Vaginal Estrogen Use Research Articles

Hormone therapy in survivors of gynaecological and breast cancer

Key content Gynaecological and breast cancers affect premenopausal and perimenopausal women at rates ranging 15–70% and treatment often causes the abrupt onset of menopause. Available studies do not show an increase in recurrence or decrease in survival among women with endometrial, ovarian or cervical cancer who use hormone replacement therapy (HRT). Data regarding the risks of systemic HRT in survivors of breast cancer are varied, and an increase in breast cancer recurrence with the use of systemic HRT has been demonstrated in randomised controlled trials. Limited data exist regarding the use of vaginal estrogen, however, no effect on recurrence has been demonstrated. The decision regarding the use of HRT in women with cancer must be individualised and should take into account issues regarding quality of life. Learning objectives To review the evidence regarding the cancer‐specific risks, that is, recurrence or death, of HRT in survivors of gynaecological and breast cancer. To provide recommendations for the use of HRT in survivors of gynaecological and breast cancer. Ethical issues How to balance the risks of HRT with quality of life concerns in survivors of gynaecological and breast cancer when evidence to guide our recommendations is limited?

From systemic hormone therapy to vaginal estrogen – A nationwide register study in Finland, 2003–2012

ObjectivesTo assess the patterns of use of reimbursed systemic hormone therapy (HT) and vaginal estrogen preparations among women aged 45 and older in Finland. Study designReimbursed purchases of prescribed systemic HT and vaginal estrogen preparations for the years 2003–2012 were obtained from a nationwide prescription registry. Systemic preparations included estrogen patches, gels and tablets, tibolone, continuous combination preparations and sequential combination preparations. Prescribed vaginal estrogens included a vaginal ring and vaginal tablets. Main outcome measuresAnnual period prevalence for systemic HT and vaginal estrogen use. ResultsThe total prevalence of prescribed HT use remained relatively constant (at 26−27%) throughout the studied period, but the share of women using systemic preparations decreased from 21% to 12%, while the share of women using vaginal estrogens increased from 9% to 19%. Decreases were observed for all classes of systemic preparations, although the decrease was largest for sequential combination preparations (from 4.9% to 1.6%) and estrogen tablets (from 5.2% to 2.9%). Continuous combination preparations remained the most commonly used types of systemic preparation (5.4−4.2%). Systemic HT use decreased most among 45−49 year old women (9.5–4.3%), while the use of vaginal estrogens increased most among those aged 65 and over. ConclusionsBased on the register data, the trends in HT use indicate changed prescribing patterns in accordance with clinical guidelines. It is notable that since 2009, vaginal estrogen was more commonly prescribed than systemic HT.

SP34-3 Treatment and prevention for urinary tract infection in children

Recurrent lower urinary tract infections in women are a highly prevalent and burdensome condition for which best practice guidelines for treatment and prevention that minimize harm and optimize well-being are greatly needed. To inform development of practice recommendations, a rapid literature review of original research, systematic reviews, meta-analyses and practice guidelines was conducted.PubMed®, Embase®, Opus, Scopus®, Google Scholar, The Cochrane Library and the U.S. National Guideline Clearinghouse electronic databases were searched from inception to September 22, 2017. Articles and practice guidelines were included if they were in English, were peer reviewed, included women, involved treatment or prevention strategies for recurrent urinary tract infection and reported an outcome related to recurrence rates of urinary tract infection. Critical appraisal of original studies was conducted using the Cochrane risk of bias tool, and of systematic reviews using the AMSTAR 2 tool.Of 1,582 citations identified 74 met our study inclusion criteria. These comprised 49 randomized controlled trials, 23 systematic reviews (16 with meta-analyses) and 2 practice guidelines. No study reported a multi-targeted treatment approach. There was a lack of high quality studies and systematic reviews evaluating prevention strategies for recurrent urinary tract infection.We recommend an algorithmic approach to care that includes education on lifestyle and behavioral modifications, and addresses specific populations of women with antimicrobial based and nonantibiotic alternatives. This approach includes the use of vaginal estrogen with or without lactobacillus containing probiotics in postmenopausal women, low dose post-coital antibiotics for recurrent urinary tract infection associated with sexual activity in premenopausal women, low dose daily antibiotic prophylaxis in premenopausal women with infections unrelated to sexual activity, and methenamine hippurate and/or lactobacillus containing probiotics as nonantibiotic alternatives. Future research should involve consistent use of terminology, validated instruments to assess response to interventions and patient perspectives on care. Our treatment algorithm is based on the best available evidence, and fills a gap in the literature and practice regarding effective strategies to prevent recurrent urinary tract infection in women.

Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview

ABSTRACTVulvovaginal atrophy-related symptoms exert a negative impact on the quality of life of up to 50% of postmenopausal women. Many of them decline to use topical vaginal estrogen, which is the standard effective therapy, due to the adverse publicity over recent years, and seek for alternatives. Further, there are no safety studies to support the use of topical vaginal estrogen in breast cancer survivors, and it is considered as contraindicated by many health-care professionals. Vaginal moisturizers and lubricants as well as regular sexual activity may be helpful to such women. Vaginal moisturizers may have an equivalent efficacy to topical vaginal estrogen and should be offered to women wishing to avoid the use of hormonal therapy. Lubricants are usually used during sexual intercourse to provide temporary relief from vaginal dryness and dyspareunia; however, they have no long-term therapeutic effects. We provide in this systematic review up-to-date information, for women and health-care professionals, about the use, safety and efficacy of the available vaginal moisturizers and lubricants.

Hormone replacement therapy and risk of new-onset atrial fibrillation after myocardial infarction--a nationwide cohort study.

ObjectivesOur aim was to assess the association between use of hormone replacement therapy (HRT) and risk of new-onset atrial fibrillation (AF) after myocardial infarction.Design, Setting and ParticipantsWe used Danish nationwide registers of hospitalizations and prescriptions to identify all women admitted with myocardial infarction in the period 1997 to 2009 and with no known diagnosis of AF. Their use of overall HRT and HRT categories was assessed. Multivariable Cox proportional hazards analysis was used to calculate the risk of new-onset AF first year after discharge, comparing use of HRT to no use.Main Outcome MeasuresNew-onset atrial fibrillation.ResultsIn the period 1997 to 2009, 32 925 women were discharged alive after MI. In the first year after MI, new-onset AF was diagnosed in 1381 women (4.2%). Unadjusted incidence rates of AF decreased with use of HRT (incidence rate 37.4 for use of overall HRT and 53.7 for no use). Overall HRT was associated with a decreased risk of AF (HR 0.82, 95% confidence interval [CI] 0.68–1.00). The lowest risk of AF was found in women ≥80 years old for use of overall HRT and vaginal estrogen (HR 0.63, CI 0.42–0.94, and HR 0.58, CI 0.34–0.99, respectively). Decreased risk of AF with use of overall HRT and HRT categories was also found in other age groups.ConclusionsUse of HRT is associated with a decreased risk of new-onset AF in women with myocardial infarction first year after discharge. The underlying mechanisms remain to be determined. Unmeasured confounding might be one of them.

Abstract ES4-1: Navigating the Obstacles and Risks of Survivorship: Breast Cancer Sexuality: Issues and Answers

Abstract The sexual consequences of breast cancer and its treatments are well known. Sexual difficulties include alteration in hormonal levels, changes in sexual organs and anatomy, vaginal and vulvar dryness, changes in libido, increased latency to orgasm and decreased intensity of orgasmic response. Changes in body image, sexual self-esteem and relationship dynamic tension may present as survivorship challenges for the breast cancer patient and her partner. Severe vulvo vaginal and clitoral atrophy as a result of chemotherapy and/or adjuvant hormone therapy, and loss of libido secondary to dyspareunia are widespread. Cytostatic medications that are prescribed for long-term use (aromatase inhibitors) can impact bone health, sexual functioning/satisfaction and overall quality of life. Many women on aromatase inhibitors have severe complaints of vulvar and vaginal atrophy. Sexual dysfunction is common for breast cancer population and limited acceptable treatments are available. Minimally absorbed local vaginal estrogen use in this population remains controversial and a hotly debated controversial topic. More data should be forthcoming. There are multiple new innovative treatments in the research pipeline for female sexual dysfunction. DHEA intravaginal suppositories, Flibanserin and Bremelanotide (PT 141) remain promising although they have not been adequately studied in the breast cancer population. Ospemifene a novel estrogen agonist/ antagonist has demonstrated a strong estrogenic effect on the vaginal epithelium during a three month trial period and did not stimulate the endometrium; however, the medication did mildly aggravate hot flashes (this did not lead to drug discontinuation). Although not studied in breast cancer patients, pivotal Phase 3 data confirmed effectiveness of ospemifene as effective treatment for vulvovaginal atrophy. In a recent article in Menopause, Ospemifene and 4-hydroxyospemifene effectively prevented and treat breast cancer in Mtag. TG Transgenic Mouse. Testosterone use remains off label and is not FDA approved, yet it is widely used in the non cancer population. New emerging safety data will be presented. Vaginal moisturizers, lubricants and dilators in association with genito pelvic floor therapy and intravaginal valium suppositories can be considered front line treatment for atrophy, dyspareunia and hypertonic vaginismus. New innovative data on non hormonal management of hot flashes is and important initial step in the overall management of the breast cancer patient who is suffering from sexual dysfunction. A multi model treatment paradigm will be presented which will include pharmacologic, nonpharmacologic, and psychosocial interventions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES4-1.

EMAS clinical guide: Low-dose vaginal estrogens for postmenopausal vaginal atrophy

Vaginal atrophy is common in postmenopausal women. This clinical guide provides the evidence for the clinical use of vaginal estrogens for this condition focussing on publications since the 2006 Cochrane systematic review. Use after breast cancer, before assessment of cervical cytology and prolapse surgery is also discussed.

Management of vaginal dryness and dyspareunia in estrogen sensitive cancer patients

Cancer patients suffer from vaginal dryness and dyspareunia earlier and longer than the general population, with more severe and distressing symptoms. Life-style advices are the first step and vaginal lubricants can be tried, but they can’t completely relieve atrophic symptoms. The most effective therapy is use of vaginal estrogens, but compliance and management are particularly difficult in estrogen sensitive cancer patients because of their systemic absorption. Compliance can be improved if they are begun at a very low dose and gradually increased until the lowest effective dose is reached. Promestriene only possesses an intramucosal effect, it can be used at very low doses in cancer patients suffering from urogenital symptoms.

Vaginal Estrogens for the Treatment of Dyspareunia

Vaginal atrophy, which is associated with vaginal itching, burning, dryness, irritation, and pain, is estimated to affect up to 40% of postmenopausal women. Estrogens play a key role in maintaining vaginal health; women with low serum estradiol are more likely to experience vaginal dryness, dyspareunia, and reduced sexual activity compared with women who have higher estradiol levels. The purpose of this review is to assess the prevalence and impact of dyspareunia, a symptom of vaginal atrophy, on the health of postmenopausal women and to evaluate treatment options using vaginal estrogens (U.S. Food and Drug Administration [FDA] approved). Relevant published literature was identified by searching Index Medicus using the PubMed online database. The search terms dyspareunia, vaginal estrogen, vaginal hormone therapy, vaginal atrophy, and atrophic vaginitis were the focus of the literature review. Current treatment guidelines for vaginal atrophy recommend the use of minimally absorbed local vaginal estrogens, along with non-hormonal lubricants or moisturizers, coupled with maintenance of sexual activity. Vaginal estrogen therapy has been shown to provide improvement in the signs and symptoms of vaginal or vulvar atrophy. Vaginal tablets, rings, and creams are indicated for the treatment of vaginal atrophy, and the FDA has recently approved a low-dose regimen of conjugated estrogens cream to treat moderate-to-severe postmenopausal dyspareunia. The use of low-dose vaginal estrogens has been shown to be effective in treating symptoms of vaginal atrophy without causing significant proliferation of the endometrial lining, and no significant differences have been seen among vaginal preparations in terms of endometrial safety. Women should be informed of the potential benefits and risks of the treatment options available, and with the help of their healthcare provider, choose an intervention that is most suitable to their individual needs and circumstances.

Systemic effects of vaginally administered estrogen therapy: a review.

Hormone therapy was considered the standard of care before the publication of the Women's Health Initiative. After the study was published, the use of systemic hormone therapy dramatically decreased resulting in an increased incidence of menopausal symptoms such as hot flashes, vaginal dryness, and dyspareunia experienced by women. Use of vaginal estrogen offers women a unique alternative for relief of these symptoms. This article reviews the systemic effects of vaginally administered estrogen. Effects on serum hormone levels, vasomotor symptoms, lipid profiles, and use in women with breast cancer are reviewed. An accompanying review (J Pelvic Med Surg. 2009;15:105-114.) examines the local effects of vaginally administered estrogen.

Effects of vaginal estrogen use on the lower urinary tract in post-menopausal women

Objective To study the effects of vaginal estrogen application on blood flow of the lower urinary tract in post-menopausal women. Methods Arterial blood flow frequency spectrum, peak systolic blood flow, end-diastolic blood flow velocity and resistance index of the peri-urethra and neck of the urinary bladder, as well as changes in their genitourinary system, were measured with color Doppler ultrasound imaging in post-menopausal women before and three months after their use of premarin ointment containing natural estrogen per vagina. Results Three months after treatment with estrogen-premarin ointment per vagina in post-menopausal women, their peak systolic blood flow velocity of the peri-urethra arteries increased to 13.23 cm/s from 11.94 cm/s before treatment, end-diastolic blood flow velocity increased to 3.92 cm/s from 1.91 cm/s and resistance index decreased to 2. 79 from 3. 84 (P <0. 01 ). And, their peak systolic blood flow velocity of the arteries of the neck of the urinary bladder increased to 17.09 cm/s from 12. 77 cm/s before treatment, end-diastolic blood flow velocity increased to 2. 83 cm/s from 1.31 cm/s and resistant index decreased to 2. 78 from 3.78 (P<0.01). It indicated that local vasodilatation and decrease dresistance of the lower urinary tract made blood flow of the arteries of the peri-urethra and neck of the urinary bladder increase, urinary frequency and nocturia occurrence decrease, and sexual satisfaction improve.Conclusions Blood flow, symptoms of the lower urinary tract and their quality of life can be improved in post-menopausal women after treatment with natural estrogen-premarin ointment per vagina. Key words: Menopause; Estrogens; Admitistration, intravaginal; Regional blood flow; Ultrasonography, Doppler, Color

Urinary Incontinence and Diabetes in Postmenopausal Women

This study evaluates diabetes characteristics and other risk factors for urinary incontinence among community-dwelling postmenopausal women. We performed a cross-sectional analysis of a population-based study of 1,017 postmenopausal women (218 with diabetes), aged 55-75 years, enrolled from a health maintenance organization. Outcomes included any incontinence and severe incontinence in the prior month. Overall, 60% of women had any incontinence in the prior month and 8% had severe incontinence. Parity and postvoid residual bladder volume were not associated with incontinence. Oral estrogen and vaginal estrogen use were positively associated with a report of any incontinence but not severe incontinence. A history of urinary tract infection (UTI) and measures of general health were associated with both outcomes. Women with diabetes reported disproportionately more severe incontinence, difficulty controlling urination, mixed (stress and urge) incontinence, use of pads, inability to completely empty the bladder, being unaware of leakage, and discomfort with urination (P < or = 0.06). Diabetes duration, treatment type, peripheral neuropathy, and retinopathy were significantly associated with severe incontinence in multiple regression models adjusted for age, education, and history of UTI (P = 0.01-0.06); however, additional adjustment for BMI diminished the strength of association (P = 0.17-0.52). Urinary incontinence is highly prevalent among postmenopausal women. Women with diabetes are more likely to experience severe and symptomatic urinary incontinence. UTI history is a major risk factor, postvoid residual bladder volume plays no demonstrable role, and BMI confounds the relationship between diabetes and incontinence among healthy postmenopausal women.

Predictors of urinary tract infection after menopause: A prospective study

To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women. We conducted a population-based, prospective cohort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and followed for 2 years. A wide range of behavioral and physiologic exposures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months. During 1773 person-years of follow-up, 138 symptomatic urinary tract infections occurred (incidence, 0.07 per person-year). Independent predictors of infection included insulin-treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.8; 95% CI: 1.0 to 3.4), a history of kidney stones (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteriuria at baseline (HR = 1.8; 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment. Insulin-treated diabetes is a potentially modifiable risk factor for incident acute cystitis among postmenopausal women, whereas a lifetime history of urinary tract infection was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physiologic factors was not associated with acute cystitis episodes in this generally healthy sample.

Effects of hormone replacement therapy on QT interval

We evaluated the electrocardiograms of 208 postmenopausal women (ages 40 to > or = 70 years) without heart disease, medications that could alter the QT interval, use of vaginal estrogens, unknown hormone replacement therapy, or electrocardiographic abnormalities both with (n = 76) and without (n = 132) hormone replacement therapy, and found no significant effects of hormone replacement therapy status on heart rate, QT interval, or the corrected QT interval. Thus, estrogen and/or progesterone effect does not explain the gender differences in myocardial repolarization.