News from NAMS 2018: Estetrol, the next generation hormone therapy linked to significant improvement in menopausal VMS

Estetrol (E4) (Donesta®) in daily oral dose of 15 mg appears to be the most effective dose for the treatment of menopausal VMS reports the results of Phase IIb (E4 Relief) clinical trial presented at the 29th Annual Meeting of the North American Menopause Society (NAMS), being held on 3-6 October 2018 in San Diego, CA.  

Estetrol (E4) is the first promising NEST™ or Native Estrogen with Selectively action in Tissues produced by the human fetal liver, crossing the placenta and excreted in maternal urine at relatively high levels during pregnancy. It has a half-life of 28 hours and exhibits a unique mode of action.

It acts as an estrogen agonist in the vagina, endometrium, bone, and cardiovascular system and shows a mixed agonist and antagonist estrogenic property in liver and breast tissue. This results in lower level of breast stimulation with no effect on hemostasis parameters and triglycerides levels.

This multicentric, randomized, placebo-controlled, double-blinded, dose-finding study Phase IIb clinical trial recruited post-menopausal women, aged 40-65years across many European countries. Women qualified to participate in the trial if they had ≥7 moderate to severe hot flushes (HF) per day, or ≥50 moderate to severe HF in the week and Transvaginal Ultrasound (TVUS) showed a bi-layer endometrial thickness ≤5 mm.

Women were randomized to receive 2.5; 5; 10; or 15 mg E4, or placebo, once-daily, for 12 weeks. The primary endpoints were decreased in frequency and severity of hot flashes (VMS), while effects on genitourinary symptoms, lipid and glucose metabolism, hemostatic and bone markers were secondary endpoints of interest. Menopause Rating Scale (MRS) assessed the health-related quality of life. Safety of the drug was assessed by measuring the endometrial thickness and bleeding episodes while on therapy. 

As a protective measure against endometrial hyperplasia, the patients receive 2 weeks of progestin therapy (Dydrogesterone 10 mg) after the cycle of E4 is complete.

Of the 257 women selected, 200 women completed the study. At the end of the study period, there was an 80% improvement in frequency and severity of hot flashes, vaginal dryness, and dyspareunia in the E4 15mg group as compared to placebo. The improvement in VMS started as early as the end of 2 weeks with a trend reaching significance at the end of 4 weeks.

All the 11 dimensions of MRS also showed improvement with a near 50% reduction in the total score. The drug was completely safe with no effect on total triglycerides and cholesterol panel, hemostatic parameters and endometrial hyperplasia.

Estetrol (E4) (Donesta®) could be the next breakthrough for treatment of the full spectrum of menopausal symptoms. It is wholly natural and safety profile differs from that of estrogen. It could be the next oral alternative for transdermal estrogen preparations because of more breast safety.

Maud Jost, E4 Program Director, commented: “The presentation of data from the E4 Relief trial provides further evidence of the potential of Estetrol in the treatment of menopausal symptoms. This is the second-high profile conference where our compelling data from our promising Donesta program is presented. Preparations are already underway to progress Donesta into Phase III trials, which if approved could provide an innovative alternative to the millions of women seeking treatment with an improved benefit and risk profile.” 

Mithra (Euronext Brussels: MITRA), is a company specialized in Women’s Health is headquartered in Liège, Belgium.

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News from NAMS 2018: Interferential current relieves dyspareunia in women with Premature ovarian insufficiency

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Women who have premature ovarian insufficiency (POI) face an array of problems including infertility, an early risk of a CVD event, vulvovaginal atrophy (VVA) and painful sexual intercourse due to insufficient estrogen levels. Dyspareunia is still reported while on HRT and limits the ability to enjoy sex and achieve orgasm.

Vaginal estriol cream is the most commonly prescribed treatment to increase lubrication and relieve the symptoms associated with estrogen deficit.

A new form of treatment with the help of Interferential current now offers hope by improving lubrication; thereby, reducing pain and increased the frequency of satisfying sexual encounters.

Researchers from the University of Campinas, commonly called Unicamp, in São Paulo, Brazil recruited women between the ages of 18 and 50 with POI and taking HRT for this small RCT. Initially, 80 women were selected out of which 35 included in the study. The women were asked to fill out a sexual function questionnaire (FSFI) and randomized to receive either Interferential current (IC) compared to topical estrogen cream (E).

IC group received electrical stimulation of the pelvic floor, in a total of 8 sessions of 20 minutes each for a month. Women in the E group used .5mg of topical estrogen per day for four weeks.

The researchers looked at improvements in lubrication and sexual function score, and relief from pain during physical intimacy. Data analysis showed that while lubrication and dyspareunia improved significantly in both the groups, there was not much improvement in the FSFI scale for women on local estrogen therapy.

However, there was a significant improvement in pre and post-intervention FSFI scores among women who received interferential current therapy (p=0.0004). These women also reported a significant improvement in sexual satisfaction and frequency of orgasm thus enabling the increase in sexual activity.

“We were encouraged with these results as they reveal a new alternative for the treatment of sexual complaints,” says Dr. Helena Giraldo, lead author of the study.

“Although this was a small study, it opens the door for further research that will help identify more options for women to help improve their overall quality of life by making their sexual experience more enjoyable,” says Dr. JoAnn Pinkerton, NAMS executive director.

The study was also presented at the 18th World Congress of Gynecological Endocrinology in Florence, Italy.

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NAMS 2018 annual meeting kicks off in San Diego, California

The North American Menopause Society Annual Scientific Meeting kicks off today in San Diego, California. The agenda is packed with symposiums, lectures, research presentations, and debates over many challenging topics related to health and quality of life of women at midlife and beyond.

The conference theme is Innovation, Evidence, and Individualization: Moving Menopause Management Forward and begins Wednesday, October 3, from 8:00 AM to 1:00 PM with pre-Meeting organized by the 2018 Pre-Meeting Co-Chair, Sheryl Kingsberg, Ph.D. on female sexuality.

The presentation will address various aspects of the critical topics including the epidemiology and classification of hypoactive sexual desire disorder (HSDD).

The focus is to make the gynecologist comfortable about talking on the topic with patients.   The six speakers from different discipline of medicine will cover biopsychosocial approach to treating hypoactive sexual desire disorder (HSDD) in postmenopausal women, pharmacologic and nonpharmacologic options for arousal and orgasm issues, the role of the physical therapist in female sexual function and dysfunction, treatment options for sexual problems resulting from genitourinary syndrome of menopause, and testosterone for HSDD: clinical perspectives from sexual medicine and gynecology.

Elissa Epel, Ph.D., from the University of California, San Francisco will talk about Telomere lengths, their role in aging process and psychological aspects of aging in her keynote address “Healthy Longevity and Telomeres: what does sex have to do with it.”

Symposiums are scheduled throughout the conference to discuss critical midlife topics like the role of stress in cardiovascular health of women, breast health, bone health, osteoporosis and increasing rate of hip fractures, and obesity and weight loss.

The Friday morning breakfast is reserved for ‘Trauma-informed care’ including the #MeToo discussion to help physician deal effectively with women who have suffered adverse sexual event, rape or abuse.

Looking forward to some very interesting abstracts presented at the conference.

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