Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy

Pinkerton, JoAnn V.; Stanczyk, Frank Z.

doi:10.1097/gme.0b013e31829755ed

Cited by 37 publications

(56 citation statements)

References 78 publications

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“…SERMs are a heterogeneous group made up of nonsteroidal compounds mostly which act as estrogen receptor (ER) ligands but were developed as targeted therapies 34. In other words, contrary to estrogens, which usually have an agonist activity, SERMs exert a mixed agonist or antagonist action depending on the target tissue 35–38.…”

Section: Treatment Optionsmentioning

confidence: 99%

Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy

Palacios

Cancelo

2016

IJWH

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The physiological decrease in vaginal estrogens is accountable for the emergence of vulvar and vaginal atrophy (VVA) and its related symptoms such as vaginal dryness, dyspareunia, vaginal and/or vulvar irritation or itching, and dysuria. The repercussion of these symptoms on quality of life often makes it necessary to initiate treatment. Up until now, the treatments available included vaginal moisturizers and lubricants, local estrogens, and hormonal therapy. However, therapeutic options have now been increased with the approval of 60 mg ospemifene, the first nonhormonal oral treatment with an agonist effect on the vaginal epithelium and an endometrial and breast safety profile which makes it unique. This is the first selective estrogen receptor modulator indicated in women with moderate-to-severe vaginal atrophy not eligible for local estrogen treatment. Considering that “local estrogen noneligible women” are those in whom such treatment cannot be administered either because it is contraindicated or due to skill issues, who are averse to the mode and convenience of vaginal products’ administration or to their use on account of potential systemic absorption, or those who demonstrate dissatisfaction in terms of efficacy and safety, it is clear that there is a significant unmet medical need in VVA management. In fact, a great number of women show lack of adherence, dropping out of at least one VVA treatment, including nonhormonal moisturizers and lubricants, which they consider to be ineffective and uncomfortable. If they could choose, many of them may opt for oral treatment. In Phase III studies, ospemifene demonstrated efficacy in vaginal dryness and dyspareunia, regenerating vaginal cells, improving lubrication, and reducing pain during sexual intercourse. Symptoms improved in the first 4 weeks and endured for up to 1 year. Additionally, it demonstrated a good endometrial, cardiovascular system, and breast safety profile.

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Section: Treatment Optionsmentioning

confidence: 99%

Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy

Palacios

Cancelo

2016

IJWH

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“…Of the available SERMs that have been evaluated for effects on VVA, the recently marketed, orally administered ospemifene shows the most targeted beneficial effects when used alone. 1 In contrast to vaginal preparations containing estrogen to treat VVA, the newly developed drug Prasterone (Endoceutics, Quebec, Canada) contains a low dose (6.5 mg) of dehydroepiandrosterone (DHEA), which is administered daily intravaginally. Studies with this preparation show clinical benefits on US FDA-recognized parameters of VVA, specifically a decrease in the percentage of vaginal basal cells, an increase in the percentage of vaginal superficial cells, a decrease in vaginal pH, and an improvement in moderate-tosevere dyspareunia and vaginal dryness.…”

mentioning

confidence: 99%

Effect of intravaginal dehydroepiandrosterone treatment on the endometrium

Stanczyk

2015

Menopause

Self Cite

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“…The clinical pharmacological agents that target NRs-popularly known as selective receptor modulators-selectively agonize or antagonize their cognate receptors in a tissue-, cell type-, and promoter-specific manner [comprehensively reviewed by Burris et al (2013)]. Selective estrogen receptor modulators have found clinical application in estrogen receptor (ER)-positive [tamoxifen (Burris et al, 2013)] and metastatic [toremifene (Mustonen et al, 2014)] breast cancer, osteoporosis [raloxifene (Gizzo et al, 2013)], and vaginal atrophy [lasofoxifene (Pinkerton and Stanczyk, 2014)]. Given their robust antagonism of these signaling conduits in cells mediating the immune and inflammatory responses-B cells, T cells, and macrophages-a variety of glucocorticoid receptorspecific selective receptor modulators is in active clinical use for inflammatory and allergic conditions of the respiratory system (e.g., asthma, rhinitis) and skin (acne, psoriasis) and autoimmune disorders (rheumatoid arthritis), and to suppress local inflammatory responses in musculoskeletal injuries (Burris et al, 2013).…”

Section: Clinical Pharmacology Of Nr Signaling Pathwaysmentioning

confidence: 99%

Research Resources for Nuclear Receptor Signaling Pathways

McKenna

2016

Mol Pharmacol

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Nuclear receptor (NR) signaling pathways impact cellular function in a broad variety of tissues in both normal physiology and disease states. The complex tissue-specific biology of these pathways is an enduring impediment to the development of clinical NR small-molecule modulators that combine therapeutically desirable effects in specific target tissues with suppression of off-target effects in other tissues. Supporting the important primary research in this area is a variety of webbased resources that assist researchers in gaining an appreciation of the molecular determinants of the pharmacology of a NR pathway in a given tissue. In this study, selected representative examples of these tools are reviewed, along with discussions on how current and future generations of tools might optimally adapt to the future of NR signaling research.

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Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy

Abstract: SERMs that specifically target the pathophysiology underlying VVA may provide an alternative to vaginal or systemic estrogen therapy.

Cited by 37 publications

References 78 publications

Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy

Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy

Effect of intravaginal dehydroepiandrosterone treatment on the endometrium

Research Resources for Nuclear Receptor Signaling Pathways

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