as The American College of Obstetricians and Gynecologists or the North American Menopause Society may encourage women to find access to diagnosis and treatment. Leaflets should be free of charge, easily available at primary health care centers and pharmacists, allow anonymous use, and provide communication assistance for women consulting a physician. Checklists provided by major pharmaceutical companies that take care of women’s health issues may be used as memory aid for physicians. Other relevant sources of information regarding treatment options for urogenital aging may be available through established patient associations such as osteoporosis self-help groups. Information will not only be useful for women but for their partners too because changes in the urogenital organs might be very distressing for a relationship unless adequate treatment is avail-
S256 Dören
May 1998 Am J Obstet Gynecol
Table II. Prevalence of urogenital symptoms
Sample size Age (yr) Prevalence (%) of symptoms Urinary incontinence Dysuria Recurrent UTI Urinary frequency Dyspareunia/dryness
Barlow et al. (1997)22 (Denmark, France, Germany, Italy, Netherlands, UnitedKingdom)
Iosif & Bekassy (1984)19 (Sweden)
Molander et al. (1990)18 (Sweden)
Oldenhave et al. (1993)20 (Netherlands)
van Geelen et al. (1996)21 (Netherlands)
1206 61
4206 65-84
5213 39-60
2159 50-75
3000 55-75
29
16.9
25 6
13
17.1 11.0†
25 25* 8 25
9
5.5 3.2 2.2 8.4 2.2
38
UTI, Urinary tract infection. *Combined percentage provided for discharge/pain + urinary incontinence + dysuria. †Combined percentage provided for pain, burning, pruritus, or vaginal discharge.
able and considered. The attitude of women in realizing that the changes of urogenital functions they might notice over time are symptoms for which treatment options may be asked is crucial for the recognition of urogenital disorders linked to estrogen deficiency. In conclusion, the message of contemporary health care for menopausal women with urogenital symptoms is to encourage a process of emancipation to enable these women and in general the public to understand, accept, and not suppress communication about the existence of these symptoms and ask for professional help of the medical community. Often simple approaches such as (local) estrogen replacement may significantly improve the quality of life. REFERENCES
1. von Schoultz B. Estrogens and urogenital epithelial function. Acta Obstet Gynecol Scand 1987;140(Suppl):28-32S. 2. Sarrel PM. Sexuality and menopause. Obstet Gynecol 1990;75:26-32S. 3. Bachmann GA. Vulvovaginal complaints. In: Lobo RA, editor. Treatment of the postmenopausal woman—basic and clinical aspects. New York: Raven Press; 1994. p. 137-42. 4. Nachtigall LE. Sexual function in the menopause and postmenopause. In: Lobo RA, editor. Treatment of the postmenopausal woman—basic and clinical aspects. New York: Raven Press; 1994. p. 301-6. 5. Fantl JA, Cardozo LA, McClish DK, Hormones and Urogenital Therapy Committee. Estrogen therapy in the management of urinary incontinence in postmenopausal women: a meta-analysis: first report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 1994;83:112-8. 6. Sultana CJ, Walters MD. Estrogen and urinary incontinence. Maturitas 1994;20:129-38. 7. Walter S, Wolf H, Barlebo H, Jensen HK. Urinary incontinence in postmenopausal women treated with estrogens: a doubleblind clinical trial. Urol Int 1978;33:135-43. 8. Samsioe G, Jansson I, Mellström D, Svanborg A. Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population. Maturitas 1985;7:335-42. 9. Wilson PD, Faragher B, Butler B, Bu’Lock D, Robinson EL, Brown ADG. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Gynaecol 1987;94:568-74.
10. Semmens J, Wagner G. Estrogen deprivation and vaginal function in postmenopausal women. JAMA 1982;248:445-8. 11. Mettler L, Olsen PG. Long-term treatment of atrophic vaginitis with low-dose estradiol vaginal tablets. Maturitas 1991;14 :23-31. 12. Eriksen PS, Rasmussen H. Low-dose 17β-oestradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol 1992;44:137-44. 13. Milsom I, Arvidsson L, Ekelund P, Molander U, Eriksson O. Factors influencing vaginal cytology, pH and bacterial flora in elderly women. Acta Obstet Gynecol Scand 1993;72:286-91. 14. Smith P, Heimer G, Lindskog M, Ulmsten U. Estradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. Maturitas 1993;16:145-54. 15. van der Linden MCGJ, Gerretsen G, Brandhorst MS, Ooms ECM, Kremer CME, Doesburg WH. The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms. Eur J Obstet Gynecol Reprod Biol 1993;51:29-33. 16. Utian WH, Schiff I. North American Menopause Society–Gallup survey on women’s knowledge, information sources, and attitudes to menopause replacement. Menopause 1994;1:39-48. 17. Rekers H, Drogendijk AC, Valkenburg HA, Riphagen F. The menopause, urinary incontinence and other symptoms of the genito-urinary tract. Maturitas 1992;15:101-11. 18. Molander U, Milsom I, Eklund P, Mellström D. An epidemiological study of urinary incontinence and related urogenital symptoms in elderly women. Maturitas 1990;12:51-60. 19. Iosif C, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand 1984;63:257-60. 20. Oldenhave A, Jaszman LJB, Haspels AA, Everaerd WTAM. Impact of climacteric on well-being: a survey based on 5213 women aged 39 to 60 years old. Am J Obstet Gynecol 1993;168:772-80. 21. van Geelen JM, van der Weijer PHM, Arnolds HT. Urogenital verschijnselen en hinder daarvan bij thuiswonende Nederlandse vrouwen van 50-75 jaar (Urogenital symptoms and resulting discomfort in non-institutionalized Dutch women aged 50 to 75 years). Ned Tijdschr Genesk 1996;140:713-6. 22. Barlow DH, Samsioe G, van Geelen JM. A study of European women’s experience of the problems of urogenital aging and its management. Maturitas 1997;27:239-47. 23. Barlow DH, Grosset KA, Hart H, Hart DM. A study of the experience of Glasgow women in the climacteric years. Br J Obstet Gynaecol 1991;302:274-6. 24. Millonig VL. Today and tomorrow’s woman. Menopause: before and after (girls of 16 to women of 99). Potomac: Health Leadership Associates; 1996.