Here are the top 5 posts this week.

Sperms used as vehicle for targeted drug delivery in gynecological cancers.

Sperms are not just for baby-making anymore, but can be used as cargo agents for delivering drugs inside the body.

Researchers at Institute for Integrative Nanosciences in Germany and Chemnitz University of Technology are working on innovative way to use sperms as cargo delivery agents to carry drugs through female reproductive tract.

https://obgynupdated.blogspot.com/2017/04/sperms-used-as-vehicle-for-targeted.html

New class of drug effective in targeting menopausal symptoms: News from Endocrine Conference 2017

A new class of drug Neurokinin 3 (NK3) receptor antagonists is highly effective and low risk alternative to hormone replacement therapy(HRT) for treatment of menopausal hot flashes according to a study presented at the ENDO 2017, The endocrine society annual meeting from April 1–4, 2017, in Orlando, FL.

NK3 receptor blockers fezolinetant (Ogeda) and MLE4901 (Millendo Therapeutics) were found useful in reducing moderate to severe hot flashes in postmenopausal women. 

https://obgynupdated.blogspot.com/2017/04/new-class-of-drug-effective-in.html

New natural (bioidentical) 17ß-estradiol-progesterone combination available as single soft gel capsules effective in treating postmenopausal symptoms: News from ENDO17

An innovative, investigational combination of 17ß-estradiol and progesterone in a single, oral softgel, was found effective for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. The results of the study were presented at the ENDO 2017, the annual meeting of the Endocrine Society in Orlando, Florida, April 1-4.

https://obgynupdated.blogspot.com/2017/04/new-natural-bioidentical-estrogen.html

23andMe receives FDA clearance for at home risk testing for 10 genetic diseases.

23andMe become the first ever company that receives FDA clearance for offering consumers at home genetic risk testing for 10 diseases or condition. This is the first direct-to-consumer (DTC) authorization by FDA so that people may know about their genetic predisposition to certain conditions and make lifestyle choices in consultation with health care providers.

Up Till now patients who wanted to get the genetic test done has to see a Physician to order the tests.

https://obgynupdated.blogspot.com/2017/04/23andme-receives-fda-clearance-for-at.html

North American Menopause Society (NAMS) video series about important midlife health topics: April 2017.

In this monthly series, the latest video is “treatment for perimenopause and postmenopausal bleeding” Dr. Goldstein discusses what action must be taken for spotting, staining, or bleeding for perimenopausal and postmenopausal women.

https://obgynupdated.blogspot.com/2017/04/north-american-menopause-society-nams_9.html

New natural (bioidentical) 17ß-estradiol-progesterone combination available as single soft gel capsules effective in treating postmenopausal symptoms: News from ENDO17

Courtesy: TherapeuticsMD

An innovative, investigational combination of 17ß-estradiol and progesterone in a single, oral softgel, was found effective for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. The results of the study were presented at the ENDO 2017, the annual meeting of the Endocrine Society in Orlando, Florida, April 1-4.

TherapeuticsMD, Inc which specializes in developing women’s health products has developed this combination drug named as TX-001HR. TherapeuticsMD is using the unique technology called ‘SYMBODA’ in manufacturing the softgel capsules. 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.

Robert G. Finizio, Chief Executive Officer of TherapeuticsMD. "There are currently no FDA-approved oral bio-identical estradiol and progesterone combination products for women experiencing hot flushes and night sweats. Approximately 1 million to 2.5 million women are currently estimated to use non-FDA-approved compounded menopausal hormone therapy (CBHT) in the U.S. 

TherapeuticsMD seeks to address the unmet needs of post-menopausal women as we develop potentially the first FDA-approved 17β-estradiol plus progesterone combination softgel capsule in the United States."

If the drug gets approved by FDA, it represents first single combined bioidentical estradiol and progesterone formulation in the market. Till now bioidentical hormones are custom made at compounding pharmacies which are ‘not regulated by FDA.’ Many women choose these because they think they are natural, plant based, safer and do not have any side effects.

Many Societies like The Endocrine Society, the North American Menopause Society, the American College of Obstetricians and Gynecologists (ACOG) and the British Menopause Society have all raised concern regarding the hazards of using custom-compounded hormones to treat menopausal symptoms.

The positive results of Replenish Trial, a phase 3 study that evaluated the safety and efficacy of four doses of TX-001HR were presented at the conference by Rogerio Lobo, M.D., professor of Obstetrics and Gynecology and Director of the Reproductive Endocrinology Program at Columbia University.

Replenish trial is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating four doses of TX-001HR with an objective of evaluating the drug’s effectiveness in relieving hot flashes in post-menopausal women.

The study enrolled 1835 healthy women between 40−65 years with intact uterus having ≥7/day or ≥50/week hot flushes. They were randomized to 5 groups receiving either of this 4-dose combination of TX-001HR:  E2/P 1.0 mg/100 mg; E2/P 0.5 mg/100 mg; E2/P 0.5/50; E2/P 0.25/50 or a placebo.

The efficacy of the drug was assessed by changes in number and intensity of hot flushes while on drug at end of 1 and 3 months.

Another subset of women who did not fit the criteria for VMS were randomized to receive either of the 4-dose combination of the drug to evaluate endometrial hyperplasia. All women underwent biopsy at the start of therapy and at the end of1 year. The safety end point was ≤1% incidence of endometrial hyperplasia at end of 12 months.

The results showed that TX-001HR combinations of E2/P 1.0 mg/100 mg or 0.5 mg/100 mg was most effective in controlling VMS without any unacceptable side effects.

Incidence of endometrial hyperplasia was 0%, with no reported case of endometrial cancer with any of the dose combination at the end of 12 months which is unlike reported cases of endometrial hyperplasia with compounded bio-identical hormone therapy (CBHT).

Dr Lobo concluded his talk saying “TX-001HR, "if approved," would be a new oral hormone-therapy option for postmenopausal women with moderate to severe vasomotor symptoms who have an intact uterus.

It may be a new option for the estimated millions of women currently using less regulated and unapproved compounded bioidentical hormone therapy."

The combination hormone pill Replenish Trial is the second clinical trial completed by TherapeuticsMD, which last December announced results from its Rejoice trial where it tested its softgel successfully in relieving vaginal dryness associated with menopause.

The 2 abstracts from the ENDO 17 conference can be accessed here: Abstract 1 and Abstract 2.

New class of drug effective in targeting menopausal symptoms: News from Endocrine Conference 2017.

courtesy: Getty images

A new class of drug Neurokinin 3 (NK3) receptor antagonists is highly effective and low risk alternative to hormone replacement therapy(HRT) for treatment of menopausal hot flashes according to a study presented at the ENDO 2017, The endocrine society annual meeting from April 1–4, 2017, in Orlando, FL.

NK3 receptor blockers fezolinetant (Ogeda) and MLE4901 (Millendo Therapeutics) were found useful in reducing moderate to severe hot flashes in postmenopausal women.  

The study results of MLE4901 trial were also simultaneously published in Lancet.

About two-third of women are affected by hot flashes that reduce the quality of life and overall well-being. Approximately 20 million women in the United States currently experiencing VMS. HRT is effective alternative, but it is not without any side effects and cannot be used in patients with malignancies.

In this phase2, randomized, double-blind, placebo-controlled, single-center, crossover trial 37 women aged 40–62 years were assigned to take either 40 mg BD of the drug/placebo for 4 weeks and then received other treatment for 4 weeks after a 2 weeks’ gap in between.

The primary end point of study was number of hot flashes, the secondary endpoints were hot flush severity, bother, and interference with daily activities, gonadotrophins and LH concentrations.  

MLE4901 reduced the number and severity of hot flashes considerably as compared to placebo (p<0·0001 for both). 

The women also reported increased sleep, decreased fatigue and irritability. The drug was well tolerated except a small increase in transaminase without rise in serum bilirubin.

Studies during the last 2 decades have increasingly shown the role of NKB–NK3R signaling in the etiology of menopausal hot flushes.

Dr Julia K Prague, of Imperial College London, United Kingdom, said of MLE4901 in her presentation"Treatment with the NK3 receptor antagonist could be practice-changing, as it significantly relieves hot-flash symptoms without the need for estrogen exposure. Larger-scale studies of longer duration are now indicated and planned."

The other study presented at the conference evaluated the effect of fezolinetant, which was a 12-week double-blind, placebo-controlled, multicenter study involving 80, healthy postmenopausal women between 40-65 years.

The women were randomized to receive either fezolinetant (90 mg, BID) or placebo. Women receiving the NK3 antagonist experienced 50% less frequent hot flashes that were half as severe as women in the placebo group. (P < .001)

At a biochemical level these women showed a 50% decrease in LH levels. LH levels are biomarkers for reduction in hot flashes. Quality of life, sleep and irritability also improved, that continued after stopping the drug.

Both the drugs did not have any significant effect on libido, "That is to be expected, because after all this isn't estrogen replacement," said the lead author Dr Fraser.  He further added that the safety profile is extremely good and only two patients experienced mild side effects and the patients were able to reach the end of study.

Ogeda chief scientific officer Dr Graeme L Fraser, who presented the fezolinetant data, said that the company plans to further test the drug in women who have had breast, uterine, and ovarian cancer, for whom hormone-replacement therapy is contraindicated. "This really is a perfect fit for this population, where there is an important unmet need."

Pr. Herman Depypere (UZ Ghent), principal investigator said: "More than 80% of menopausal women develop hot flashes and 20% to 30% of this population seek treatment because their symptoms are severe and debilitating and negatively affect their quality-of-life. The Women's Health Initiative Study advises against the chronic use of HRT due to important safety concerns including the increased risks of cancer and cardiovascular events. The degree of relief demonstrated with fezolinetant (a non-HRT) in this study could represent an important breakthrough in the way we can manage menopause."

The results of both these studies call for larger studies for long period of time.

The conference abstract can be accessed here.

The article in Lancet can be accessed here.