Non-estrogen Therapies Research Articles

Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review

(Abstracted from Obstet Gynecol 2023;1(00):00) Genitourinary symptoms of menopause (GSMs) are common and include vaginal dryness, discomfort and dyspareunia, and urinary urgency and frequency. Women often do not seek treatment, although commercially available local estrogen products have been shown to be effective.

Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review.

To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM). MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators. We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group. Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO2) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function. Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.

A prospective controlled study of sexual function and sexually related personal distress up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

Premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) may impair sexual function, but the nature and degree of impairment and impact of estrogen therapy on sexual function and sexually related personal distress after RRBSO are uncertain. Prospective observational study of 73 premenopausal women at elevated risk of ovarian cancer planning RRBSO and 68 premenopausal controls at population risk of ovarian cancer. Participants completed the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. Change from baseline in sexual function following RRBSO was compared with controls at 12 months according to estrogen therapy use. Baseline sexual function domains did not differ between controls and those who underwent RRBSO and subsequently initiated (56.2%) or did not initiate (43.8%) estrogen therapy. At 12 months, sexual desire and satisfaction were unchanged in the RRBSO group compared with controls. After RRBSO, nonestrogen therapy users demonstrated significant impairment in sexual arousal (β-coefficient (95% confidence interval) -2.53 (-4.86 to -0.19), P < 0.03), lubrication (-3.40 (-5.84 to -0.96), P < 0.006), orgasm (-1.64 (-3.23 to -0.06), P < 0.04), and pain (-2.70 (-4.59 to 0.82), P < 0.005) compared with controls. Although sexually related personal distress may have been more likely after RRBSO, irrespective of estrogen therapy use, there was insufficient data to formally test this effect. The findings suggest premenopausal RRBSO adversely affects several aspects of sexual function which may be mitigated by the use of estrogen therapy. Further research is needed to understand the effects of RRBSO on sexual function and sexually related personal distress, and the potential for estrogen therapy to mitigate against any adverse effects.

What is the efficacy of nonestrogen therapy for treating AV in postmenopausal women?

What is the efficacy of nonestrogen therapy for treating AV in postmenopausal women?

Abstract P1-11-13: Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival

Abstract Background Survivors of ER-expressing operable breast cancer (ER+BC) generally do not receive hormone replacement therapy for menopausal symptoms due to concern about provoking recurrence of disease. Single dose depomedroxyprogesterone acetate (MPA) 400 mg IM has previously been shown (Loprinzi CL, et al. J Clin Oncol 2006;24:1409) to be the most effective non-estrogen therapy available for menopausal hot flashes (HF) but long-term evidence of safety in survivors of ER+BC is lacking. Methods Consecutive patients previously diagnosed with ER+BC who received MPA for HF between January 2007 and December 2012 were retrospectively identified in the breast cancer patient database at Mayo Clinic Arizona. Medical records were audited for breast cancer outcomes in these cases and in contemporaneous control patients with ER+BC who did not receive MPA, matched for age, stage of disease, and year of diagnosis. Statistical comparisons of local-regional recurrence and event-free survival were performed. Results 92 patients who received MPA were identified and matched 1:1 with contemporaneous controls. Median follow-up duration was 5.7 years in cases and 4.5 years in controls. Estimated local-regional recurrence free survival at 10 years was 85% (95% CI, 72-100%) in cases and 95% (95% CI, 86-100%) in controls. Matched pairs hazard ratio was 1.0 (95% CI, 0.06-16.0) for local-regional recurrence free survival. Estimated event-free survival at 10 years was 81% (95% CI, 69-97%) in cases and 76% (95% CI, 64-92%) in controls. Matched pairs hazard ratio was 0.38 (95% CI, 0.10-1.41) for event-free survival. The majority (77%) of case patients experienced satisfactory relief of hot flashes from MPA injection. Conclusion In this retrospective case-control study we were unable to identify a detrimental effect of MPA therapy for HF in survivors of ER+BC. MPA may be acceptable for management of HF in this population. Citation Format: Ertz-Archambault N, Rogoff L, Kosiorek H, Ernst B, Anderson K, Pockaj B, Gray R, Northfelt D. Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-13.

Endothelial Relaxation Mechanisms and Oxidative Stress Are Restored by Atorvastatin Therapy in Ovariectomized Rats

The studies on hormone replacement therapy (HRT) in females with estrogen deficiency are not conclusive. Thus, non-estrogen therapies, such as atorvastatin (ATO), could be new strategies to substitute or complement HRT. This study evaluated the effects of ATO on mesenteric vascular bed (MVB) function from ovariectomized (OVX) female rats. Female rats were divided into control SHAM, OVX, and OVX treated with 17β-estradiol (EST) or ATO groups. The MVB reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine staining, and the expression of target proteins by western blot. The reduction in acetylcholine-induced relaxation in OVX rats was restored by ATO or EST treatment. The endothelium-dependent nitric oxide (NO) component was reduced in OVX rats, whereas the endothelium-derived hyperpolarizing factor (EDHF) component or prostanoids were not altered in the MVBs. Endothelial dysfunction in OVX rats was associated with oxidative stress, an up-regulation of iNOS and NADPH oxidase expression and a down-regulation of eNOS expression. Treatment with ATO or EST improved the NO component of the relaxation and normalized oxidative stress and the expression of those signaling pathways enzymes. Thus, the protective effect of ATO on endothelial dysfunction caused by estrogen deficiency highlights a significant therapeutic benefit for statins independent of its effects on cholesterol, thus providing evidence that non-estrogen therapy could be used for cardiovascular benefit in an estrogen-deficient state, such as menopause.

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

Controversy exists about whether vaginal estrogens interfere with the efficacy of aromatase inhibitors (AIs) in breast cancer patients. With the greater incidence of vaginal atrophy in patients on AIs, a safe and effective nonestrogen therapy is necessary. We hypothesized that vaginal testosterone cream could safely treat vaginal atrophy in women on AIs. Twenty-one postmenopausal breast cancer patients on AIs with symptoms of vaginal atrophy were treated with testosterone cream applied to the vaginal epithelium daily for 28 days. Ten women received a dose of 300 μg, 10 received 150 μg, and one was not evaluable. Estradiol levels, testosterone levels, symptoms of vaginal atrophy, and gynecologic examinations with pH and vaginal cytology were compared before and after therapy. Estradiol levels remained suppressed after treatment to <8 pg/mL. Mean total symptom scores improved from 2.0 to 0.7 after treatment (p < .001) and remained improved 1 month thereafter (p = .003). Dyspareunia (p = .0014) and vaginal dryness (p <.001) improved. The median vaginal pH decreased from 5.5 to 5.0 (p = .028). The median maturation index rose from 20% to 40% (p < .001). Although improvement in total symptom score was similar for both doses (-1.3 for 300 μg, -0.8 for 150 μg; p = .37), only the 300-μg dose was associated with improved pH and maturation values. A 4-week course of vaginal testosterone was associated with improved signs and symptoms of vaginal atrophy related to AI therapy without increasing estradiol or testosterone levels. Longer-term trials are warranted.

Long-Term Effect of the Women's Health Initiative Study on Antiosteoporosis Medication Prescribing

To describe long-term prescribing patterns of osteoporosis therapy before and after the Women's Health Initiative (WHI) publication. We conducted a time-series analysis from 1997 to 2005 using nationally representative data based on office-based physician and hospital ambulatory clinic visits. Bivariate and multivariable analyses were conducted using chi-square tests and logistic regression, respectively, and trends in the prevalence of osteoporosis therapies were evaluated per 6-month (semiannual) intervals. Linear regression and graphic techniques were used to determine statistical differences in the prevalence trends between the two periods. Overall prevalence of therapeutic or preventive osteoporosis therapy was similar between the WHI periods. However, a significant decrease in estrogen therapy and increases in bisphosphonates, calcium/vitamin D were observed in the period after the WHI publication (p < 0.05). Multiple logistic regression analysis showed older age and white race were associated with a higher likelihood of antiosteoporosis medication (AOM) prescription, and Medicaid insurance type was associated with a lower likelihood of an AOM prescription. Excluding calcium/vitamin D, nonestrogen therapy was more likely to be prescribed in the after-WHI period (office-based physician clinic: [adjusted OR, aOR] 2.49 [2.04-4.04]; hospital-based clinic: aOR 2.42 [1.67-7.50]) Nonestrogen therapy was more prevalent in visits made by older women, women of white race, women with contraindicated conditions for estrogen therapy, and women from the Northeast region. After the WHI publication, the overall prevalence of osteoporosis therapy did not change; however, a shift from estrogen to nonestrogen therapy was observed after the WHI publication. Black women were less likely to receive nonestrogen antiosteoporosis therapy in hospital-based clinics.

Primary prevention of coronary heart disease in women

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses' Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50-59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.

Hormone replacement therapy.

An estimated 10 million women in the United States currently use hormone replacement therapy (HRT) for relief of menopausal symptoms or prevention of chronic disease conditions such as osteoporosis. 1 However, the early termination of the Women’s Health Initiative (WHI) study, which examined the use of estrogen as primary prevention for osteoporosis and other chronic conditions, has led to reevaluation of the use of exogenous estrogens. In January 2003, the United States Food and Drug Administration (FDA) revised the approved indications for estrogen alone or in combination therapy to include treatment of postmenopausal symptoms or prevention of osteoporosis, stating, “when these products are being prescribed solely for the prevention of postmenopausal osteoporosis…estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.” 1 The FDA recommended prescribing nonestrogen therapies (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, parathyroid hormone) for the treatment and prevention of osteoporosis in lower risk patients and advises use of estrogen therapy at the lowest dose for the shortest duration possible. 1

Alendronate vs. Calcitonin for Osteoporosis

Oral alendronate and nasal calcitonin are the 2 most commonly prescribed non-estrogen therapies for postmenopausal osteoporosis. In this randomized

General Medicine: Alendronate vs. Calcitonin for Osteoporosis

Oral alendronate and nasal calcitonin are the 2 most commonly prescribed non-estrogen therapies for postmenopausal osteoporosis. In this randomized trial, supported by the maker of alendronate, researchers compared the 2 treatments in 299 osteoporotic women (mean age, 64) who were …