A Systematic Review of Atrophic Vaginitis Treatment, Duration of Therapy, and Healthcare Costs Sanjeev Balu, PhD1; Ashish V. Joshi, MS, PhD2; David Cobden, MSc, MPH2; Won Chan Lee, PhD1; Chris L. Pashos, PhD1 1HERQuLES, Abt Associates Inc., Bethesda, MD, USA; 2Novo Nordisk Inc., Princeton, NJ, USA KEY FINDINGS Abstract Table 1: Duration of Hormonal Therapy
• Studies have shown that AV is a common problem occurring in
OBJECTIVES: A systematic review of the prevalence of atrophic
• A systematic literature search (1990 to 2005) was performed to
postmenopausal women.1-4 More specifically, AV can occur in 10%-
vaginitis, treatments involved, therapy duration, and associated
identify articles with qualitative and quantitative data on AV
40% of postmenopausal women, up to 15% of pre-menopausal
Duration of Objective Outcome Measures
healthcare costs was undertaken to identify studies with clinical and
treatments, treatment duration, and the economic impact of
women, and 10%-25% of women on systemic hormone therapy.5
Weisberg E, et al. 2005
economic relevance and gaps in literature.
• Patients with AV tend to be under-diagnosed. Less than 25%
METHODS: A systematic literature search using an exhaustive list
• Electronic MEDLINE®/PubMed® searches along with manual review
discuss the condition with their healthcare providers or try to seek
Palacios S, et al. 2005
of relevant search terms (1990-2004) was performed to identify
articles with qualitative and quantitative data on atrophic vaginitis
• A comprehensive list of key search words was used, including,
• Hormone replacement therapy (HRT) is the most common
Raymundo N, et al. 2004
treatments, treatment duration, and economic impact of treatment
treatment for AV since decreased estrogen level is a major risk
duration. Electronic Medline® and PubMed® searches along with
- “atrophic vaginitis”, “urogenital atrophy”, “vaginitis” AND
manual review of bibliographies were conducted in different phases
“epidemiology”, “prevalence”, “incidence”, “compliance”,
• Vaginal estrogen preparations have been shown to be more
Marx P, et al. 2004
“costs”, “economics”, “cost-sharing”, and “co-payments”
efficacious and easier to use than systemic estrogen
RESULTS: Out of 35 retrieved studies, 6 were on epidemiology, 14
• All search terms were limited to Medical Subjects Headings
on treatment patterns, 8 on treatment duration, and 7 studies
[MESH] terms, English–language abstracts, human subjects, and
- Advantages of locally administered estrogen preparations
Akrivis Ch, et al. 2003
showed comparisons between vaginal tablets and other vaginal
Evaluate the clinical efficacy and safety
year 1990 to 2005, except for the articles on epidemiology which
over systemic preparations include: 1) convenience and
preparations. Overall, studies examining prevalence showed that
were limited from year 2000 to 2005.
avoidance of systemic adverse effects; 2) prevention of
atrophic vaginitis was commonly occurring among postmenopausal
hepatic metabolism and increased response of vaginal
Notelovitz M, et al. 2002
• We supplemented our search with several additional resources
women (10-40%), and affecting as many as 15% of pre-meno-
tissues to locally applied estrogen; 3) rapid and efficient
including E-medicine® and internet searches
pausal women and 10-25% of women on systemic hormone therapy.
absorption into the systemic circulation through vaginal
Diagnosis of this condition was low with less than 25% discussing
Rioux JE, et al. 2000
the condition with their healthcare providers and only 20-25%
• The overall duration of treatment for atrophic vaginitis ranges
seeking medical attention. Treatment duration was found to be in
from 2 to 12 months (weighted average of 4.1 months).10-17
the range of 2-12 months (weighted average of 4.1 months).
Studies on long-term safety and efficacy of treatment are lacking. SEARCH RESULTS
• Clinical trials have evaluated safety and efficacy outcomes,
Vaginal tablets were preferred over vaginal creams due to conve-
Dugal R, et al. 2000
• Of 235 possible publications identified electronically, 27 were
including cytological changes and changes in pH.10-17
deemed appropriate for analysis. The distribution of these clinical
• The major side effect of HRT is increased systemic estrogen
CONCLUSIONS: No data exist that mirror treatment duration in a
concentrations. Some of the above clinical trials showed that
“real-world” setting. There is a complete lack of studies correlating
• A manual review of bibliographies yielded 8 more unique articles
vaginal estrogen preparations, especially the low-dose vaginal
treatment duration with overall healthcare costs both at an indi-
tablets, resulted in low absorption of estrogen without the
vidual and national level. Health economic studies examining
systemic effects often associated with HRT.11,15,16 Also, vaginal
resource utilization patterns, cost drivers and economic burden of
• Overall, 35 relevant studies were identified and analyzed in the
tablets were found to be a better alternative to other local
this condition on individuals and society at large were not found.
estrogen preparations due to higher safety and better conve-
Future research needs to examine relationships between treatment
- Of these 35 studies, 6 (17%) were epidemiological, 22
duration, choice of medication, adherence, incidence of adverse
(63%) were on treatment patterns or treatment duration,
• AV is typically under-diagnosed and those diagnosed
• However, no studies were identified that quantify levels of
with AV rarely seek treatment.
and 7 studies (20%) compared vaginal tablets and other
adherence (i.e., treatment duration and treatment intensity) to
current treatment regimens in a “real world” setting.
• Economic/outcome studies of patients with AV are Introduction lacking in the literature, and no studies pertainng to Figure 1: Distribution of Retrieved Articles Based
• Health economic studies examining resource utilization patterns,
medication adherance were found.
• Vaginitis is an inflammation of the vagina that can cause dis-
cost drivers and economic burden of this condition on individuals
on Study Methods
• Future studies need to examine the associations between
charge, itching, or pain. The most common types of vaginitis are
and society at large were not found. treatment duration, medication adherence, and economic
bacterial vaginitis, yeast infections, trichomoniasis, and atrophic
• Studies on long-term safety and efficacy of AV treatment are also
• AV, also known as urogenital atrophy, is inflammation of the
vagina due to thinning and shrinking tissues and decreased
lubrication of the vaginal walls caused by a lack of estrogen
National Library of Medicine. Medical encyclopedia: atrophic vaginitis. Available at: http://
• Successful management of AV depends, in part, on patient
• Despite the high prevalence of AV, vaginal estrogen therapy
www.nlm.nih.gov/medlineplus/ency/article/000892.htm. Accessed 5/8/06.
Nothnagle M, Taylor S. Vaginal estrogen preparations for relief of atrophic vaginitis. Am Fam Physician.
(VET) was underutilized. The magnitude of this underutilization of
Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician.
treatment should be investigated in the future.
• Better adherence is associated with symptom alleviation and
Willhite LA, et al. Urogenital atrophy: prevention and treatment. Pharmacotherapy. 2001;21(4):464-480.
Notelovitz M. Urogenital atrophy and low-dose vaginal estrogen therapy (editorial). Menopause.
• Convenience and the mode of administration are perceived key
Bachmann GA. Influence of menopause on sexuality. Int J Fertil. 1995;40:16-22.
• Little is known about the extent to which “real world” patients
advantages of vaginal tablets compared with other local dosage
Berman JR, Goldstein I. Female sexual dysfunction. Urol Clin N Am. 2001;28:405-416.
Freedman MA. Quality of life and menopause: the role of estrogen. J Womens Health. 2002;11:703-718.
with AV adhere to current available treatment regimens.
forms (e.g., vaginal creams). In light of the hypothesis that these
Bellantoni MF, et al. Transdermal estradiol with oral progestin: biological and clinical effects in younger and
advantages are likely to increase patient adherence to treatment
older postmenopausal women. J Gerontol. 1991;46:M216-222.
Weisberg E, et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal
tablet. Climacteric. 2005;8:83-92. OBJECTIVES
regimens, thereby resulting in improved clinical outcomes, the
Palacios S, et al. Low-dose, vaginally administered estrogens may enhance local benefits of systemic
therapy in the treatment of urogenital atrophy in postmenopausal women on hormone therapy. Maturitas.
1) To describe levels of adherence and their relationship with
level of adherence (i.e., treatment duration and intensity of
Raymundo N, et al. Treatment of atrophic vaginitis with topical conjugated equine estrogens in
treatment duration with healthcare resource utilization and
medication use) of vaginal tablets compared to other local
postmenopausal Asian women. Climacteric. 2004;7(3):312-318.
Marx P, et al. Low-dose (0.3 mg) synthetic conjugated estrogens A is effective for managing atrophic
vaginitis. Maturitas. 2004;47(1):47-54.
Akrivis Ch, et al. Action of 25 microg 17beta-oestradiol vaginal tablets in the treatment of vaginal atrophy
2) To synthesize measurements of treatment duration observed in
• Because AV is not a chronic medical condition, appropriate
in Greek postmenopausal women; clinical study. Clin Exp Obstet Gynecol. 2003;30(4):229-234.
Notelovitz M, et al. Estradiol absorption from vaginal tablets in postmenopausal women. Obstet Gynecol.Presented at the 11th Annual ISPOR Meeting
measures of adherence should be carefully selected.
Rioux JE, et al. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve
3) To identify adherence-related issues and directions for future
May 20-24, 2006; Philadelphia, PA
menopausal atrophic vaginitis. Menopause. 2000;7(3):140-142
Dugal R, et al. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of
vaginal atrophy. Acta Obstet Gynecol Scand. 2000;79(4):293-297.
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Manual therapies for migraine: a systematic reviewAleksander Chaibi • Peter J. Tuchin •Michael Bjørn RussellReceived: 4 November 2010 / Accepted: 14 January 2011 / Published online: 5 February 2011Ó The Author(s) 2011. This article is published with open access at Springerlink.comMigraine occurs in about 15% of the generaldue to side effects, or contraindications due to co-morbiditypopu