Cooling the Fire of Hormone Imbalance

XYMOGEN Introduces:

Disclaimer• The information that follows represents

XYMOGEN’s choices for presentation of studies, comments, and/or opinions.

• It is assumed that the practitioner will investigate the topic further and not use this presentation as a sole source of information from which to derive an individualized patient protocol.

Time and Money

Relief for hot flushes, a predominant symptom of menopause is among the most common reasons for clinical visits of mid-life women and a major cost in health care expenditures. The median duration of moderate to severe hot flushes was 10.2 years…The most common ages at onset of moderate-to-severe hot flushes were 45–49 years

Hot flushes are associated with:

• poor sleep

• depressed mood

• decreased quality of life

• may worsen depressive symptoms

• signal the onset or relapse of a major depressive episode

• possibly mark underlying vascular changes that are associated with subclinical cardiovascular disease

• greater incident coronary heart disease, may be a risk factor for poor bone health.

• Obstet Gynecol. 2011 May;117(5):1095-104. doi: 10.1097/AOG.0b013e318214f0de.

8-PN effects on Skin Temperature

TreatmentStarted

Treatment Ended

Menopausal Women Benefit from 8-PN

phytoestrogen preparations containing this standardized hop extract (8 PN at 100 mcg/day) may provide an interesting alternative to women seeking relief of mild vasomotor symptoms.

Heyerick A, Vervarcke S, Depypere H, Bracke M, De KD. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas. 2006 May 20;54(2):164-75.

Small Dose that isFast and Effective

Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women.Rad M, Hümpel M, Schaefer O, Schoemaker RC, Schleuning WD, Cohen AF, Burggraaf J.SourceCentre for Human Drug Research, Leiden, The Netherlands.

AbstractAIMS:Pre-clinical data suggest that the racemic phyto-oestrogen 8-prenylnaringenin (8-PN) may have beneficial effects in postmenopausal women and may become an alternative to classical hormone replacement therapy (HRT) treatment regimes. The aim of this study was to investigate the pharmacokinetics, endocrine effects and tolerability of chemically synthesized 8-PN in postmenopausal women.

METHODS:The study was performed using a randomized, double-blind, placebo-controlled, dose-escalation design with three groups of eight healthy postmenopausal women. In each group six subjects received 8-PN and two subjects placebo. 8-PN was given orally in doses of 50, 250 or 750 mg. Drug concentrations in serum, urine and faeces were measured up to 48 h and follicle-stimulating hormone/luteinizing hormone (LH) concentrations up to 24 h.

RESULTS:All treatments were well tolerated and associated with a low incidence of (drug unrelated) adverse events. Serum concentrations of free 8-PN showed rapid drug absorption and secondary peaks suggestive of marked enterohepatic recirculation. Independent of the treatment group, approximately 30% of the dose was recovered in excreta as free compound or conjugates over the 48-h observation period. The first C(max) and AUC(0-48 h) showed dose linearity with ratios of 1 : 4.5 : 13.6 (C(max)) and 1 : 5.2 : 17.1 (AUC). The750- mg dose decreased LH concentrations by 16.7% (95% confidence interval 0.5, 30.2).

CONCLUSION:Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal women. The pharmacokinetic profile of 8-PN was characterized by rapid and probably complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity. The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

PMCID: PMC1885137Free PMC Article PMID:16934044[PubMed - indexed for MEDLINE]

CONCLUSION:• Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal

women. • The pharmacokinetic profile of 8-PN was characterized by rapid and probably

complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity.

• The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

Starts changing the balance after one

dose

Don’t confuse 8-PN with

other Hops Extracts• Dr. Arne Heyerick is from the Integrated Multidisciplinary

Center for Molecular Nutrition Laboratory of Pharmacognosy and PhytochemistryFaculty of Pharmaceutical SciencesGhent University – Ugent

•  ”The mode-of-action and target applications for 8-PN vs reduced Iso-alpha-acids (RIAA) are completely different. RIAA are anti-inflammatory compounds and would work via inhibition of specific kinases in inflammatory pathways. RIAA do not have any effect on estrogen-related targets.”

• “8-PN is a phytoestrogen and interacts with estrogen-related targets to modulate estrogen-related pathways. 8-PN can exert both pro-estrogenic effects (eg. through estrogen receptor alpha and beta) and anti-estrogenic effects (eg. through aromatase) and therefore acts as an estrogen modulator rather than a pure estrogen such as estradiol.”

Hot flushes are associated with:

• poor sleep

• depressed mood

• decreased quality of life

• may worsen depressive symptoms

• signal the onset or relapse of a major depressive episode

• possibly mark underlying vascular changes that are associated with subclinical cardiovascular disease

• greater incidence of coronary heart disease

• may be a risk factor for poor bone health.• Obstet Gynecol. 2011 May;117(5):1095-104. doi:

10.1097/AOG.0b013e318214f0de.

“8-PN exerted anti-aggregatory and anti-adhesive effects on human platelets…”

“8-PN may represent a useful tool in the therapy and prevention of vascular diseases associated with platelet aggregation, such as atherosclerosis, myocardial infarction, coronary artery disease, and thrombosis.”

8-PN on CVD Progression

“These data suggest that hops extracts possess cancer chemopreventive activity through attenuation of estrogen metabolism mediated by 8-PN.”

Cancer Prevention Research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2012 Jan; Vol. 5 (1), pp. 73-81. Date of Electronic Publication: 2011 Oct 13.

8-PN and Breast Health

“Bone properties with 8-PN supplementation reached a level similar to that seen after estrogen supplementation.”

“Estrogen and 8-PN showed superior results in the analysis of bone mineral density compared to calcium...”

“Treatment with 8-PN resulted in very good biomechanical properties and showed an increased Bone Mineral Density (BMD).”

8-PN in Bone Health

Graphic: http://www.linnea-worldwide.com/downloadsarticles/hmrlignan.pdf

Flax for Hot Flashes

• In an open-label, pilot study, flaxseed (40 grams/day) was found to decrease mean hot flash scores after 6 weeks of ingestion in women with moderate to severe menopausal symptoms.

• 57% reduction in hot flashes but 50% of women experienced GI symptoms and 6 (21%) withdrew from the study.

• J Society Integrative Med 2007;5:106-12.

Hot Flashes Changes:Start: 4.5 per dayWeek 4: 2.7 per day (-37.2%)Week 8: 2.0 per day (53.5%)

8-week controlled study in 20 menopausal women (age 50-75 years.)

Presented at Scripps Integrative Medicine 5th Annual Natural Supplements Conference, January 2008

80 times more Flax for similar results on hot flashes

40 grams0.5 grams

Less is MORE with HMRlignan

Plant lignans create far reaching benefits after they have been ingested and converted by intestinal bacteria to mammalian lignans.

Secoiso-Lariciresinol

(FLAX)

Matairesinol

Hydroxymatairesinol (HMR)

EnterolactoneGut

microflora

EnterodiolGut

microflora

• In humans, 7-HMR is a direct metabolic precursor of the mammalian lignan, enterolactone (ENL).

Small doses HMRLignans significantly increase enterolactone levels in humans.*

http://www.linnea-worldwide.com/downloadsarticles/hmrlignan.pdf

This information has not been evaluated by the Food and Drug Administration. This formula is not intended to diagnose, treat, cure, or prevent any disease.

Vegetarians have high Enterolactone

Levels

In humans, HMR Lignan is a direct metabolic precursor of the mammalian

lignan, enterolactone (ENL).

Study type Group, N Result Reference

Case-control

BC diagnosedPre-mp =68Post-mp =126Controls = 208

Serum ENL significantly inversely correlated with BC risk in both pre- and post-menopausal women

Pietinen et al., Cancer Epidemiol Biom Prev 2001;10:339-44.

Case-control

BC diagnosed Pre-mp = 220Controls = 237

Premenopausal BC risk decreased with increasing plasma ENL but not genistein.

Piller, et al., Eur J Cancer Prevent 2006;15:225-32.

Cohort study

Palpable cysts, n= 258

A direct correlation between serum and cyst fluid ENL. Inverse correlation between cyst fluid ENL and EGF.

Boccardo et al., Breast Cancer Res Treat 2003;79:17-23.

Cohort study

381 cases381 controls

ER negative cancer, protection at over 20 nmol/L ENL

Olsen et al., Cancer Epidem Biom Prev 2004;13:2084-9.

Enterolactone Benefits for CVD

•Serum enterolactone (ENL) has been shown to decrease Plasma F2-isoprostane (a measure of lipid peroxidation)

• Atherosclerosis 2002;160:465–9.

•Serum enterolactone (ENL) levels are inversely correlated with risk of coronary heart disease-related and cardiovascular-disease-related mortality.

• Arch Intern Med 2003;163:1099–1104.

We have reviewed scientific evidence that appears to demonstrate that lignans and 8-PN are important for healthy

hormone balance. We have mentioned cancer, cardiovascular diseases, and anti-inflammatory activity.

•It’s important to remember that dietary supplements CANNOT mitigate diseases or replace drugs.

• However, XYMOGEN products CAN give your patients their best chance to stay healthier longer*

Estro Harmony™

*These statements have not been evaluated by the Food and Drug Administration.This product is not intended to diagnose, treat, cure, or prevent any disease.

Menopause Symptom Scores decreased in 4 weeks with

Estro Harmony†

Case Studies byDavid Haase, MD

†Case studies represent results of a single participant. Consumers should weigh these results with other scientific data and should not expect the same results as those found in case studies alone.

Estro Harmony ensures that the standardized amount of 8 PN and HMR Lignan are at clinically validated levels for optimal results.

Most hops formulations cannot make this same statement.

Clinical Applications

• Helps Protect Breast Cells*

• Relieves Normal Menopausal Symptoms*

• Hot Flashes*

• Supports Healthy Cardiovascular Status*

• Supports Bone Remodeling*

• Supports the Body’s Natural Process of Healthy

• Aromatase Activity**These statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure, or prevent any disease.