Showing posts with label Vulvovaginal atrophy. Show all posts
Showing posts with label Vulvovaginal atrophy. Show all posts

Monday, February 19, 2018

North American Menopause Society (NAMS) video series about important midlife health topics: Clinical options for treating GSM

The North American Menopause Society (NAMS) is proud of its comprehensive video series for women on important midlife health topics. All the interviews in the series are hosted by NAM Board of Trustees Member and Immediate Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

In this first video of 2018 series, Dr. Shapiro discusses clinical aspects of the genitourinary syndrome of menopause (GSM) with Dr.Nick Panay, an obstetrician-gynecologist from London and general secretary-elect of the international menopause society(IMS).

This is a very common problem worldwide, but it is severely underreported and undertreated because most of the women are reluctant to come forward and discuss it with the health care providers.

In this video, Dr. Panay discusses treatment options for women with GSM.





Monday, December 19, 2016

Applicator-free novel vaginal estradiol softgel capsule promising in relieving vaginal atrophy.

Vagicap. Courtesy: TherapeuticsMD

Vulvovaginal atrophy affects nearly half of the postmenopausal women in the United States.[1] It is often termed as ‘the silent epidemic’ as most of the women are reluctant to seek medical advice due to cultural, social reasons. Adverse publicity of Hormone Replacement Therapy(HRT) also plays a major role in preventing women from discussing the symptoms with a healthcare professional.[2]

Results of a phase 3 REJOICE trial investigating a novel drug delivery system for estradiol have shown promising results in relieving symptoms of postmenopausal vulvovaginal atrophy.

This product which goes by the name of TX-004HR is being developed by TherapeuticsMD, Inc, BOCA RATON, Florida. The results from the pivotal phase 3 Rejoice Trial were presented at Endocrine Society’s 98th Annual Meeting and Expo, being held April 1-4, 2016, in Boston and American College of Obstetricians and Gynecologists (ACOG) Annual Clinical and Scientific Meeting held May 14-17, 2016, in Washington, DC.

TherapeuticsMD is using the unique technology called ‘SYMBODA’ in manufacturing the softgel capsules conditionally named as Yuvvexy™. SYMBODA, meaning “similar to the body,” is a solubilized female hormone technology for formulation of estradiol and progesterone identical in chemical structure to the estradiol and progesterone that women naturally produce.[3]  The drugs are dissolved in medium-chain oils enabling content uniformity and accurate dosing. Vagicap is an applicator free, vaginal-mucosal adhesive, soft gel capsule containing low-dose solubilized 17β-estradiol.[4]

Applicator free Vagicap . TherapeuticsMD

The results of the trial were published online in the forthcoming issue of Menopause. REJOICE was a randomized, double-blind, placebo-controlled, phase 3 study of 764 postmenopausal women who complaint of bothersome dyspareunia and vulvovaginal atrophy (VVA). They were treated with 4, 10, or 25 [mu]g TX-004HR or placebo for 12 weeks. Women received treatment once daily for 2 weeks, then twice weekly for 10 weeks.

Female Sexual Function Index (FSFI) questionnaire were administered to all the participants at baseline and at 12 weeks. It consists of 19 questions covering six domains of sexual function.
Significant improvement was seen (P < 0.0001) in co-primary endpoints of percentages of superficial and parabasal cells, vaginal pH other than dyspareunia at 2 weeks.

Dyspareunia, vaginal dryness and irritation all improved at the end of study. FSFI scores also showed a significant improvement with all the doses of TX-004HR.

The drug was well tolerated with no serious side effects. Blood levels of estradiol remained at pretreatment level throughout the study.

The authors concluded that “The present Female Sexual Function Index (FSFI) data coupled with improvement in vaginal physiology suggest that TX-004HR could be a promising treatment option for VVA, with a potential added benefit of improving Female Sexual Dysfunction (FSD) in postmenopausal women.

Dr Bernick, Julia M. Amadio and Sebastian Mirkin, MD are employed by TherapeuticsMD.






[1] http://www.endocrinologyadvisor.com/endo-2016/endo-vaginal-capsule-may-relieve-vulvar-vaginal-atrophy/article/490044/
[2] https://core.ac.uk/download/pdf/36770934.pdf
[3] https://www.therapeuticsmd.com/research/symboda-technology
[4] http://www.sciencedirect.com/science/article/pii/S1743609516304040

Monday, June 13, 2016

Menopause and the changing Vaginal Microbiome

With the increase in average life expectancy of women worldwide, it is estimated that 1.2 billion women will be menopausal or postmenopausal by the year 2030. About 85% of whom will experience at-least one menopausal symptom in lifetime. In US alone about 40 to 50 million women are estimated to suffer from vasomotor symptoms.
A recent review published in the forthcoming issue of Maturitas, The European menopause Journal  compares the  changes in vaginal microbiome with approaching menopause, the role of hormone replacement therapy in vaginal bacterial community  and role of probiotics in reinstating the homeostasis.

The vaginal microbiome plays an important role in women’s life, right from puberty to menopause. The diversity, abundance and composition of the microbial species in vagina varies dramatically. One of the original NIH-funded Human MicrobiomeProject (HMP) targeted sites for characterization of the microbiota was the vagina.

The relationship between the vaginal microbiome and menopause occurs predominantly through estrogen. During reproductive years, production of lactic acid and hydrogen peroxide by lactobacilli help maintain a strong barrier to pathogenic bacteria by maintaining a vaginal pH of 3.8 to 4.5. 

During the perimenopause women experience hormonal fluctuations, with decline in estrogen levels leading to a progressive decrease in acid-producing bacteria and pH rises >4.6 – this disrupts the vaginal micro-habitat and can lead to problems such as bacterial vaginosis. Normal flora has a dominance of various Lactobacilli, while in bacterial vaginosis (BV) microbiota is dominated by Gardnerella vaginalis and includes a number of anaerobic organisms.

In reproductive age women the microbial species in vagina can be grouped in five consistent groupings, referred to by Ravel et al as community state types (CSTs). Out of the 5 CSTs, the first four have higher proportion of Lactobacillus species whereas the fifth (CST IV) has lower proportions of Lactobacillus spp. and higher proportions of anaerobic organisms including Mobiluncus spp., and Atopobium vaginae.

As women progress towards premenopause and menopause, the composition of the VMB undergo significant change and play an important role in vulvovaginal atrophy. Postmenopausal hypoestrogenism causes a cascade of events that starts with thinning of the vaginal epithelium, leading to a smaller contribution of glycogen and higher alkaline pH that inhibits the growth of Lactobacillus.

Rebecca Brotman is an epidemiologist and infectious disease expert by training has worked and researched extensively on Vaginal Microbiome and its role in reproductive tract infection through various stages of women’s life. She is interested in intervention in VMB in context of meeting many of the challenges of premeopausal and menopausal life. 
  
In a study by Brotman R.M et al significant association was found between vaginal bacterial composition with menopause stage and signs of vaginal atrophy. A distinctive community state type CST IV-A was identified which was highly associated with signs of Vulvo Vagianl Atrophy (VVA) and was predominant in post-menopausal women. CST IV-A is a low Lactobacillus state and is known by a higher abundance of genera including Anaerococcus, Peptoniphilus and Prevotella, which could be playing a pivotal role in the clinical presentation of VVA.

It was also seen that compared to women with no VVA, the odds of CST of women with atrophy being classified as CST IV-A was 25 times more than being labellled as CST I.

This study provides a valuable insight into further research and studies to modulate and restore VMB homeostasis to understand and treat VVA in postmenopausal women.

It is well known that estrogen therapy is effective for the treatment of VVA and concomitantly, hormonal replacement increases the abundance of vaginal Lactobacillus species. Oral and vaginal probiotics holds considerable promise as a therapeutic modality for future in restoring the vaginal microbiome.  However additional trials are required before bacterial therapeutics can find its way into treatment armament species.

Several small RCTs have shown the effect of combination of ultra-low-dose vaginal estriol 0.03 mg in combination with viable Lactobacillus acidophilus to treat vaginal atrophy is superior to placebo. But, larger studies and meta-analysis are still awaited.

To date, a 2 strain combination of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 have proved to be the most effective at restoring and maintaining a normal vaginal microbiota.

Science has yet not solved all the interactions between body and the microbiome. It is so complex that it will take many more years to understand the implications of this symbiosis and devising effective therapeutics.


References:



Thursday, January 14, 2016

Intravaginal dehydroepiandrosterone (DHEA) relieves women of postmenopausal pain, dryness and atrophy.



The most bothersome symptoms of menopause is moderate to severe pain due to vulvovaginal atrophy and other genitourinary symptoms causing dysparunia. Local estrogens increase blood hormonal level even in the lowest possible dose  and systemic hormone therapy has its own shortcoming. 

A study published in December issue of Menopause by Labrie F et al aims to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy.

This is a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial.

325 women were registered as the study subjects and they used daily intravaginal 0.5% DHEA (6.5 mg) as suppositories for 12 weeks while 157 women who served as control used placebo.

There was a significant improvement in all the parameters tested like dysparunia, vaginal dryness and vaginal pH.

At physical examination the gynecologists saw an improvement in vaginal secretions, epithelial integrity, epithelial surface thickness, and color all by 86% to 121% over placebo (P < 0.0001).

Vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001) on a scale of 0-3.

Serum steroid level also remained in the menopausal range.

Local DHES, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids, which remain well within the normal postmenopausal range. This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological androgenic component to therapy.


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