Improvement of climacteric symptoms

with a novel sublingual product,

TALITHA, containing trans-Resveratrol

Investigator:
Dott.ssa Roberta Milia
Specialised in Obstetrics & Gynecology
Monza (Italy)

Presented at:
23rd International Scientific Conference of
Obstetrical and Gynaecological Society of Bangladesh,
Dhaka, Bangladesh, September 25 27, 2014

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Fig. 1 The Menopause Rating Scale mean total score was 18.3 (SD: 6.2) at baseline.
By three months, a reduction was observed in all patients, with a mean value of 7.4
(SD: 4.5).

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Hot flushes mean score

Fig. 2 The hot flushes mean score was 2.20 (SD: 1.12) at baseline. By three months,
a reduction was observed in all patients, with a mean value of 0.57 (SD: 0.86).

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Results
Menopause Rating Scale total score - This reduction was statistically significant at the 0.05 level (Figure 1). Moreover, a statistically significant difference was also
observed with a significance level of 0.01.
Hot flushes total score - This reduction was statistically significant at the 0.05 level (Figure 2). Moreover, a statistically significant difference was also observed with a
significance level of 0.01.
MTS Single items mean total score - Other than hot flashes, also the following items showed a statistically significant reduction (p<0.05) (Figure 3): Heart discomfort;
Sleep problems; Depression mood; Irritability; Physical and mental discomfort; Joint and muscular discomfort. Moreover no patient experienced any side effects
and compliance was optimal.

Objectives: study the amount of improvement of climacteric symptoms, especially hot flushes, evaluated analyzing the total score of Menopause Rating Scale at baseline and after
administration of TALITHA. Materials and Methods: 30 women with symptoms suggestive of climacteric syndrome present for at least one month, with or without associated amenorrhea, and evaluated according to the standardized Menopause Rating Scale (MRS)(1) were enrolled in an open, uncontrolled study. TALITHA Sublingual Spray was administered: 4-5
puffs 2 times/day for 3 months. The scoring system is straightforward: the score increases point by point with increasing severity of subjectively perceived complaints in each of the 11
items (severity expressed from 0 to 4 points in each item).

Improvement of climacteric symptoms with a novel sublingual product, TALITHA, containing trans-Resveratrol

Fig. 3 MRS single items total score: changing from baseline to the end of use.

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Potthoff P, Heinemann LAJ, Schneider HPG, Rosemeier HP, Hauser GA. Menopause-Rating Skala (MRS): Methodische Standardisierung in der deutschen Bevlkerung. Zentralbl Gynakol 2000; 122:280-286.
Barry D. Gehm, Joanne M. McAndrews, Pei-Yu Chien, J. Larry Jameson. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc. Natl. Acad. Sci. USA Vol. 94, pp. 1413814143, December 1997.
Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:9-15.

Conclusions: The results of this study, despite the small sample size, show that TALITHA, a novel trans-Resveratrol-based Sublingual Spray, produces a statistically significant reduction of the main symptoms associated with menopause when measured with a validated method.

Discussion: Resveratrol is a powerful phytoestrogen(2). that can be used as an alternative to hormone replacement therapy. Because of its mechanism of action, it is considered particularly useful to tackle many of the derangements associated with climacteric syndrome, including vasomotor symptoms. TALITHA is formulated as a sublingual spray emulsion, by which
resveratrol is rapidly absorbed through the sublingual mucosa reaching the systemic circulation, without being metabolized and thus inactivated by the liver, as it happens with the
conventional oral preparation(3).

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Clinical study highlights

The cessation of ovarian function at the time of menopause and resulting hormonal changes, mainly estrogens
deficiency, are associated with specific health conditions that may lead to quality of life impairment, especially
hot flushes and night sweats, that may also be associated with sleep and mood disturbances, as well as vaginal
epithelium atrophy and decreased cognitive function.
These symptoms had been primarily managed with long-term hormone replacement therapy that has been
demonstrated to cause serious adverse effects including stroke, gallbladder disease, as well as endometrial, uterine
and breast cancers.
Products containing natural estrogens, or phytoestrogens, that are functionally and structurally similar to steroidal
estrogens in the body, such as estradiol, provide most of the benefits in addressing climacteric syndrome including
vasomotor symptoms and postmenopausal health risks, as well as bone formation promoting properties, without side
effects.
Resveratrol and trans-Resveratrol are powerful phytoestrogens, present in the skins of grapes and in other plant
like Polygonum cuspidatum. The bioavailability of Resveratrol administered by oral route is essentially zero as it is
metabolized by the liver and small intestine in other substances before reaching the bloodstream.
For this reason, a sublingual formulation of trans-Resveratrol, (TALITHA), able to bypass gastro-enteric tract entering directly the systemic circulation has been developed.
TALITHA is a sublingual spray emulsion containing: trans-Resveratrol, Vitamin E (powerful antioxidant) and Vitamin D3 (essential for normal bone formation).
A clinical study on 30 women with climacteric syndrome symptoms present for at least one month, with or without
associated amenorrhea, was conducted to establish the usefulness of TALITHA administered for 3 months (4-5
puffs 2 times / day) in terms of:
improving climacteric symptoms, especially hot flushes, evaluated by mean of the validated Menopause Rating Scale
(MRS);
recording the occurrence of any adverse event.
The MRS is a scoring system in which the severity of each of the subjectively perceived 11 symptoms (hot flushes, sweating;
heart discomfort; sleep problems; depressive mood; irritability; anxiety; physical and mental exhaustion; sexual problems;
bladder problems; dryness of vagina; joint and muscular discomfort) is expressed with a 0 to 4 increasing score.
In all patients after three months of administration the following were observed:
a reduction of severity of hot flushes/sweating, the most disabling symptoms: the item hot flushes showed a
statistically significant reduction (p<0.01) demonstrating that TALITHA statistically reduces hot flushes and
episodes of sweating;
an improvement of all the climacteric symptoms: the Menopause Rating Scale mean total score showed a statistically significant reduction (p<0.01). TALITHA was particularly useful in improving the following symptoms
(p<0.01):
heart discomfort (unusual awareness of heart beat, heart skipping, heart racing, tightness)
sleep problems (difficulty in falling asleep, difficulty in sleeping through, waking up early
depression mood (feeling down, sad, on the verge of tears, lack of drive, mood swings)
irritability (feeling nervous, inner tension, feeling aggressive)
physical and mental exhaustion (general decrease in performance, impaired memory, decrease in concentration,
forgetfulness)
joint and muscular discomfort (pain in the joints, rheumatoid complaints)
No adverse events were registered.
The results showed that TALITHA, a novel trans-Resveratrol-based Sublingual Spray, is able to statistically
reduce both hot flushes and sweating, the most disabling symptoms, as well as the other main symptoms
associated with menopause.