Suckling J, Lethaby A, Kennedy R.
Local oestrogen for vaginal atrophy in postmenopausal women.
Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. doi: 10.1002/14651858.CD001500.pub2. Epub 2006 Oct 18.
Abstract/Text
BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring).
OBJECTIVES: The objective of this review was to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy.
SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Register of trials (searched January 2006), The Cochrane Library (2006,Issue 2), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), Current Contents (1993 to January 2006, Biological Abstracts (1969 to 2006), Social Sciences Index (1980 to January 2006), PsycINFO (1972 to February 2006), CINAHL (1982 to January 2006) and reference list of articles. We also contacted manufacturers and researchers in the field.
SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis.
DATA COLLECTION AND ANALYSIS: Thirty-seven trials were identified: of these 18 were excluded. Included trials were assessed for quality and two reviewer authors extracted data independently. The ratios for dichotomous outcomes and means for continuous outcomes were calculated. The outcomes analysed were categorised under the headings of: efficacy, safety and acceptability.
MAIN RESULTS: Nineteen trials with 4162 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy, with various outcome measures. When comparing the efficacy of different oestrogenic preparations (in the form of creams, pessaries, tablets and the oestradiol-releasing vaginal ring) in relieving the symptoms of vaginal atrophy, results indicated significant findings favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and seven looked at adverse effects. One trial showed significant adverse effects of the cream (conjugated equine oestrogen) when compared to tablets (oestradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by a progestagen challenge test with the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to the cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (oestradiol). Eleven studies compared acceptability to the participants by comparing: comfort of product use, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the oestradiol-releasing vaginal ring.
AUTHORS' CONCLUSIONS: Creams, pessaries, tablets and the oestradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following use of the cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the oestradiol-releasing vaginal ring for ease of use, comfort of product and overall satisfaction.
日本産科婦人科学会・日本産婦人科医会：産婦人科診療ガイドライン-婦人科外来編2023、日本産科婦人科学会、2023.
Cardozo 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 Oct;92(4 Pt 2):722-7. doi: 10.1016/s0029-7844(98)00175-6.
Abstract/Text
OBJECTIVE: To evaluate the efficacy of estrogen therapy in the treatment of postmenopausal women with symptoms and signs associated with urogenital atrophy, by meta-analysis of available data.
METHODS: We searched the literature (Excerpta Medica, Biosis, MEDLINE, and hand search) for studies published between January 1969 and April 1995. Criteria for inclusion were English-language articles, peer-reviewed original publications, and urogenital atrophy assessed by at least one of the following outcomes: patient symptoms, physician report, pH, or cytologic change. Data had to allow comparison between treated and control groups in controlled trials or an estimated change from baseline in uncontrolled series. Meta-analytic methods were applied separately to controlled clinical trials and uncontrolled studies.
RESULTS: Of the 77 relevant articles reviewed, nine contained ten randomized controlled trials. Meta-analysis of these using the Stouffer method revealed a statistically significant benefit of estrogen therapy for all outcomes studied. In 54 uncontrolled case series, the patient symptoms were treated by 24 different treatment modalities. All routes of administration appeared to be effective and maximum benefit was obtained between 1 and 3 months after the start of treatment. As expected, the least systemic absorption of estrogen was seen with estriol (administered orally or vaginally), then vaginal estradiol as measured by pretherapy and posttherapy serum estradiol and estrone.
CONCLUSION: Estrogen is efficacious in the treatment of urogenital atrophy and low-dose vaginal estradiol preparations are as effective as systemic estrogen therapy in the treatment of urogenital atrophy in postmenopausal women.
Raz R, Stamm WE.
A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.
N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.
Abstract/Text
BACKGROUND: Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections.
METHODS: We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up.
RESULTS: The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment.
CONCLUSIONS: The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.
North American Menopause Society.
The 2012 hormone therapy position statement of: The North American Menopause Society.
Menopause. 2012 Mar;19(3):257-71. doi: 10.1097/gme.0b013e31824b970a.
Abstract/Text
OBJECTIVE: This position statement aimed to update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2010 regarding recommendations for hormone therapy (HT) for postmenopausal women. This updated position statement further distinguishes the emerging differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) at various ages and time intervals since menopause onset.
METHODS: An Advisory Panel of expert clinicians and researchers in the field of women's health was enlisted to review the 2010 NAMS position statement, evaluate new evidence, and reach consensus on recommendations. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement.
RESULTS: Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women's health and recognizes the greater safety profile associated with ET.
CONCLUSIONS: Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture. The more favorable benefit-risk ratio for ET allows more flexibility in extending the duration of use compared with EPT, where the earlier appearance of increased breast cancer risk precludes a recommendation for use beyond 3 to 5 years.
日本産科婦人科学会・日本女性医学学会（監修）：ホルモン補充療法ガイドライン2017年度版、日本産科婦人科学会、2017.
Society of Obstetricians and Gynaecologists of Canada.
SOGC clinical practice guidelines. The detection and management of vaginal atrophy. Number 145, May 2004.
Int J Gynaecol Obstet. 2005 Feb;88(2):222-8. doi: 10.1016/j.ijgo.2004.11.003.
Abstract/Text
OBJECTIVE: To support the practitioner in the diagnosis of vaginal atrophy and in the management of the related symptoms.
OPTIONS: The modalities of evaluation range from basic pelvic examination, examination of the vulva, and laboratory tests.
OUTCOMES: A comprehensive approach to the detection of vaginal atrophy and a discussion of available therapeutic and nontherapeutic options.
EVIDENCE: Published opinions of experts, supplemented by evidence from clinical trials, where appropriate.
VALUES: The quality of the Force on the Periodic Health Examination.
BENEFITS, HARMS AND COSTS: Diagnosis of vaginal atrophy is often a challenge because women are unwilling to report symptoms, which have the potential to significantly decrease their quality of life. Increased clinical suspicion is the first step in the diagnosis of vaginal atrophy, which will prompt the initiation of safe therapies with proven efficacy.
RECOMMENDATIONS: (1) Health-care providers should routinely assess postmenopausal women for the symptoms and signs of vaginal atrophy, a common condition that exerts significant negative effects on quality of life. (III-C) (2) Regular sexual activity should be encouraged to maintain vaginal health. (II-2B) (3) Women experiencing recurrent urinary tract infections should be instructed that consumption of pure cranberry-lingonberry juice, rather than cranberry drink, will decrease their risk of urinary infections. (I-A) (4) Vaginal moisturizers applied on a regular basis have an efficacy equivalent to local hormone replacement for the treatment of local urogenital symptoms such as vaginal itching, irritation, and dyspareunia, and should be offered to women wishing to avoid the use of hormone replacement therapy. (I-A) (5) Women experiencing vaginal atrophy can be offered any of the following effective vaginal estrogen replacement therapies: conjugated equine estrogen (CEE) cream (I-A), a sustained-release intravaginal estradiol ring (I-A), or a low-dose estradiol tablet. (I-A) (6) Although systematic absorption of estrogen can occur with local preparations, there is insufficient data to recommend annual endometrial surveillance in asymptomatic women using local estrogens. (III-C) (7) For menopausal women experiencing recurrent urinary tract infections and who have no contraindication to local hormone replacement, vaginal estrogen therapy should be offered. (I-A) VALIDATION: These guidelines have been reviewed by the joint committee of Clinical Practice Gynaecology and Urogynaecology and approved by the Execute and Council of the Society of Obstetricians and Gynaecologists of Canada.
SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.
Cobin RH, Futterweit W, Ginzburg SB, Goodman NF, Kleerekoper M, Licata AA, Meikle AW, Petak SM, Porte KL, Sellin RV, Smith KD, Verso MA, Watts NB; AACE Menopause Guidelines Revision Task Force.
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause.
Endocr Pract. 2006 May-Jun;12(3):315-37. doi: 10.4158/EP.12.3.315.
Abstract/Text
American College of Obstetricians and Gynecologists Women's Health Care Physicians.
Vasomotor symptoms.
Obstet Gynecol. 2004 Oct;104(4 Suppl):106S-117S. doi: 10.1097/01.AOG.0000138795.50777.af.
Abstract/Text
Weiderpass E, Baron JA, Adami HO, Magnusson C, Lindgren A, Bergström R, Correia N, Persson I.
Low-potency oestrogen and risk of endometrial cancer: a case-control study.
Lancet. 1999 May 29;353(9167):1824-8. doi: 10.1016/S0140-6736(98)10233-7.
Abstract/Text
BACKGROUND: Urogenital symptoms are common among postmenopausal women. Such symptoms may be alleviated by low-potency oestrogen formulations administered orally or vaginally. Although low-potency oestrogen formulations are assumed to have few, if any, adverse effects on the endometrium, risk of endometrial neoplasia has not been quantified.
METHODS: In a nationwide population-based case-control study in Sweden of endometrial cancer among postmenopausal women, we obtained detailed information on hormone replacement from 789 cases of endometrial cancer and 3368 population controls. In a histopathological review, 80 cases were reclassified as having endometrial atypical hyperplasia. Odds ratios and 95% CI were calculated with unconditional logistic regression.
FINDINGS: After multivariate adjustment, oral use of oestriol 1-2 mg daily increased the relative risk of endometrial cancer and endometrial atypical hyperplasia: the odds ratios for at least 5 years of use compared with never use were 3.0 (95% CI 2.0-4.4) and 8.3 (4.0-17.4), respectively. The association was stronger for well-differentiated cancers and those with limited invasion. The excess relative risk was lost rapidly after cessation of treatment. Only weak associations were observed between vaginal application of low-potency oestrogen formulations and relative risk of endometrial neoplasia.
INTERPRETATION: Oral, but not vaginal, treatment with low-potency oestrogen formulations increases the relative risk of endometrial neoplasia. Thus close surveillance of patients is needed, and addition of a progestagen should be considered.
