Urogenital Atrophy: Prevention and Treatment
Dr. Laurie A. Willhite Pharm.D.,
Dr. Mary Beth O'Connell Pharm.D., FASHP, FCCP,
Dr. Laurie A. Willhite Pharm.D.
Pharmacy Department, Fairview University Medical Center
College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
Search for more papers by this authorCorresponding Author
Dr. Mary Beth O'Connell Pharm.D., FASHP, FCCP
Experimental and Clinical Pharmacology Department, University of Minnesota, Minneapolis, Minnesota
University of Minnesota, College of Pharmacy, Experimental and Clinical Pharmacology Department, WDH 9-157, 308 Harvard Street SE, Minneapolis, MN 55455-0353Search for more papers by this authorDr. Laurie A. Willhite Pharm.D.,
Dr. Mary Beth O'Connell Pharm.D., FASHP, FCCP,
Dr. Laurie A. Willhite Pharm.D.
Pharmacy Department, Fairview University Medical Center
College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
Search for more papers by this authorCorresponding Author
Dr. Mary Beth O'Connell Pharm.D., FASHP, FCCP
Experimental and Clinical Pharmacology Department, University of Minnesota, Minneapolis, Minnesota
University of Minnesota, College of Pharmacy, Experimental and Clinical Pharmacology Department, WDH 9-157, 308 Harvard Street SE, Minneapolis, MN 55455-0353Search for more papers by this authorAbstract
Fifteen percent of premenopausal women, 10–40% of postmenopausal women, and 10–25% of women receiving systemic hormone therapy experience urogenital atrophy. The most common symptoms are dryness, burning, pruritus, irritation, and dyspareunia. Estrogen loss, drugs, and chemical sensitivities are causes. Estrogen or hormone replacement therapy (ERT-HRT) is the treatment of choice in postmenopausal women. Dosages prescribed for menopause symptoms or to prevent osteoporosis (and, potentially, other conditions) can restore the vagina to premenopausal physiology and relieve symptoms. Concomitant progestins are necessary for women with an intact uterus to minimize or eliminate estrogen-induced endometrial cancer. Low-dosage oral and vaginal ERT can relieve urogenital atrophy but might not produce systemic effects. Progestins are not necessary with vaginal rings and vaginal tablets. If ERT is given only to treat urogenital atrophy, estrogen creams 1 or 2 times/week may prevent recurrence after symptoms are resolved. Progestins are not required for occasional estrogen cream use. Vaginal moisturizers provide longer relief by changing the fluid content of endothelium and lowering vaginal pH. Vaginal lubricants provide short-term relief. Women with contraindications to ERT-HRT could use lubricants for intercourse-related dryness or moisturizers for more continuous relief. The lay press promotes agrimony, black cohosh, chaste tree, dong quai, witch hazel, and phytoestrogens for vaginal dryness and dyspareunia; however, no evidence exists to support these specific claims. Pharmacists should be actively involved in identifying, preventing, and treating urogenital atrophy.
References
- 1 Notelovitz M. Urogenital atrophy and low-dose vaginal estrogen therapy [editorial]. Menopause 2000; 7: 140–2.
- 2 Bachmann G.A., Nevadunsky N.S. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician 2000; 61: 3090–6.
- 3 Debrovner D. The new VD. Am Druggist 1993; 18: 39–43.
- 4 Krantz K.E. The human vagina. Clin Pract Sex 1990; 8(suppl): 4–10.
- 5 Semmens J.P. Vaginal physiology. Clin Pract Sex 1990; 8(suppl): 2–3.
- 6 Pandit L., Ouslander J.G. Postmenopausal vaginal atrophy and atrophic vaginitis. Am J Med Sci 1997; 314: 228–31.
- 7 Hillier S.L., Lau R.J. Vaginal microflora in postmenopausal women who have not received estrogen replacement therapy. Clin Infect Dis 1997; 25(suppl 2: S123–6.
- 8 Hodgins M.B., Spike R.C., Mackie R.M., MacLean A.B. An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol 1998; 105: 216–22.
- 9 Sarrel P.M. Ovarian hormones and vaginal blood flow: using laser Doppler velocimetry to measure effects in a clinical trial of post-menopausal women. Int J Impot Res. 1998; 10(suppl 2: S91–3.
- 10 Rigg L.A. Estrogen replacement therapy for atrophic vaginitis. Int J Fertil 1986; 31(suppl 3: 29–34.
- 11 Foster D.C., Palmer M., Marks J. Effect of vulvovaginal estrogen on sensorimotor response of the lower genital tract: a randomized controlled trial. Obstet Gynecol 1999; 94: 232–7.
- 12 O'Connell M.B. Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol 1995; 35: 18S–24.
- 13 Elia G., Bergman A. Estrogen effects on the urethra: beneficial effects in women with genuine stress incontinence. Obstet Gynecol Surv 1993; 48: 509–17.
- 14 Capwell A.E., McIntyre M.A., Elton R.A. Postmenopausal atrophy in elderly women: is a vaginal smear necessary for diagnosis? Age Aging 1992; 21: 117–20.
- 15 Wisniewski P.M., Wilkinson E.J. Postpartum vaginal atrophy. Am J Obstet Gynecol 1991; 165: 1249–54.
- 16 Goetsch M.F. Postpartum dyspareunia, an unexplored problem. J Reprod Med 1999; 44: 963–8.
- 17 Leiblum S., Bachmann G.A., Kemmann E., Colburn D., Swartzman L. Vaginal atrophy and the postmenopausal woman: the importance of sexual activity and hormones. JAMA 1983; 249: 2195–8.
- 18 Lilly Research Laboratories. Raloxifene (Evista) data on file. Indianapolis, IN; January 2000.
- 19 Cohen F., Watts S., Beymer K. Vaginal complaints in healthy postmenopausal women: data from a 3-year trial comparing raloxifene with conjugated estrogens or placebo [abstr]. Presented at the 9th annual meeting of the North American Menopause Society, Toronto, Canada, August 1619, 1998.
- 20 Kalogeraki A., Tamiolakis D., Relakis K., et al. Cigarette smoking and vaginal atrophy in postmenopausal women. In Vivo 1996; 10: 597–600.
- 21 Channon L.D., Ballinger S.E. Some aspects of sexuality and vaginal symptoms during menopause and their relation to anxiety and depression. Br J Med Psychol 1986; 59(part 2): 173–80.
- 22 Semmens J.P., Wagner G. Estrogen deprivation and vaginal function in postmenopausal women. JAMA 1982; 248: 445–8.
- 23 Geola F.L., Frumar A.M., Tataryn I.V., et al. Biological effects of various doses of conjugated equine estrogens in postmenopausal women. J Clin Endocrinol Metab 1980; 51: 620–5.
- 24 Semmens J.P., Tsai C.C., Semmens E.C., Loadholt C.B. Effects of estrogen therapy on vaginal physiology during menopause. Obstet Gynecol 1985; 66: 15–18.
- 25 Wren B.G., Brown L.B., Routledge D.A. Differential clinical response to estrogens after menopause. Med J Aust 1982; 2: 329–32.
- 26 van der Linden MCGJ, Gerretsen G., Brandhorst M.S., Ooms E.C.M., Kremer C.M.E., Doesburg W.H. 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.
- 27 Brandberg A., Mellstrom D., Samsioe G. Low dose oral estriol treatment in elderly women with urogenital infections. Acta Obstet Gynecol Scand 1987; 140(suppl): 33–8.
- 28 Chetkowski R.J., Meldrum D.R., Steingold K.A., et al. Biologic effects of transdermal estradiol. N Engl J Med 1986; 314: 1615–20.
- 29 Bellantoni M.F., Harman S.M., Cullins V.E., Engelhardt S.M., Blackman M.R. Transdermal estradiol with oral progestin: biological and clinical effects in younger and older postmenopausal women. J Gerontol 1991; 46: M216–22.
- 30 Nilsson K.E., Heimer G.M. Ultra-low-dose transdermal estrogen therapy in postmenopausal urogenital estrogen deficiency—a placebo-controlled study. Menopause 1994; 1: 191–7.
- 31 Martin P.L., Yen S.S.C., Burnier A.M., Hermann H. Systemic absorption and sustained effects of vaginal estrogen creams. JAMA 1979; 42: 2699–700.
- 32 Dickerson J., Bressler R., Christian C.D., Hermann H.W. Efficacy of estradiol vaginal cream in postmenopausal women. Clin Pharmacol Ther 1979; 26: 502–7.
- 33 Mandel F.P., Geola F.L., Meldrum D.R., et al. Biological effects of various doses of vaginally administered conjugated equine estrogens in postmenopausal women. J Clin Endocrinol Metab 1983; 57: 133–9.
- 34 Handa V.L., Bachus K.E., Johnston W.W., Robboy S.J., Hammond C.B. Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium. Obstet Gynecol 1994; 84: 215–28.
- 35 Luisi M., Franchi F., Kicovic P.M. A group-comparative study of effects of Ovestin cream versus Premarin cream in post-menopausal women with vaginal atrophy. Maturitas 1980; 2: 311–39.
- 36 Kicovic P.M., Cortes-Prieto J., Milojevic S., Haspels A.A., Aljinovic A. The treatment of postmenopausal vaginal atrophy with Ovestin vaginal cream or suppositories: clinical, endocrinological and safety aspects. Maturitas 1980; 2: 275–82.
- 37 Ayton R.A., Darling G.M., Murkies A.L., et al. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Br J Obstet Gynaecol 1996; 103: 351–8.
- 38 Notelovitz M. Estrogen therapy in the management of problems associated with urogenital ageing: a simple diagnostic test and the effect of the route of hormone administration. Maturitas 1995; 22(suppl): S31–3.
- 39 Chompootaweep S., Nunthapisud P., Trivijitsilp P., Sentrakul P., Dusitsin N. The use of two estrogen preparations (a combined contraceptive pill versus conjugated estrogen cream) intravaginally to treat urogenital symptoms in postmenopausal Thai women: a comparative study. Clin Pharmacol Ther 1998; 64: 204–10.
- 40 Gordon W.E., Herman H.W., Hunter D.C. Safety and efficacy of micronized estradiol vaginal cream. South Med J 1979; 72: 1252–8.
- 41 Bygdeman M., Swahn M.L. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas 1996; 23: 259–63.
- 42 Mattson L.A., Cullberg G. A clinical evaluation of treatment with estriol vaginal cream versus suppository in postmenopausal women. Acta Obstet Gynecol Scand 1983; 62: 397–401.
- 43 Barentsen, R., van de Weijer P.H.M., Schram J.H.N. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. Eur J Obstet Gynecol Reprod Biol 1997; 71: 73–80.
- 44 Raz R., Stamm W.E. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993; 329: 753–6.
- 45 Nilsson K., Risberg B., Heimer G. The vaginal epithelium in the postmenopause—cytology, histology and pH as methods of assessment. Maturitas 1995; 21: 51–6.
- 46 Nilsson K., Heimer G. Low-dose oestradiol in the treatment of urogenital oestrogen deficiency—a pharmacokinetic and pharmacodynamic study. Maturitas 1992; 15: 121–7.
- 47 Smith P., Heimer G., Lindskog M., Ulmsten U. Oestradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. Maturitas 1993; 16: 145–54.
- 48 Eriksen B.C. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol 1999; 180: 1072–9.
- 49 Henriksson L., Stjernquist M., Boquist L., Cedergren I., Selinus I. A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Am J Obstet Gynecol 1996; 174: 85–92.
- 50 Henriksson L., Stjernquist M., Boquist L., Alander U., Selinus I. A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. Am J Obstet Gynecol 1994; 171: 624–32.
- 51 Pschera H., Hjerpe A., Carlstrom K. Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17 beta and progesterone in postmenopausal women. Gynecol Obstet Invest 1989; 27: 204–7.
- 52 Furuhjelm M., Karlgren E., Carlstrom K. Intravaginal administration of conjugated estrogens in premenopausal and postmenopausal women. Int J Gynaecol Obstet 1980; 17: 335–9.
- 53 Nilsson K., Heimer G. Low-dose 17β-oestradiol during maintenance therapy—a pharmacokinetic and pharmacodynamic study. Maturitas 1995; 21: 33–8.
- 54 Mettler L., Olsen P.G. Long-term treatment of atrophic vaginitis with low-dose estradiol vaginal tablets. Maturitas 1991; 14: 23–31.
- 55 Eriksen P.S., Rasmussen H. Low-dose 17β-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol 1992; 44: 137–44.
- 56 Rioux J.E., Devlin M.C., Gelfand M.M., Steinberg W.M., Hepburn D.S. 17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 2000; 7: 156–61.
- 57 Dugal R., Hesla K., Sordal T., Aase K.H., Lilleeidet O., Wickstrom E. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand 2000; 79: 283–7.
- 58 Lose G. Oestradiol-releasing vaginal rings versus estriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. Br J Obstet Gynaecol 2000; 107: 1029–34.
- 59 Iosif C.F. Effects of protracted administration of estriol on the lower genitourinary tract in postmenopausal women. Arch Gynecol Obstet 1992; 251: 115–20.
- 60 Grady D., Rubin S.M., Petitti D.B., et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Int Med 1992; 117: 1016–37.
- 61 Cardoza L., Bachmann G., McClish D., Fonda D., Birgerson L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the hormones and urogenital therapy committee. Obstet Gynecol 1998; 92: 722–7.
- 62 Aventis Pharmaceuticals. Combipatch data on file. King of Prussia, PA; March 29 2000.
- 63 Carlstrom K., Karlgren E., Furuhjelm M., Ryd-Kjellen E. Effects of intravaginal oestrogen treatment upon the vaginal absorption of conjugated equine oestrogens. Maturitas 1982; 4: 277–83.
- 64 Keenan N.L., Franks A.L., Croft J.B., Scholes D., Murray E.T. Vaginal estrogen creams: use patterns among a cohort of women. J Am Geriatr Soc 1999; 47: 65–70.
- 65 Englund D.E., Johansson E.D.B. Plasma levels of oestrone, oestradiol, and gonadotropins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin). Br J Obstet Gynaecol 1978; 85: 957–64.
- 66 Tourgeman D.E., Gentzchein E., Stanczyk F.Z., Paulson R.J. Serum and tissue hormone levels of vaginally and orally administered estradiol. Am J Obstet Gynecol 1999; 180: 1480–3.
- 67 Ruggiero R.J. Gynecologic disorders. In: E.T. Herfindel, D.R. Gourley, eds. Textbook of therapeutics, drug and disease management. Baltimore: Williams & Wilkins, 1996: 1721–39.
- 68 Wyeth-Ayerst. Premarin cream package insert. Princeton, NJ; May 5, 1998.
- 69 Pitkin R.M., VanVoorhis L.W. Postirradiation vaginitis: an evaluation of prophylaxis with topical estrogen. Radiology 1971; 99: 417–21.
- 70 Abitbol M.M., Davenport J.H. The irradiated vagina. Obstet Gynecol 1974; 44: 249–56.
- 71 Schmidt G., Andersson S.B., Nordle O., Johansson C.J., Gunnarsson P.O. Release of 17-beta-oestradiol from a vaginal ring in postmenopausal women: pharmacokinetic evaluation. Gynecol Obstet Invest 1994; 38: 253–60.
- 72 Cohen F.J., Watts S., Shah A., Akers R., Plouffe L. Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60. Obstet Gynecol 2000; 95: 104–10.
- 73 Rymer J., Chapman M.G., Fogelman I., Wilson P.O.G. A study of the effect of tibolone on the vagina in postmenopausal women. Maturitas 1994; 18: 127–33.
- 74 Botis D., Kassanos D., Kalogirou D., Antoniou G., Vitoratos N., Karakitsos P. Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: a comparison. Maturitas 1997; 26: 57–62.
- 75 Frishman G.N., Luciano A.A., Maier D.B. Evaluation of Astroglide, a new vaginal lubricant: effects of length of exposure and concentration and sperm motility. Fertil Steril 1992; 58: 630–2.
- 76 Kutteh W.H., Caho C.H., Ritter J.O., Byrd W. Vaginal lubricants for the infertile couple: effect on sperm activity. Int J Fertil 1996; 41: 400–4.
- 77 Anderson L., Lewis S.E.M., McClure N. The effects of coital lubricants on sperm motility in vitro. Hum Reprod 1998; 13: 3351–6.
- 78 Goldenberg R.L., White R. The effect of vaginal lubricants on sperm motility in vitro. Fertil Steril 1975; 26: 872–3.
- 79 Tulandi T., McInness R.A. Vaginal lubricants: effect of glycerin and egg white on sperm motility and progression in vitro. Fertil Steril 1984; 41: 151–3.
- 80 Upsher-Smith Laboratories, Inc.. Lubrin data on file. Minneapolis, MN; 1988.
- 81 Rosen A.D., Rosen T. Study of condom integrity after brief exposure to over-the-counter vaginal preparations. South Med J 1999; 92: 305–7.
- 82 Smith A.M.A., Jolley D., Hocking J., Benton K., Gerofi J. Does additional lubrication affect condom slippage and breakage? Int J STD AIDS 1998; 9: 330–5.
- 83 Bachmann G.A., Notelovitz M., Gonzalez S.J., Thompson C., Morecraft B.A. Vaginal dryness in the menopausal woman: clinical characteristics and non hormonal treatment. Clin Pract Sex 1991; 7: 1–8.
- 84 Brown J., Hooper G., Kenyon C.J., et al. Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy. Pharm Res. 1997; 14: 1073–8.
- 85 Nachtigall L.E. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril 1994; 61: 178–80.
- 86 Sato R., Sugiuchi A., Hiroi M., Nakamura R.M. A nonhormonal bioadhesive vaginal moisturizer. II. Effects on condom strength. Clin Pract Sex 1992; 8: 4–5.
- 87 Sato R., Sugiuchi A., Hiroi M., Nakamura R.M. A nonhormonal bioadhesive vaginal moisturizer. I. Effect on sperm motility and ova penetration. Clin Pract Sex 1992; 8: 1–3.
- 88 Loprinzi C.L., Abu-Ghazaleh S., Sloan J.A., et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol 1997; 15: 969–73.
- 89 Speroff L. Facts and fallacies: “natural” alternatives for menopause? Contemp Obstet Gynecol 1999;Feb(suppl): 4–24.
- 90 Israel D., Youngkin E.Q. Herbal therapies for perimenopausal and menopausal complaints. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 1997; 17: 970–84.
- 91 Foster S. Black cohosh (Cimicifuga racemosa): a literature review. Herbalgram 1999; 45: 35–49.
- 92 Liske E., Wustenberg P. Therapy of climacteric complaints with Cimicifuga racemosa: herbal medicine with clinically proven evidence [abstr]. Maturitas 1998; 5: 250.
- 93 Foster S., Tyler V.E. Tyler's honest herbal: a sensible guide to the use of herbs and related remedies, 4th ed. Binghamton, NY: Haworth Press, 1998.
- 94 Hirata J.D., Swiersz L.M., Zell B., Small R., Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997; 68: 981–6.
- 95 Albertazzi P., Pansini F., Bottazzi M., Bonaccorsi G., De Aloysio D., Morton M.S. Dietary soy supplementation and phytoestrogen levels. Obstet Gynecol 1999; 94: 229–31.
- 96 Washburn S., Burke G.L., Morgan T., Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999; 6: 7–13.
Citing Literature
