"Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women: A Randomized Trial."

FAQ Genistein

Q: What is Genistein?

A: Genistein (or aglycone genistein) is an isoflavone phytoestrogen that is abundant in certain fermented soy products (i.e. natto, miso, tempeh), and has been shown to increase bone mineral density in osteopenic postmenopausal women.

Q: Have any studies been done on genistein?

A: A study was recently published in the journal The Annals of Internal Medicine. University Hospital in Messina, Italy conducted a randomized placebo-controlled trial of 389 women aged 49 to 67 to examine the effects of 2 years' treatment with genistein on bone mineral density and bone metabolism in postmenopausal women with osteopenia. Researchers concluded that genistein increased bone mineral density at the femoral neck and lumbar spine at 24 months.

Q: How much Genistein did these women take?

A: The Messina study concluded that 54 mg genistein per day, taken in divided doses irregardless of meals, increased bone mineral density in postmenopausal osteopenic women.

Q: I eat soy. Can I get enough genistein from my diet?

A: The amount of genistein (54 mg/day) administered in this study cannot be easily obtained by a mere change of diet. Given the low amounts of aglycone genistein in most soy foods as well as supplements and low consumption of fermented soy products in the western diet, it would be extremely difficult to obtain 54 mg/day of purified genistein from food sources. Moreover, soy, soy supplements and soy food products also typically contain high levels of diadzein, which may antagonize the effects of genistein on bone. For instance, individuals would need to consume over 1 kg of the highest genistein containing foods (i.e. about 4 kg of tofu or 9 kg of soymilk) to achieve the amount of genistein aglycone (54 mg/day) administered in this study.

Q: I take estrogen HRT to help with bone mineral density. Would genistein benefit me?

A: HRT treatment of osteopenia is associated with increased risk for breast, endometrial and ovarian cancer, cardiovascular disease, and stroke. However, as a natural selective estrogen receptor (ER) modulator, genestein may positively regulate bone cell metabolism without the harmful estrogenic activity in the breast and uterus. Genistein produces effects on osteoblasts that inhibit osteoclastic activity, promotes osteoblast survival and causes direct stimulation on the anabolic effects of osteoblasts.

Q: Can I give genestein to my patients with osteoporosis?

A: Future studies in osteoporotic women are warranted to determine whether genistein also significantly decreases fracture risk in this group.

Q: Is genistein contraindicated for any patient population?

A: Genistein is not intended for pediatric patients or for pregnant or nursing women because it has not been tested in these groups. Moreover, because no studies have been done in these populations, as a precaution, aglycone genistein is contraindicated for patients with a history of cancer of the breast or reproductive organs.

©Labrix ETL/LF 2008

Article Synopsis:"Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women: A Randomized Trial." Ann Intern Med, 2007; 146(12):839-47. 45456 (9/2008).

Conclusion: In 389 osteopenic postmenopausal women genistein at 54 mg/d in divided doses irregardless of meals increased BMD at the femoral neck and lumbar spine at 24 months.

Bone mineral density (BMD) is reduced with the onset of menopause. HRT has been the hallmark treatment of osteopenia for many years, but it is associated with an increased risk of breast, endometrial, and ovarian cancer, cardiovascular disease, and stroke. Phytoestrogens, present in soy products, carry lower risk for such adverse effects and are used by many women to maintain BMD. Genistein (aglycone genistein), an isoflavone phytoestrogen that is abundant in certain fermented soy products (natto, miso, tempeh), has been shown in postmenopausal women to increase BMD at the lumbar spine and femoral neck with no adverse effects.

A recent study conducted at the University Hospital in Messina, Italy set out to explore the effects of genistein. This was a randomized placebo-controlled trial of 389 women aged 49 to 67 to examine the effects of 2 years' treatment with genistein on BMD and bone metabolism in postmenopausal women with osteopenia. Researchers concluded that genistein increased bone mineral density at the femoral neck and lumbar spine at 24 months.

Included were 389 women aged 49 to 67 years who had been postmenopausal for at least 12 months and were in good general health. Excluded were women with systemic diseases, those using hormone therapy or steroids, smokers, those with family history of estrogen-dependent cancer, and those with BMD at the femoral neck greater than 0.795 g/cm2 corresponding to a T score of -1.0 SD (i.e. osteoporosis).

After 4 weeks of stabilization with a low-soy, reduced-fat diet, women were assigned to receive either 54 mg/day of genistein in 2 tablets or identical placebo. Both genistein and placebo tablets contained calcium carbonate (500 mg) and vitamin D (400 IU). All participants were counseled to eat a reduced fat diet. The intake of soy, legumes, or other supplements was prohibited.

The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 12 and 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase
and insulin-like growth factor I, and urinary excretion of pyridinoline and deoxypyridinoline. Data on adverse events including changes in endometrial thickness were also collected.

After 24 months, Mean BMD at the femoral neck increased from 0.667 g/cm2 at baseline to 0.683 g/cm2 at 1 year and 0.702 g/cm2 at 2 years in genistein recipients. Mean BMD decreased from baseline to years 1 and 2 in placebo recipients. Similarly, mean lumbar spine BMD during 2 years increased in the genistein group and decreased in the placebo group. Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. Biochemical and liver function did not change
with time. At 2 years, genistein use was associated with reduction in the mean number of hot flashes per day vs placebo (1.7 vs 3.9 per day). More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued participating in the study.

Conclusion: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women.

©Labrix ETL/LF 2008

The Proper Collection of a Saliva Specimen

Like any laboratory test, the proper collection of a saliva specimen is vital to an accurate result. It is important for you as a provider to clearly understand the instructions enclosed in each kit so you can educate your patients or clients to ensure the best sample is submitted. The following are some frequently asked questions regarding the saliva collection instructions:

Q. Why are facial lotions or creams prohibited during collection?
A. Many "anti-aging/wrinkle" creams contain the very hormones that we test. It is easy to contaminate a specimen by direct contact with the straw or tube or by absorption into the body, thus altering the results to an inaccurate higher level.

Q. Why do all four tubes need to be submitted if only one test is ordered?
A. For the testing of Estradiol, DHEA, Progesterone, and Testosterone, we take an equal amount of specimen from each tube and transfer it into a 5th tube, the pool, which is used for testing. This process ensures a more accurate overall average of the hormone level, compensating for the natural daily peaks and troughs of these analytes. If only one tube is collected at a random time of day, there is no way to know if the result reflects one of those daily fluctuations and is accurate. For Cortisol, however, we want to catch those ups and downs, (the expected diurnal pattern) and test each tube individually.

Q. Why is there a difference in the instructions for sublingual and topical hormone use?
A. Sublingual hormones are detected in saliva for a longer period than topical hormones. If these instructions are not followed, a true therapeutic level will not be reflected.

Q. Why should cycling women collect their sample only on days 19-21 of their cycle?
A. These days should reflect the luteal phase, which is the ideal time to measure both progesterone (which should be at its peak) and estradiol in order to calculate the most accurate ratio between the two.

Q. Is it necessary to complete the symptom questionnaire on the back of the test requisition?
A. While not required, we ask that patients fill out this section so that the doctor interpreting the test results takes symptoms into consideration as well as laboratory numbers. The same thing applies to the section of the requisition where we request information on hormones the patient is taking. Please instruct your patients that we only need information about hormones, not vitamins or any other supplements.

Q. The instructions say not to eat at least one hour before collection. Does eating interfere with test results?
A. The ingestion of food is not the issue; it is the creation of as "clean" a specimen as possible. Food can create a more viscous or "junky" specimen and any particles can interfere with the testing process. While there are laboratory procedures to eliminate as much of this type of interference as possible, it is best to submit a sample taken when food residue is not in the mouth.

Understanding the importance of collecting a good sample is the first step to achieving the accurate and reliable results that have helped us set the standard for salivary testing!

Labrix Billing and Operational Procedures

By now you should have a pretty good idea of how to administer a test kit, access and interpret results, and provide a general treatment protocol. Now comes the business side of building a successful saliva testing program into your already successful practice. In this newsletter we have identified a number of frequently asked questions related to the business of saliva testing with Labrix.

General Billing Issues

What billing options are available through Labrix?

I. Direct Collection: Receive the wholesale price and collect payment from your patient directly.

II. Labrix Collection: We will collect the fees for testing and bill insurance if applicable; please contact Labrix for retail and insurance rates.

Please Note: You will need to choose Option I or Option II. A combination of the two options is not available at this time.

Do my patients have to pay up front for this testing?
No, when you elect to have Labrix collect, and your patients want their insurance billed first, we will do so (except for Blue Cross, which we require payment in advance). We will then bill your patients for the remaining balance should there be one.

Does insurance cover this?
If a person's policy covers hormone testing, then our FDA-approved testing will be covered under their insurance.

Can I do direct collections for some patients and have Labrix bill insurance for others?
You will need to choose to be a direct collections vendor (wholesale price, you collect testing fees) OR a Labrix collections vendor (we collect for testing as stated above).

Does Insurance billing affect my results turn-around-time?
Absolutely not! You will receive results guaranteed in 3-5 business days with either option. This is a standard part of Labrix's commitment to customer service.

How often does Labrix bill my account?
For Option 1, Direct Collections, Labrix will bill you the first week of the following month, for all test completed the prior month.

Will I receive an itemized invoice with what patients Labrix is billing for?
Yes! You will always be mailed a copy of your bill and an itemized list of patients tested for the specific month, as well as the date and what was tested.

What happens if Labrix normally charges my credit card, and instead I receive an invoice stating I owe?
Most likely your credit card did not authorize the charge due to expired credit card, not sufficient funds, canceled card, etc...Please be sure to contact the Lab with updated payment information to ensure finance charges are not applied.

Is it legal to mark up testing?
This depends on the state in which you do business. Please refer to your states rules and statutes.

What is the most common retail pricing for testing?
Please contact Labrix for suggested retail pricing.

Insurance Questions

Will Labrix bill insurance for my patients?
Labrix will bill Medicare for any of your applicable patients, however you must choose Option 2: Labrix Collections, in order for Labrix to bill private insurance.

What forms are required to bill insurance?
Please call the Lab and we can provide the appropriate forms. These are required to file insurance claims.

Are there different pricing schedules for insurance billing?
When Labrix bills insurance the patient is responsible for any amounts not paid by the insurance company (an exception is with Medicare: patient is not responsible for remaining balance unless the claim was denied by Medicare. In that case they will be responsible for the full amount).

Will the patient receive the reimbursement or will the Lab?
Most insurance companies will reimburse the Lab, however BlueCross BlueShield sends the check to the patient. Please be sure to notify these patients that the amount should be submitted in advance (with the specimen), or their sample will not be processed.

What if the patient has insurance questions?
If you have signed up for Option 2: Labrix Collections, the patient can call our office for insurance questions.

Operation Issues

Does Labrix provide the private labeling of test kits and reports?
For customers with significant monthly kit volumes and the desire to apply their brand to all elements of the testing process (kits, requisition forms, reports, etc...) Labrix offers a private label program. Call us for more information.

What are the most common profiles that are ordered through Labrix?
The most common profile ordered at Labrix is the Basic Hormone Panel (5-hormones). This includes Progesterone, Testosterone, DHEA and the AM Cortisol. This is a great baseline for starting a hormone monitoring program. You can always call within 30 days of the Lab receiving the sample to order the additional Cortisols for testing if needed.

How do we order more kits?
Simply call the Lab at 877-656-9596 and let us know how many kits you need.

Who pays for shipping?
Labrix pays for all ground shipping, however if you need the kits faster then ground, we will simply invoice you for the difference.

What if we want to guarantee quicker shipping to the Lab?
Labrix has an arrangement with UPS for guaranteed 5-business day delivery. Call the Lab to learn more about this shipping option and the additional cost.

Does Labrix offer assistance in building a world class saliva testing program?
Of course! We are always very excited to help our customers build a state of the art program into their practice. Call Labrix to discuss your needs and objectives.

Does Labrix offer a Drop Ship Program?
If you require individual shipping of kits to your patients directly, Labrix offers a simple drop ship program. Call the Lab for more details.

Does Labrix work with customers outside of the USA?
Labrix has customers all over the world. Are you interested in doing business outside of the US or know an international health care provider looking for excellent saliva testing service? Call the Lab today to learn more about our International Programs.

Does Labrix work directly with patients?
Labrix prides itself on the fact that we work with and therefore do not compete with the health care provider. We refer all questions and inquiries back to the health care provider (unless it is a billing/insurance question under Option 2: Labrix Collection program).

Copyright 2008 Labrix Clinical Services, Inc.

Bioidentical Hormones Supplementation Guidelines

These guidelines are provided based upon 26+ years of combined
experience balancing women and men's sex hormones.

INTRODUCTION: We have found the dosages, intervals and applications to be excellent starting points once a need for supplementation has been established clinically and through laboratory validation.

Please note that these are starting dosages, which need to be monitored through laboratory and clinical follow-up. We routinely test saliva for baseline hormone levels prior to initiating supplementation with repeat laboratory testing and clinical follow-up at 2 months intervals until hormones are balanced; then yearly thereafter.

PROGESTERONE

Pre-menopause interested in conception: USP Progesterone 20-30mg in a trans-dermal base (e.g. Vanpen) applied day 15 thru 28 of the menstrual cycle. Rotate application daily to the "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Dose may be given qd or split into bid application as preferred by provider and patient. An example script: P4 25mg/ml, #30, Sig: ½ml bid or 1ml qd (day 15 thru 20). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Pre-menopause NOT interested in conception: USP Progesterone 20-30mg in a trans-dermal base (e.g. Vanpen) applied day 7 thru 28 of the menstrual cycle. In other words, this means apply on days not menstruating. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. An example script: P4 25mg/ml, #30, Sig: ½ml bid or 1ml qd(day 7 thru 28). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Post-menopause: USP Progesterone 20-30mg in a trans-dermal base(e.g. Vanpen) applied daily. Some providers prefer to cycle dosage, e.g., 3 weeks on and 1 week off. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: P4 25mg/ml, #30, Sig: ½ ml bid or qd or alternatively: Sig: ½ ml bid or 1ml qd (3 wks on, 1wk off). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Andropause (Men): USP Progesterone 5 to 10 mg in a trans-dermal base (e.g. Vanpen) applied daily. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example script: P4 10mg/ml, #30, Sig: ½ml qd.You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

BI-ESTROGEN (BIEST)

Pre-menopause interested in conception: USP Estriol(E3) and estradiol(E2) combination: 1mg (E3:E2;4:1) in a trans-dermal base (e.g. Vanpen) applied day 1 thru 13 of the menstrual cycle. Rotate application daily to the "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Dose may be given qd or split into bid application as preferred by provider and patient. An example script: Biest 1mg (E3:E2;4:1)/ml, #30, Sig: ½ml bid or 1ml qd (day 1 thru 13). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Pre-menopause NOT interested in conception: USP Estriol(E3) and estradiol(E2) combination: 1mg (E3:E2;4:1) in a trans-dermal base (e.g. Vanpen) applied day 1 thru 25 of the menstrual cycle. Rotate application daily to the "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Dose may be given qd or split into bid application as preferred by provider and patient. An example script: Biest 1mg (E3:E2;4:1)/ml, #30, Sig: ½ml bid or 1ml qd (day 1 thru 25). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Post-menopause: USP Estriol(E3) and estradiol(E2) combination: 1mg (E3:E2;4:1) in a trans-dermal base (e.g. Vanpen) applied daily. Some providers prefer to cycle dosage, e.g., 3 weeks on and weeks off. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: Biest 1mg (E3:E2;4:1), #30, Sig: ½ml bid or 1ml gd or alternatively: Sig: ½ml bid or 1ml gd (3 wks on, 1wk off). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

TESTOSTERONE

Women: USP testosterone: 0.5 to 1.5mg in a trans-dermal base (e.g. Vanpen) applied daily. Some providers prefer to cycle dosage, e.g., 3 weeks on and weeks off. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: Testosterone 0.5mg/ml, #30, Sig: ½ml bid or 1ml qd or alternatively: Sig: ½ml bid or 1ml qd (3 wks on, 1wk off). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Men: USP testosterone: 10 mg in a trans-dermal base (e.g. Vanpen)applied daily. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: Testosterone 10mg/ml, #30, Sig: ½ml bid or 1ml qd. You may want to give 2 refills, which will take the patient up to the 2 month retest interval. Note: It is important to monitor PSA and CBC levels during the treatment interval.

DHEA

Women: USP DHEA: 10mg in a trans-dermal base (e.g. Vanpen) applied daily. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: DHEA 10mg/ml, #30, Sig: ½ml bid or 1ml qd. You may want to give 2 refills, which will take the patient up to the 2 month retest interval. Note: DHEA supplementation will often raise testosterone levels (conversion in the adrenal glands), which may alleviate the need for testosterone supplementation.

Men: USP DHEA: 10 mg in a trans-dermal base (e.g. Vanpen) applied daily. Rotate application daily to a "thin" region of the body: inner wrist, behind knees, upper inner arm or upper chest. Example scripts: DHEA 10mg/ml, #30, Sig: ½ml bid or 1ml qd. You may want to give 2 refills, which will take the patient up to the 2 month retest interval. Note: DHEA supplementation in males will NOT raise testosterone levels.

COMBINATION FORMULAS

All bio-identical hormones can be combined effectively into a single trans-dermal cream. Though while finding the correct balance, it may be advantageous to prescribe the hormones individually. Conversely, once combined into a single cream the absorption characteristics of each hormone may change slightly. Providers tend to be split evenly on which approach is best--as are we. You will have to find the approach that best suits you and your patients. The following combination examples have been found by each of us to effectively correct hormone imbalances:

Post-menopause: Biest 1mg (E3:E2;4:1), P4 25mg, DHEA 10mg, testosterone 0.5mg, #30, Sig: ½ml bid or 1ml qd or alternatively:Sig: ½ml bid or 1ml qd (3 wks on, 1wk off). You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Men: P4 5mg, testosterone 10mg, DHEA 10mg/ml, #30, Sig: ½ml bid or 1ml qd. You may want to give 2 refills, which will take the patient up to the 2 month retest interval.

Copyright 2008 Labrix Clinical Services, Inc.

Iodine FAQ’s:

I’ve heard that the Iodine skin test works just as well as the Iodine Spot and Load Urine test for determining whether I’m deficient in Iodine. Is that true?

No, the skin test will not accurately assess your body’s tissue stores of Iodine. The skin test will only reflect your local absorption of liquid iodine at that site. And since 88 % of the Iodine applied to the skin will evaporate you are only absorbing 12 percent of the applied iodine.

Additionally, this Iodine evaporation increases with increased ambient temperatures and decreased atmospheric pressure, so depending on whether you are in Colorado or California you may have a substantial difference in skin patch results.

It is also of note that the yellow color of iodine will disappear when reduced to iodide by the skin since iodide is white. So it is thought that this is not so much a reflection of Iodine deficiency (when the yellow color leaves) but the expected conversion to the iodide (white) form.

In conclusion, the skin test is not an effective means for evaluating iodine deficiency. Guy Abrahams MD concisely summarizes it thusly: “…the iodine patch test is not a reliable method to assess whole body insufficiency for iodine. Many factors play a role in the disappearance of the yellow color of iodine from the surface of the skin…the iodine/iodide loading test is much more accurate”.

The Bioavailability of Iodine Applied to the Skin, Guy E Abraham MD, The Original Internist June 2008

©Labrix Clinical Services ETL2008

$20.00 Off Testing Promotion with the Purchase of Slim, Sane, and Sexy

Labrix has teamed with Calaroga Publishing to offer $20.00 off of a Comprehensive Hormone Analysis with the purchase of EVERY Slim, Sane and Sexy book. Purchase the books at wholesale and resell them and your patients get a $20 off coupon to purchase a Labrix 8-panel Hormone Test at your location.

This means if you are selling the Labrix book at the retail price of $19.95, the book is essentially free to the customer when they then go on to purchase their Labrix 8-panel Hormone Analysis from your business. It’s a win-win for everybody! The customer is taking action and responsibility for their health, and you are providing them with the tools for which they start their BHRT journey!

Start carrying Slim, Sane, and Sexy today! To order wholesale please click here to download the wholesale pricing and order form!

The process is straightforward:.

1. The customer will provide your business with one-half of the coupon “provider” and if you chose to participate you provide them $20.00 off of their Labrix Comprehensive 8-panel saliva hormone test kit.

2. The customer will then place the other half of the coupon “lab” in the test kit when sending the samples back to Labrix. This step is important because it is what signals to the lab that you provided the customer with $20.00 off on your end. You may want to put the coupon in the kit box & explain the process.

3. We will then credit your account with $20.00 for each coupon that arrives in a test kit.

Want to sell more kits? Order Slim, Sane, Sexy at wholesale prices and resell them at your location…remember each book comes with the $20.00 off coupon!

Please Note: Whereas all books come with the coupon, you are by no means required to offer your customers the discount, even as crazy as that might be!

Wholesale Pricing and Order Form

Labrix is excited to introduce our new National Sales and Marketing Director

We are delighted to announce that Kate Wells has recently joined the Labrix team as our National Sales and Marketing Director. Kate has over 20 years experience in all aspects of business operations including several years' prior experience in the diagnostic hormone testing field.

From a start in retail banking marketing, through organizational development, to operations management and sales, Kate is bringing to us years of hands on experience plus a systemic approach to every element of the work within the company. Balancing a capacity to focus in on detail and ensure accuracy, with the ability and desire to see each area of the business in an interwoven broader concept Kate will add depth and breadth to marketing and sales process in our fast growing and very nimble company. She is skillful at swiftly developing process which supports and develops an organizations' capacity to serve its customers in a timely and effective way, and she is passionate about providing educational resources for providers and their patients.

As National Sales and Marketing Director Kate will be someone you meet often at conferences; she will be someone you can contact with any questions about the operation of your account; she and her department will be a resource for you and your staff as you grow your testing program. Kate brings a drive and determination to produce high quality services on a consistent basis and is ready to answer your questions and support the growth of your practice both for your patients and your bottom line.

When she manages to pull herself away from work…Kate is an active outdoors woman and, with her two teenage daughters, enjoys many activities available in the Pacific Northwest...particularly those that involve mountains and water. Kate is the first person to say that finding balance can be a challenge…but she tries to set the example at all times by laughing often, enjoying life to the full and, of course, by testing regularly!

Please join us in welcoming Kate to our team. She can be reached at 503-342-8367 ext 1367 and kate.wells@labrix.com with your questions and suggestions.