Hormone Replacement Insights from Jim

What's the Word? Part 1: BHRT Terminology

2011-05-09T11:09:00.000-07:00

When is natural really natural?

Terms used to describe the use of bioidentical hormone therapies can be misleading and misunderstood when the words have different meanings to different parties. The most common problem area lies with the use of the word "natural." Natural to the majority of lay people means that the substance exists in or comes from nature. The usual perception is that if a substance is natural, it is generally safer for consumption than the alternative, something synthetic, or made in a laboratory. While it is true that most natural herbs and botanicals have less adverse side effects than counterpart pharmaceutical drugs, just because it comes from nature doesn’t make it totally safe. Natural substances can have side effects, and some substances from nature are poisonous to humans.

To me, natural should refer to the system that the substance is used in, not where it came from. To be considered natural to the human body, the substance needs to be something we would consume in our normal diet, or it matches what the body normally produces.

Just because something originates from nature, it doesn’t make it natural for human beings. For marketing purposes, Conjugated Equine Estrogen has been described in some publications as natural because the source is found in nature. But it’s not natural for a horse to consume its own urine, much less to put it into a human. What makes a hormone natural for us is that the chemical or molecular structure is exactly identical to that which the body has produced itself for years. That is why I much prefer the term bio-identical, meaning identical to the structure produced by our own biological system.

Bioidentical hormones are natural in the sense that they do originate in nature. A precursor chemical found in soy and yam plants is extracted, and then converted in a lab to the exact structure of the hormones produced by our body. In a sense, since the precursors are converted in a laboratory, they could be considered semi-synthetic and not totally natural. However, since they match the hormones that our bodies produce, they are in fact 100% bio-identical. In matching the molecules produced by our bodies with bioidentical hormones, we are attempting to match the same functions of the hormones that they have preformed for years in our bodies, which is the key to safer, effective hormone therapy.

Phytoestrogens are natural substances that are often used to treat the symptoms of menopause. While they may help to relieve bothersome symptoms such as hot flashes and insomnia, they do not duplicate all the actions of the hormones in our bodies. Phytoestrogens have not been shown to provide the same cardiovascular, bone, or brain protection that our own hormones do. While useful as an adjunctive therapy to help with symptom management, phytoestrogens should not be relied on to replace deficient estrogen in providing protection to multiple critical systems.

Many times I hear the word “conventional” used to describe hormone therapy. There are conventional therapies that use bio-identical hormones and conventional therapies that use synthetics – agents which differ in structure from human hormones. Even when conventional therapies use products that contain bioidentical hormones, in almost all cases the manufactured products deliver much more hormone than body needs or ever produced on its own. I try to avoid the use of the terms conventional and natural, and identify the therapy I use as physiological bioidentical. Physiological refers to restoring the hormone to the level of a younger individual and no more, so it separates the individualization of compounded bioidentical therapy from the one-size-fits-all overdosing mentality of manufactured bioidentical products.

ZRT Laboratory Included in At-Home Testing Study from John Hopkins

2011-05-03T14:08:00.000-07:00

A recent study conducted by the Department of Gynecology and Obstetrics at John Hopkins Medical Institutions in Maryland, includes ZRT Laboratory saliva testing and ZRT internal research data in their examination of remote testing options.

In the study, published in the May 2011 issue of Fertility and Sterility, investigators review and describe various over-the-counter testing products available to infertility patients. Drs. Brezina, Wallach and Habel conclude that at-home testing represents an opportunity for physicians to involve patients actively in their care. “When properly used, these tests also may result in cost savings. Many of the technologies used are innovative and, with proper evaluation and implementation, could serve as valuable adjuncts to medical practices,“ the study observes.

The article examines ZRT Laboratory salivary test kits, which measure a wide variety of hormones including estradiol, progesterone, testosterone, DHEA, and cortisol. Consumers, after submitting the sample, are provided with results and interpretations as to what the values mean with regard to their health. The authors mention accuracy and the ease of use as the advantage of ZRT saliva testing. ZRT Laboratory provided the investigators with internal data that support the accuracy of the laboratory in determining salivary hormone levels.

Q & A on adrenal fatigue

2011-04-20T10:18:00.000-07:00

Q: What is adrenal fatigue and how is it tested?

A: Many people today suffer from the adrenal glands' inability to respond to stress. This condition stems from various factors including chronic stress, sleep deprivation, excess caffeine and carbohydrates, chronic pain, extreme exercise, and a generally unbalanced lifestyle. Also known as adrenal insufficiency, the problem shows up with a set of symptoms ranging from chronic fatigue to infertility. Those with a hectic lifestyle are potentially at risk, but the problem is more prevalent among medical professionals, police officers, executives, teachers, single working parents, or anyone who has a very stressful lifestyle.

Adrenal fatigue is tested by measuring cortisol, a key stress response hormone. Cortisol is produced by the adrenal glands 24 hours a day, although output varies at different times throughout the day. Cortisol output is highest upon waking to energize us for the day ahead and declines steadily throughout the day, reaching its lowest point at night in preparation for sleep. Individuals with adrenal fatigue have a flattened cortisol profile. This means that there is no morning surge of the hormone. Cortisol can be collected once in the morning or twice a day (morning and bedtime). It may be necessary to measure cortisol four times a day if levels are out of range and symptoms indicate the need to test adrenal function throughout the day. For more information, call ZRT Laboratory 24-hour Hormone Hotline at 503-466-9166 and listen to Track 636.

ZRT Lab Saliva Testing Highlighted on Dr. Oz's Show

2011-04-12T17:40:00.000-07:00

On his April 11th show, Dr. Mehmet Oz, Professor of Surgery at Columbia University, talked about stress in America and highlighted ZRT Laboratory saliva cortisol testing. Watch the video.

Q&A on Hormones with Jim

2011-04-07T15:28:00.001-07:00

Q: What is the link between polycystic ovaries and hormonal imbalance?
A: Polycystic ovaries occur when numerous growths/cysts develop on the ovaries. This is commonly associated with a hormonal imbalance such as estrogen dominance and/or an excess of male hormones. In many cases, these cysts are benign and can shrink or even disappear when the hormone imbalance is corrected. The ovaries should be removed if the cysts are cancerous or causing pain and do not respond to treatment. For more information, call ZRT Laboratory 24-hour Hormone Hotline at 503-466-9166 and listen to Track 639.

Q: What is the link between uterine fibroids and hormonal imbalance?
A: Estrogen dominance, an imbalance caused by excess estrogen in the relative absence of progesterone, can cause the uterine lining to grow undetected. This can lead to the growth of tough, fibrous, non-cancerous lumps called fibroids. While the average fibroid is an undetectable lump in the wall of the uterus, about the size of a hen’s egg, larger fibroids often cause irregular bleeding and heavy or painful periods. Fibroids are the most common physical reason for excessive bleeding during menstruation.

Fibroids can grow dramatically during perimenopause when they are stimulated by hormonal imbalances and fluctuations in the body. Large fibroids secrete estradiol, the most potent form of estrogen, leading to estrogen dominance. Monitoring your estrogen levels through routine hormone testing and taking appropriate steps to maintain a proper balance of estrogen to progesterone is especially important. Please note: recent information cautions against the use of progesterone for the treatment of larger fibroids. With all fibroids, hormone supplementation should be kept as low as possible. For more information, call ZRT Laboratory 24-Hour Hormone Hotline at 503-466-9166 and listen to Track 643.

Q: What is the link between hormonal imbalance and breast cancer?
A: There are many factors associated with hormonal imbalance and increased risk of breast cancer including:

Declining levels of progesterone with age and/or with removal of the ovaries in hysterectomy
Environmental, “xeno”-hormones in the form of pollutants and pesticides
Oral contraceptives
Synthetic hormone replacement therapy

These factors can contribute to an excess of estrogen in the body known as “estrogen dominance.” Since estrogen stimulates cell growth, a predominance of it, especially in the absence of adequate levels of progesterone (common in the menopausal years with the waning of ovulation), presents an increased risk of cancer, particularly in the breast. For more information, call ZRT Laboratory 24-hour Hormone Hotline at 503-466-9166 and listen to Tapes 631 and 646.

The Myths and Truths About Iodine and Radiation Protection

2011-04-07T15:25:00.000-07:00

Listen to David Zava, PhD, ZRT Laboratory President, interview with Dr. Sherrill Sellman on Women's Healing Circle, Progressive Radio Network, on The Myths and Truths About Iodine and Radiation Protection, 03/20/2011. Click here for the interview.

Q & A on Hormone Testing

2011-03-21T08:22:00.000-07:00

Q: Where do I begin to determine whether my hormones are balanced?

A: To get a general idea of whether or not your hormones are balanced, record the symptoms you are currently experiencing using ZRT Laboratory Symptom Assessment Checklist. Your symptoms may point to a deficiency or excess of certain hormones.

Q: My symptoms suggest that I have a hormone imbalance, but how do I find out for sure?

A: To confirm your symptoms of hormonal imbalance, I recommend measuring those hormones associated with the symptoms you noted using our Symptom Assessment Checklist or on the test kit requisition form. You might consider ordering our Female/Male Saliva Profile I that tests estradiol, progesterone, testosterone, DHEA-S and AM cortisol. This panel, along with the more comprehensive Female/Male Saliva Profile II and Female/Male Saliva Profile III, provide you with a broader picture of your present hormone levels and identify specific imbalances. For the most comprehensive assessment of hormonal imbalance, including tests for reproductive, adrenal, and thyroid hormone testing, consider ordering one of our Comprehensive Profiles.

Q: How accurate is saliva testing compared to blood and urine testing?

A: Saliva testing has been used in scientific testing for decades and has been shown to be highly accurate. It is the most reliable way to measure free, bioavailable hormone activity — those hormones actually doing their job at the cell level. Standard blood and urine tests do not measure bioavailable hormone levels. Numerous scientific studies have shown a strong correlation between the levels of steroid hormones in the blood stream and the bio-available levels of steroid hormones in saliva. The World Health Organization has used this method of hormone testing in worldwide comparisons of hormone levels among women living in industrialized vs. non-industrialized countries. In addition, saliva hormone testing more accurately reflects tissue uptake and response of hormones delivered through the skin in creams, gels, or patches than blood or urine tests.

Your Spit May Hold Key to Predicting Burnout

2011-02-24T09:48:00.000-08:00

By Wallace Immen
from CTV News
2/22/2011

Go ahead: Spit if you feel frustrated about your job. What your saliva reveals could alert doctors to whether you’re at risk of burnout at work, according to new Canadian research.

And testing saliva could also help people with symptoms of burnout avoid being put on medication that might actually make the condition worse, said Robert-Paul Juster, a doctoral student at McGill University in Montreal who helped design the research.

A clue that someone is suffering burnout is lowered levels of cortisol, often referred to as the “stress hormone” because it is secreted when we feel anxious or agitated. But if we are under continual stress, our bodies can shut down production of the hormone rather than try to keep up with the constant demand.

“We wanted to … find a simple way to find low levels of the hormone showing up in people who have not yet had problems, and how that may predict risk of burnout,” Mr. Juster said.

Normally, cortisol tends to spike in the morning as people wake up, which is the body’s way of revving up after a night’s sleep. Levels usually decline during the day. “But we find that people with high stress don’t have that boost of cortisol in the morning,” Mr. Juster said. “They report feeling exhausted in the morning, even though they’ve had a full night’s sleep.”

Burnout, clinical depression, or anxiety-related issues in the workplace affect at least 10 per cent of North Americans and Europeans, according to estimates prepared by the International Labour Organization.

Read more ...

Insurance Based Testing

2011-02-15T10:54:00.000-08:00

Many insurance companies have denied coverage for saliva testing for hormones stating that it is an unproven experimental procedure which lacks scientific validation. In doing so, they ignore the hundreds of published articles which provide good evidence that saliva testing is indeed a convenient and useful method for testing hormones.

In my opinion, the insurance billing companies have denied coverage for saliva testing in hopes that the patient will choose to pay for the tests and they will not have to pay a claim. As the benefits of saliva testing on overall health continue to be demonstrated, some insurance companies have now started to cover this type of testing. These progressive companies understand that physiologic hormone balance is critical to helping prevent many disease states associated with aging. They also recognize the fact that saliva testing is much less expensive than conventional venous serum testing.

Are there any effective ways to get insurance coverage for saliva testing?
There are several methods that can be attempted, but the easiest and most successful is for the practitioner to establish a cash-based practice. Many patients understand the issues with insurance and are willing to pay for what they view as good health care. There are numerous practitioners that have changed to a cash-based practice, and the vast majority is successful and extremely satisfied with the change.

However, the other side of the picture is that the patient is still not receiving insurance coverage for a beneficial testing procedure that is saving the insurance company money in the long term. That is why, I have addressed the issue through other methods at times.

When in practice, I helped patients create a letter to use in their struggle to get saliva testing reimbursed. I inform the patient that in many cases they are dealing with the billing company hired by the insurance company to handle claims, and that the main objective of an insurance billing company is too keep down claim costs. That’s why it may be more beneficial to include copies of all correspondence to the actual insurance company and the health benefit provider at the patient’s employer.

The letter offers to supply numerous published articles that show the effectiveness and usefulness of saliva testing, and inquires if they have reviewed these articles when stating that saliva testing is unproven and experimental. At the same time, the letter asks the insurance company for studies that validate conventional venous serum testing with the administration of topical hormones, a procedure commonly covered as an acceptable way to measure hormone need.

The letter also requests that the insurance company explain why it would deny coverage for a testing procedure that the practitioner considers accurate, that the patient desires, and that is typically 1/4 to 1/3 the cost of covered conventional testing. Do they consider themselves a better judge of effectiveness and usefulness of testing than a trained medical professional?

Finally, the letter solicits that the insurance company reconsider and provide coverage immediately, so that the patient does not have to pursue other avenues of making their point. The letter also states that the patient is willing to present his/her side of the issue to the State Insurance Department Ombudsman’s Office, local and state legislators, the board of directors for the insurance company, and the local media if necessary. I suggest that the patient provide the names and addressed for all the above to indicate he/she is serious in the pursuit to obtain fair coverage.

Insurance billing companies generally do not wish to have to deal with ombudsmen, media or legislative representatives, so the letter has been successful in several cases.

What if the letter does not change the insurance companies’ stance?
If all else fails, the ordering practitioner can greatly assist the patient in getting reimbursement by providing a letter to the insurance billing company. In such a letter, the practitioner would state they have looked at the scientific studies and determined that saliva testing is indeed a valid method of measuring hormones. The practitioner should also relate their personal experience at clinical success in using saliva testing. The huge cost savings should be included as a factor in the practitioner choosing this method of testing.

Finally, a practitioner I know once wrote a letter stating that she would be using saliva testing for her patient because her training, research and clinical experience indicates it is a valid choice, and her preferred method of testing. She also declared that if the insurance company failed to cover the expense, she would also be testing the patient by conventional serum testing, so the insurance company would still be paying a claim. It would be their choice as to whether they choose to cover saliva testing or pay for the much more expensive serum testing. The practitioner also wrote she would be asking the state insurance commissioner’s office to investigate why an insurance company would unnecessarily drive up the medical costs against a practitioner’s choice if a less expensive, valid procedure is available. In this instance, coverage of saliva testing was granted within 24 hours.

What about insurance coverage for capillary blood spot testing?
There is no valid reason why dried blood spot testing should not be covered as a reimbursable procedure. Capillary blood has been validated in the literature and used for infants for over 30 years. The only issue I’ve seen is where the insurance company denied coverage based on the laboratory listed for doing the testing, one which is known for saliva testing.

Jim Paoletti, Pharmacist, FAAFM

IOM's Report: Vitamin D Daily Intake Recommendation - by Mark Newman, MS

2011-02-10T15:09:00.000-08:00

By guest blogger - Mark Newman, MS

The Institute of Medicine of the National Academies offered up new recommendations for daily intake of vitamin D and calcium late last year. The new Recommended Dietary Allowance (RDA) is 600 IU/day. They define the RDA as “levels of intake that are likely to meet the needs of about 97.5% of the population.” The Upper Level Intake is listed as 4,000 IU/day, which is an increase.

These conclusions are in sharp contrast to the vitamin D zealots of the world, the most aggressive of whom are calling for 5,000-10,000 IU/day to achieve the health benefits of vitamin D sufficiency. I happened to be at the CDC recently for a meeting with some folks very involved in vitamin D research. These are fairly conservative research types (not to be confused with the vitamin D zealots) and the group of renowned epidemiologists was disappointed with the ruling, to say the least. The difference of opinion between the vitamin D research world and the IOM is vast, so let’s break this down, so you can make some reasonable decisions for you, your family, and your patients ....

Read more of the original blog

Patient Assessment: Correlating Patient Symptoms with Test Results

2011-02-02T17:04:00.000-08:00

Jim Paoletti, Pharmacist, FAARFM, Director of Provider Education at ZRT Laboratory, interview with Robert Kress, RPh, on Profit Pharmacy Monthly show on "Patient Assessment: Correlating Patient Symptoms with Test Results." Click here to listen.

Hypothyroidism

2011-01-10T14:51:00.000-08:00

Jim Paoletti, Pharmacist, FAARFM, talks about the causes, diagnosis and treatment options for hypothyroidism.

2010-12-29T09:58:00.001-08:00

Jim Paoletti, Pharmacist, FAARFM, Director of Provider Education at ZRT Laboratory, interview with Dr. Sherrill Sellman on What Women Must Know, Progressive Radio Network, on “What Women Must Know about Hormone Testing”, 11/01/2010. Click here to listen.

Use of Progesterone - Scientific References

2010-12-08T14:02:00.000-08:00

After publishing my blog "She needs progesterone, uterus or not!" I received a few requests for scientific references on beneficial effects of natural progesterone. Below is a list I hope you will find useful. I also posted a more extensive list of progesterone references divided into topic categories on ZRT website.

PROGESTERONE (General)

1. Speroff L, Glass R, Kase N; Gynecological Endocrinolgy and Infertility. 7th ed. Philadelphia: Williams & Wilkins, Inc.
2. Fraser, Ian S. Estrogens and Progestogens in Clinical Practice. London, England: Churchill Livingstone, 1998.
3. Holtorf K. The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? Postgraduate Medicine, Volume 121, Issue 1, January 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
4. Stanczyk, FZ. Percutaneous administration of progesterone: blood levels and endometrial protection Menopause: The Journal of The North American Menopause Society Vol. 12, No. 2, pp. 232-237
5. Leonetti H, Wilson KJ, Anasti J. Topical progesterone has an antiproliferative effect on estrogen-stimulated endometium. Fertil Steril Jan 2003. 79(1):221-22
6. Warren M, Shantha S. Uses of Progesterone in Clinical Practice. Int J Fertil 1999; 44(2):96-103
7. Girouard LG, Holm RC. The Role of natural Pogesterone in Natural Hormone Replacement Therapy. IJPC May/June 2001
8. Stephenson K, et al. Trasndermal Progesterone: Effects on Menopausal Symptoms and Thrombotic, Anticoagulant, and Inflammatory Factors in Post Menopausal Women. IJPC Sept/Oct 2003
9. Moskowitz D; Changing Views: The Emergence and Efficacy of Natural Hormones in the Treatment of Menopause. JANA. Fall 2000;3(3):36-44.
10. de Lignières B, et al; Risks and Benefits of Hormone Replacement Therapy. Cephalalgia. 2000.20(3):164-169.
11. de Lignières B, et al; Pharmacodynamics of Oestrogens and Progestogens. Cephalalgia, 2000:20(3):200-207.
12. Ward D; Natural Progesterone: The “Feel-Good” Hormone. Vitamin Research Nutritional News April 1997.
13. de Lignières B; Oral Micronized Progesterone. Clinical Therapeutics. 1999; 21(1):41-60.
14. Martorano JY, et al; Differentiating Between natural Progesterone and Synthetic Progestins: Clinical Implications for Premenstrual Syndrome and Perimenopause Management. Comp Ther. 1998; 24(6/7): 336-339.
15. Barentsen R, et al; Progestogens: Pharmacological Characteristics and Clinically Relevant Differences. J Eur Menopause 1996; (4):266-271.
16. Maxson WS, et al; Bioavailability of Oral Micronized Progesterone. Fertility & Sterility. Nov. 1985; 44(5): 622-626.
17. Norman TR, et al; Comparative Bioavailability of Orally and Vaginally Administered Progesterone. Fertility & Sterility. Dec 1991; 56(6):1034-1039.
18. Richards-Kustan CJ, et al; Diagnosis and Management of Perimenopausal and Postmenopausal Bleeding. Obsteterics & Gynecology Clinics of N. America. March 1987;14(1):169-189.
19. Cicinelli E, et al; Effects of Progesterone Administered by Nasal Spray on the Human Postmenopausal Endometrium. Maturitas March 9, 1993;65-72.
20. Miles RA, et al.; Pharmacokinetics and Endometrial Tissue Levels of Progesterone After Administration by Intramuscular and Vaginal Routes: A Comparative Study. Fertil Steril, Sept. 1994; 62(3);485-90.
21. Leonetti HB, Wilson KJ, Anasi JN. ; Topical Progesterone Cream Has Antiproliferative Effect on Estrogen-Stimulated Endometrium. Fertil Steril, 2003 Jan;79(1):221-2.
22. Cheng W, et al; Two Antiatherogenic Effects of Progesterone on Human Macrophages; Inhibition of Cholestryl Ester Synthesis and Block of Its Enhancement by Glucocorticoids. J Clinical Endocrinology and Metabolism 1999; 84(1):265-271.
23. Desai H; Natural Progesterone Therapy in the Treatment of Preeclampsia. Unpublished, May 2001, Professional Compounding Centers of America.
24. Baulieu EE, Schumaker M. Neurosteroids, with special reference to the effect of progesterone on myelination in peripheral nerves. Mult Scler 1997;3:105-112.
25. Wright DW, et al. Serum Progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats. J Neurotrauma 2001;18:901-909.
26. Landau RL, et al.; Inhibition of the Sodium-Retaining Influence of Aldosterone by Progesterone. Recent Progress in Hormone Research. Nov 85 Vol 18:1237-1245.
27. Laidlaw, et al.; The Influence of Estrogen and Progesterone on Aldosterone Excretion. Recent Progress in Hormone research Feb 1962 Vol 22:16-171.
28. Landau RL, et al; The Catabolic and Nutriuretic Effects of Progesterone in Man. Recent Progress in Hormone Research 1964 pg 249-284.
29. Corvol P, et al; Effect of Progesterone and Progestins on Water and Salt Metabolism. Progesterone and Progestins, 1983 pg 179-186.
30. Tavaniotou A, et al; Comparison between different routes of progesterone administration as luteal phase support in infertility treatments. Human Reproduction Update 2000; 6(2):139-148.
31. O’Leary P. Carlstrom K, Damber J, et al. Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women. Clin Endocrinol (Oxf). 2000 Nov;53(5):615-20.
32. Graham C; Physiological action of progesterone in target tissues. Endoc Rev 1997;18:502-519.
33. Leonetti H, Wilson J, Anasti J. Transdermal Progesterone Cream for Vasomotor Symptoms and Postmenopausal Bone Loss. Obstet Gynecol 1999 Aug;94(2): 225-8.
34. Kim S, Korhonen M, Wilborn W, Foldesy R, Snipes W, Hodgen GD, Anderson FD. Antiproliferative effects of low-dose micronized progesterone. Fertil Steril. 1996 Feb;65(2):323-31.
35. Gillet JY, Andre G, Faguer B, Erny R, Buvat-Herbaut M, Domin MA, Kuhn JM, Hedon B, Drapier-Faure E, Barrat J, et al. Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study. Maturitas. 1994 Aug;19(2):103-15
36. Burry K, Patton P, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1504-11.
37. Carey B, Carey A, Patel S, et al. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG. 2000 Jun;107(6):722-6.
38. Lane G, Siddle NC, Ryder TA, Pryse-Davies J, King RJ, Whitehead MI. Dose dependent effects of oral progesterone on the oestrogenised postmenopausal endometrium. Br Med J (Clin Res Ed). 1983 Oct 29;287(6401):1241-5
39. Rudel HW, Kinel Fa. The toxicity of progesterone. In International encyclopedia of pharmacology and therapeutics. Tausck M, editor. Pergamon Press, New York, 1971, pg 405-9.

What Testing to Use?

2010-11-15T13:55:00.000-08:00

Jim Paoletti, Pharmacist, FAARFM, talks about his preferred methods of laboratory testing, and when to use saliva and blood spot testing.

Thyroid Q & A with Jim

2010-11-04T08:54:00.000-07:00

QUESTION: I am a 34 year old female, type one diabetic. I am very fit, have good diet and currently preparing for a bodybuilding competition. I had some labs that came back with a very high reverse T3 of 746. My doctor says he thinks it is due to the stress on my body of training so hard. I am starting Cytomel to reverse the issue. Any idea why my T3 is so high?

ANSWER: Taking Cytomel (T3) will not correct the reverse T3 being too high. High reverse T3 is caused by poor conversion of the T4 produced in your thyroid gland to the active T3. There are numerous things that affect the enzyme that converts T4 to T3. You should read “Overcoming Thyroid Disorders” by David Brownstein. Stress, or high cortisol, is one of the chief causes of poor conversion, so your exercise program could be a source of the problem. Adaptogens may help with the stress response, but I would also look at all the possible causes of poor conversion to see what may apply to you personally.

http://www.zrtlab.com/about-zrt/thought-leaders.html

Converting Patients to BHRT from Conventional Therapies

2010-10-15T09:31:00.000-07:00

Determining dosages and managing symptoms in patients who want to covert from conventional therapies to bioidentical therapy can be one of the most difficult challenges facing the BHRT practitioner. Conventional therapies and dosages provide too much hormone, even if the manufactured product being used contains bioidentical hormone rather than a synthetic agent. Conventional oral estrogen therapies, such as Premarin® and Estrace®, create a supraphysiologic overall estrogen status. While Premarin® 0.625mg and Estrace® 0.5 mg produce an estradiol level equivalent to that seen in normal premenopausal women, because of the high conversion of oral estradiol to estrone in the first pass effect, estrone levels in women taking these doses are usually 3 to 7 times higher than the normal level of a premenopausal woman. In the case of Premarin®, the product consists of more estrone (50%) than estradiol (5-19%), and therefore patients are consuming a product with a high amount of estrone as well as highly converting the estradiol in the product to estrone. Estrone levels in women taking Premarin are most often 5-10 times higher than normal premenopausal levels when normal premenopausal estradiol levels are achieved.

Bringing the estrogen levels in these patients back to normal premenopausal women is not as simple as reducing the dose dramatically, or switching to a physiologic dose of bioidentical estrogens that would produce normal levels in most women. In these patients, changes in the estrogen receptors and the brain take place, and have to be considered when converting them over to physiologic doses of bioidentical estrogens.

Taking a supraphysiologic dose for a long period creates a higher threshold for estrogen in the brain. This is similar to the mechanism of narcotic tolerance or addiction. Giving a patient who has no pain, and therefore no need for morphine, a sufficient dose of morphine for several months raises the threshold for the narcotic, and removing the narcotic will create withdrawal symptoms. The same can be seen with supraphysiologic doses of estrogen used in convention therapies. If you stop the estrogen abruptly or decrease the dose too quickly, the patient can experience severe withdrawal symptoms of estrogen deficiency. For this reason, I always try to taper the estrogen dose down over a period of 2-6 months depending on the individual’s difficulty with withdrawal symptoms. Once I have the patient on a lower dose (Premarin 0.3 mg or Estrace 0.25 mg every other day at the most), I will switch over to a bi-est consisting of 50% estradiol and 50% estriol.

Because women vary significantly in their individual withdrawal symptomology, taping the dose should be scheduled in a manner that allows for flexibility to an individual’s response. In my opinion, it is sometimes physically and psychologically difficult for a woman to skip her estrogen dose entirely for even a day. Typically, I will ask the patient to reduce to half of her usual dose, and take this half dose every third day for a period or 9 to 12 days, while maintaining her present dose on the other days. If she tolerates this decrease, then I ask her to take the half dose 2 out of 3 days for 9 to 12 days. (Note: some patients need to reduce the dose for much longer periods of time in order to tolerate withdrawal symptoms well enough to reduce it again).

When a woman is exposed to high levels of strong estrogens (estradiol and/or estrone) for a sufficient period of time, the estrogen receptors are usually lower in number and responsiveness, or sensitivity, of the receptor. Over time the decrease in sensitivity may become permanent, at least to some degree, so the patient may never respond to estrogens in the same manner as a typical patient given estrogen replacement. Therefore, often these patients require a higher dose of a preparation such as biest. Although in almost every other type of patient, I always start at the low end of suggested estrogen dosing guidelines, with the patients who have been on supraphysiologic amounts of estrogen for years I start at the midpoint of the suggested range. And I do not hesitate to increase the dose if the patient suffers significantly from estrogen withdrawal symptoms.

The same excessive hormone burden is seen with the use of manufactured transdermal creams, lotions, gels and patches. These products produce supraphysiologic levels of the hormones they contain. Men that are administering conventional doses of topical testosterone have 5 to 10 times the amount of testosterone in their tissues than when they are 18 years of age. After several months on a high dose, the effectiveness of the testosterone wears off as receptors are down regulated. Usually the dose of testosterone is increased, until eventually the testosterone becomes ineffective at symptom management at even super high doses. Men that have to withdraw from these supraphysiologic doses can suffer the symptoms of apathy, muscle weakness, decrease in stamina, depression and even suicidal thoughts.

Due to the wide variance in degree of testosterone withdrawal symptoms in men, I have not yet determined a tapering program. I have tried, or seen tried, up to a 50% weekly reduction in the amount of testosterone administered. With the use of a cream or gel, I usually ask the patient to not use the product for a few days to a week. If they feel poorly, they go back to using the product at 75% to 90% of the former dose for the same amount of time that they went without any supplementation; then repeat this schedule until physiologic levels are reached.

Changing a synthetic progestin to bioidentical progesterone, or just adding progesterone, is much easier. Immediately stop the progestin and start progesterone. Progesterone has effects on estrogen synthesis and metabolism, as well as increasing sensitivity of the estrogen receptors. These effects may not be fully appreciated for several weeks. Also, synthetic progestins can take several weeks to clear completely form the body. So it is best to make the switch as soon as possible. Withdrawal will not be an issue because of the slow clearance of the progestins, and because the progestins outside of the uterus do not produce the same effect on the receptors as progesterone. In essence, you are replacing a progesterone antagonist with progesterone.

When converting patients from conventional to bioidentical therapies, practitioners need to keep the patient’s comfort in mind. It can be a difficult time for patients of either sex, and the practitioner should show flexibility and patience in obtaining the long term goal of establishing physiologic levels.

Jim Paoletti, Pharmacist, FAARFM

The Physiologic Role and Use of Estriol

2010-10-05T10:40:00.000-07:00

Jim Paoletti, Pharmacist, FAARM, talks about the efficacy of estriol in hormone restoration therapy.

Thyroid Q and A with Jim

2010-09-22T14:13:00.000-07:00

QUESTION:
I have been on thyroid medicine for about 4-5 years now. Every time I see my doctor, he increases my dose and I am now on Synthroid.88mg daily. Sometimes I skip my dose and I have more energy without the medicine; I am thinking more clearly and don't feel run down, as I do when I take my pill. What are the consequences to stopping the medicine? How is not taking the pill for 3 days or more affect my body?

JIM'S ANSWER:
If a patient is not converting the Synthroid (which is T4) to the active T3 hormone in their body, then they produce reverse T3 from the T4. Reverse T3 actually blocks the effects of the active hormone T3 at the T3 receptor. So in essence the T4 the patient is taking is not helping and may be worsening the situation. Rather than produce the active hormone T3 in the proper amount from their medication, patients actually produce too much of an antagonist of T3.

However, I would not recommend stopping your medication cold turkey. And although there are a number of nutritional factors that affect thyroid function, there is no alternative to thyroid hormone if you truly need it. I suggest you find a functional medicine doctor that understands thyroid production, binding, conversion and nutritional needs and have them reassess your thyroid function before you make any drastic changes in therapy.

She needs progesterone, uterus or not! The practice of evidence based medicine and the use of progesterone.

2010-09-16T11:21:00.000-07:00

Much too often I get asked about the statement “she doesn’t need progesterone if she doesn’t have a uterus”. It is hard to conceive that medical schools are still teaching the idea that a woman without a uterus does not need progesterone. It’s also hard to believe that large number of practitioners consider this statement true without questioning it. It is not supported by physiology, biochemistry or science.

Synthetic progestins do not imitate well the actions of progesterone outside of the uterus. In fact, medroxyprogesterone acetate (MPA), the most frequently prescribed synthetic progestin in the U.S., produces the exact opposite effects of endogenous progesterone in almost all, if not all, organs or systems outside of the uterus. The drug first given to us to mimic the effects of natural progesterone works only like progesterone in one organ and everywhere else produces the exact opposite effect of progesterone!

This misguided philosophy results in practitioners not giving progesterone or progestins to patients who have had a hysterectomy, and therefore practitioners never see a direct comparison of the effects of the two different agents on the rest of the body. The above statement helps to keep practitioners from comparing the known proven effects of progesterone on many body systems to the results caused by administration of the “progesterone-mimicking” synthetic progestins. If practitioners would look at the lack of science behind the statement, and the body of evidence supporting overall health benefits of progesterone itself, synthetic progestin use would most likely plummet.

Limiting the use of progesterone to women who have a uterus ignores the science that progesterone has beneficial effects outside of the uterus. Progesterone receptors have been identified in almost every cell in the body; therefore, progesterone has functions throughout the entire body. A quick look at the evidence shows many favorable effects of progesterone, whereas MPA produces unwanted side effects or risks which are the exact opposite of the actions of progesterone.

Breast cancer risk is a chief concern for the majority of women considering hormone replacement therapy. Evidence overwhelmingly shows that any synthetic progestin use, even for a limited time, increases the risk of breast cancer. The longer the use of progestin, or the more testosterone-like the synthetic progestins, the greater the risk becomes. The studies may disagree on how high the risk increase is, but they all agree that synthetic progestins significantly increase the risk of breast cancer. The mechanisms have been identified for the most part, and they are opposite to the mechanisms of endogenous progesterone in breast tissue.

In opposition to the increased risk of synthetic progestins, bioidentical progesterone has been shown to possess anti-proliferative and anti-cancer properties. A low level of endogenous progesterone is associated with an increased risk of breast cancer. Clinical studies suggest progesterone therapy protects against breast cancer. Some studies have even shown a decreased risk of breast cancer when natural progestin is added to estrogen therapy.

Speroff’s textbook, Clinical Gynecologic Endocrinology and Infertility, states that the proliferative action of estrogens and the progesterone actions of differentiation and apoptosis are the same in the breast tissue as in the uterus. Therefore, progesterone, and only progesterone, can protect the breast tissue from cancer by the same mechanism that any progestin protects the uterus. Looking at the science, the above statement needs to be modified to “she doesn’t need progesterone if she doesn’t have a uterus or breasts”.

The number one killer of women over the age of 50 is cardiovascular related events. MPA has been shown to completely negate the favorable effects of estrogen on the maintenance of a healthy lipid profile and the cardiovascular benefits of estrogen, and significantly increase cardiovascular risks. In contrast, progesterone works synergistically with estrogen to increase lipid maintenance and cardiovascular health. Based on the difference between MPA and progesterone, the writers of the largest hormone study at its time, the 1995 PEPI study, concluded that “we should be giving woman natural progesterone” (this conclusion has still to be incorporated into mainstream medicine). Based on the evidence, the statement needs to be modified to “she doesn’t need progesterone if she doesn’t have a uterus, breasts or a cardiovascular system”.

Other major health concerns for the aging female patient are the development of osteoporosis and dementia. Progesterone works synergistically with estrogen to provide better bone remodeling through stimulation of bone growth, while progestins do not. While progesterone provides neuroprotective benefits for the nervous system, side effects of synthetic progestins are the opposite. Now we need to correctly state, “she doesn’t need progesterone if she doesn’t have a uterus, breasts, a cardiovascular system, bones, or a brain”!

Additional evidence continues to demonstrate the opposite effects of progesterone vs. the synthetic substitutes. MPA is proliferative and inflammatory; progesterone has been demonstrated to be neutral or slightly anti-inflammatory and anti-proliferative in its actions. Progesterone is the drug of choice for protection from further damage in traumatic brain injuries, and in at least two small studies progesterone has been shown to help reverse the debilitating effects of brain injury. MPA causes degenerative changes in the liver, while progesterone does not. Physiologic levels of progesterone augment the release of insulin from the pancreas, while synthetics increase insulin resistance.

The evidence clearly indicates that bioidentical progesterone provides a number of protective benefits not offered by synthetic progestins. Synthetic progestins instead increase risks associated with loss of these protective benefits. Therefore, I would recommend that our health professional educators examine the evidence and teach what the scientific evidence demonstrates: a woman does not need a progestin if she does not have a uterus, but she requires progesterone when it becomes deficient in perimenopause to continue to provide protection of her breasts, heart, blood vessels, bones, nervous system muscles, liver, skin, and perhaps much more yet to be discovered.

Jim Paoletti, Pharmacist, FAARFM

Q & A on Thyroid - watch the interview

2010-09-01T14:07:00.000-07:00

Jim Paoletti, Pharmacist, Director of Provider Education at ZRT Laboratory, answers some common patient questions on thyroid conditions.

Q: My thyroid blood tests came back normal, but my thyroid is still enlarged. Should I be worried?

Q: I have had hypothyroidism for several years and cannot maintain my weight. What are your suggestions for what I should eat and what I should steer clear of in regards to my underactive thyroid?

Q: I am feeling tired all the time and I lost weight although I eat constantly, and always feel hungry. I have been tested for thyroid problem and Iodine levels, and all of my blood work came out in the normal range. Could this be hypothyroidism, or just stress and high metabolism?

Thyroid Q & A with Jim

2010-08-23T11:20:00.000-07:00

QUESTION: I have had hypothyroidism for several years and cannot maintain my weight. What are your suggestions for what I should eat and what I should steer clear of in regards to my underactive thyroid?

JIM'S ANSWER: There are a few things in the diet that can affect the conversion of T4 to the active T3. Excessive cruciferous vegetables is one (Brussels sprouts, cauliflower, broccoli, etc). What is more important is supplementing a good daily vitamin and mineral. Find a doctor who knows how to take a functional approach to thyroid and will determine if you are producing enough hormone, metabolizing it correctly, and knows the nutritional requirements for optimal function of the thyroid receptor.

Which Testing to Use???

2010-08-04T10:15:00.000-07:00

A question I get asked frequently is which method I prefer for measuring hormones, ZRT saliva testing or ZRT capillary blood spot testing. Since both methods have shown to provide good results that reflect symptomology and represent the tissue levels of the hormones, my answer is whichever is appropriate for the individual patient.

Saliva testing is the only way I test cortisol levels. I strongly believe in getting a 4-point cortisol (4 times a day) pattern to know best how to treat the individual patient. Presently, venous serum and capillary blood spot testing have reference ranges for a twice a day measurement only, and the normal range for venous serum in the late afternoon is much too wide to be very useful.

ZRT’s saliva testing has the advantage of the data that has been collected for over 1 ½ million patients, which correlates levels to symptoms and dosing. The more data, the easier it becomes to fine-tune the target range. Hormones in saliva are fairly stable. For patients having difficulty getting enough saliva for the morning sample, the saliva can be kept in the freezer and added to over 2-3 days to reach a sufficient amount. Saliva can be kept in the freezer for up to 30 days without any significant loss of hormones.

Saliva testing does have some disadvantages, and there are cases where capillary blood spot testing would be preferred. Some patients do not believe they can collect any significant amount of saliva, whereas blood spot collection can offer a simple solution. Other patients may have difficulty in generating saliva, such as with autoimmune disorders like Sjogren’s syndrome, or patients on anti-cholinergic or antihistamine medications.

In my opinion, saliva testing should be avoided in patients taking their hormones by sublingual or buccal administration. These routes cause an accumulation of hormone in the tissue locally, and the value obtained by saliva testing will over-represent the amount present in the tissue systemically. I always use capillary blood spot testing when hormones are administered under the tongue or in the cheek pouch.

There are substances which are too large to be measured in saliva. These include the endocrine hormones, thyroid and insulin, as well as glucose, cholesterol, and Vitamin D. The levels of all of these are important to know when evaluating the hormone balance of a patient. Insulin, cortisol, and thyroid imbalances are the chief disrupters of sex hormone balance. Many of the symptoms thought to be caused by deficiencies or imbalances in the sex steroids can be caused or exacerbated by imbalances in these other endocrine hormones. Recent research has shown Vitamin D important to heart health, cancer protection, and the function of the thyroid receptor.

Because of these factors, I commonly use ZRT’s combination test kit, measuring both saliva and blood spot which allows me to get the best overall evaluation of the endocrine system.

For example, most patients over the age of 40, male and female, have some degree of adrenal dysfunction. Even if it’s not to the degree where it is significantly affecting symptoms, it is helpful to catch adrenal dysfunction at an early stage to prevent this condition from getting worse. Only a 4-point saliva cortisol test can accurately measure fluctuating cortisol. Many patients have symptoms that can be related to less than optimal thyroid function, and thyroid function is significantly affected by cortisol and progesterone level. That is why I find myself commonly wanting to examine thyroid levels in patient’s initial evaluation. In addition, I always test Vitamin D, one of many keys to proper thyroid function. Thyroid and Vitamin D can only be tested with capillary blood spot testing.

The sex steroids can be accurately tested by either method – saliva or blood spot. I personally tend to gravitate towards saliva testing for females, most likely because I have used it for ten years and am extremely comfortable with the target ranges I strive for. However, it is hard not to recommend blood spot testing. It’s so easy and convenient for the majority of patients to do at home, or can be easily done in a practitioner’s office. For male patients, I tend to prefer blood spot testing, so I can also test the PSA. Blood spot also offers the advantage of looking at the cardio metabolic risk factors, which is appropriate for so many individuals. I find many patients have put off measuring these risk factors because of the inconvenience of seeing the doctor and then a phlebotomist for conventional venous serum testing.

View tests offered in saliva.

View tests offered in blood spot.

Thyroid Q&A with Jim

2010-07-16T10:29:00.000-07:00

QUESTION: Eight weeks ago, my lab results showed my thyroid level at around 20, and I was put on Synthroid 125 mg. I just had my level checked again and my thyroid level went down to 0.05. My doctor had to decrease my dosage to 90 mg of Synthroid. Is it hypothyroidism or hyperthyroidism?

JIM'S ANSWER: The "thyroid level" you mention that went to 0.05 is most likely TSH. This is not a measurement of an actual thyroid hormone; it is a measurement of the substance released that tells your thyroid gland to make more thyroid hormone. Doctors routinely use TSH to necessitate the need for thyroid therapy and adjust dosage, but TSH should not be the only consideration for such, and overall is a poor way to evaluate thyroid hormone function. Synthroid 125 mcg is T4, and is more T4 than most people product daily in their prime. No one should ever be started that high. Eight weeks in not long enough to let the thyroid binding globulin level out; testing should be done no sooner than 12 weeks following any dosage change. Lastly, the number one cause of all thyroid disorders is autoimmunity, so your doctor should ALWAYS get at least a TPO (thyroid peroxidase antibody) test done.

Timing of Thyroid Replacement Therapy and Interpretation of Thyroid Levels

2010-02-22T14:16:00.000-08:00

Watch Jim Paoletti, Pharmacist, FAARFM, talk about a critical aspect in interpretation of thyroid levels for a patient on Thyroid Replacement Therapy (TRT), which is the timing of the sample vs. the timing of the last dose of TRT.

For the original video, click here.

Does she/he really need Thyroid Replacement Therapy?

2010-02-09T12:29:00.000-08:00

Watch Jim Paoletti, Pharmacist, FAARFM, Director of Provider Education at ZRT Laboratory, talk about underlying causes of hypothyroidism and correct thyroid replacement therapy administration.

For the original video, click here.

Salivary Cortisol Testing -- Single Versus Multiple Daily Tests

2010-01-11T09:25:00.000-08:00

Salivary cortisol testing is the preferred clinical method for measuring human cortisol levels. It has several obvious advantages over blood tests, such as greater validity for tissue levels of cortisol, the convenience of home testing, non-invasiveness, and zero risk of infection. But arguably one of the most important features it offers is the ability to take multiple test samples during the same day. Although urine can also be sampled more than once a day, the constant supply of saliva versus the intermittent supply of urine allows salivary cortisol levels to be taken on demand at any time of the day or night.

The rhythmic circadian fluctuations of cortisol secretion make it virtually impossible to accurately determine cortisol levels by taking a single sample. Cortisol levels can change dramatically within an hour, and it is how they change over a 24 hour period that often yields the most clinical insight. For example, a common pattern seen in people under stress is above normal cortisol in the morning (8:00 AM), which drops to low or below normal by noon and remains low throughout the rest of the day. A single 8:00 AM sample is in no way an accurate indicator of cortisol levels for other parts of the day or of the pattern of change. Cortisol concentration levels vary 6-8 times in magnitude during a normal 24 hour period. Taking a single sample at the beginning of the day, which is the most common time for single samples to be taken, can be so misleading that it often results in inappropriate interpretation of the overall cortisol status and consequent therapy for the patient.

The following example illustrates the clinical implications of testing cortisol only once compared to testing multiple times on a single day.

Mary goes to her physician with a number of symptoms including early morning and mid-afternoon fatigue and mild depression. He decides to test her cortisol levels and has an early morning sample taken, unaware that she is not sleeping well and that cortisol can be elevated in the morning due to the stress of restless sleep the night before. When he receives Mary’s test results showing an elevated morning cortisol, he provides treatment to flatten her cortisol levels because he views her elevated cortisol as a health risk. Mary follows the treatment as directed, but feels worse. She returns a few weeks later complaining that her symptoms are increasing in duration and intensity, and that she has developed new ones as well. Thinking he is not doing enough to flatten her cortisol, the physician doubles her dosage.

Mary gets even worse and consults another physician in her area. Her new physician also says he expects her adrenals are involved in her health problems. After a quick glance at her single sample test result, he tells her he wants to run the salivary cortisol test again, but this time he wants to test her cortisol levels 4 times in the same day.

The results show that even though her morning cortisol level was elevated, as it was in her previous test, the other three cortisol levels were actually low. Indeed, viewing the multiple samples taken on the same day, Mary sees that she is not suffering from an excess of cortisol, but in actuality has low cortisol during most of the day.

As you can see, the clinical implications of using a multiple sample rather than a single sample cortisol test are significant. The physician who used the 8:00 am cortisol level as the sole laboratory indicator of Mary’s condition misdiagnosed her and prescribed the wrong treatment. If he had been aware of the circadian variation of cortisol and the consequent importance of looking at the pattern of change, he would have used a more accurate test strategy and achieved a much better outcome for his patient.

Health care practitioners who understand that cortisol normally fluctuates throughout the day routinely order multiple cortisol samples to be taken over a single day. The most common pattern is four times per day at 8:00 am noon, 4:00 pm, and before bed.

In summary, cortisol has large daily fluctuations from its peak to its nadir. Because of this normal variation, the use of multiple salivary cortisol tests over a single day is the most accurate way to gain insights into the daily fluctuating cortisol pattern of patients and arrive at a proper diagnosis and treatment protocol. The astute health care practitioner uses laboratory tests that most accurately reflect the underlying physiology of the body system(s), they are investigating. Cortisol testing is no exception.

Jim Paoletti, Pharmacist, FAARM

Does She Really Need That Estrogen? Video - Part 2

2009-12-11T12:18:00.000-08:00

Jim Paoletti, Pharmacist, FAAFRM talks about common misconceptions regarding lack of estrogen in perimenopausal and menopausal women, and how frequently their symptoms are incorreclty diagnosed, which results in prescribing excessive dosages of estrogen.

Watch Part 1 of the video in Jim's earlier blog of October 29, 2009.

For the original video, click here.

Does She Really Need That Estrogen? Video - Part 1

2009-12-11T12:06:00.000-08:00

Jim Paoletti, Pharmacist, FAAFRM talks about common misconceptions regarding lack of estrogen in perimenopausal and menopausal women, and how frequently their symptoms are incorreclty diagnosed, which results in prescribing excessive dosages of estrogen.

Watch Part 2 of the video in Jim's earlier blog of October 29, 2009.

For the original video, click here.

Safe Estrogen Metabolism

2009-11-12T08:17:00.000-08:00

In my opinion we often overlook the best ways, both physiologically and economically, of ensuring safe metabolism of estrogens to decrease the risk of cancer. The majority of a woman’s estrogens are normally conjugated in the liver and eliminated in the stool. To ensure that this natural method of safely metabolizing estrogens is optimized, the first thing I strongly suggest before initiation of any estrogen therapy is liver detoxification. Make sure the bowels are moving regularly before detoxifying. In addition, if the normal flora in the lower intestine has been disrupted, the result can be an increase in the enzyme activity of beta-glucuronidase. This enzyme cleaves the conjugated estrogen and re-circulates the estrogen that was conjugated and meant to be eliminated from the body. Therefore, I also strongly recommend at least a month or two of good probiotic therapy supporting Bifobacterium bifidium to restore the normal flora of the lower intestine.

Any form of estrogen other than estriol increases the amount of estrogen that is metabolized down the pathway to form catechol quinones, the metabolites that form DNA adjuncts that cause DNA mutations which can lead to cancer. Any estrogen therapy other than E3 in any amount increases dangerous metabolites. Therefore, I recommend to never give women more estrogen than absolutely needed. This can only be accomplished by addressing progesterone deficiencies, as well as insulin resistance, adrenal, and thyroid issues to eliminate their participation as a possible cause of supposed “estrogen deficiency” symptoms, as well as by measuring estrogen levels, the only true way to determine if estrogen itself is actually needed. Symptoms alone can never guarantee the need for estrogen.

Metabolism to the unsafe 4-OH metabolites can be inhibited by reducing lipid peroxidase activity. This is best accomplished by avoiding trans-fats and taking an antioxidant combination. Avoidance of pesticides also decreases the amount of unsafe metabolites produced.

Of the estrogen that is not conjugated, the vast majority should be normally methylated, producing safe estrogen metabolites. Methylation is dependent on the COMT enzyme, which is dependent on Vitamins B1, B6, B12 and folic acid. I strongly recommend these vitamins and a methyl donor such as MSM or TMG. At this point over 99% of any estrogens produced by the body or given (as long as not excessive) should be going down the normal pathways to safe metabolites. That leaves very little going down the remaining pathways, forming cancer causing depurinating adducts.

Additional safe metabolites can be encouraged by glutathione activity, which can be increased by NAC, Cysteine, aged garlic or MSM (to provide sulfur) or by administration of glutathione itself. Sulforaphane, an organosulfur compound found in cruciferous vegetables, can convert the estrogen glutathione conjugate metabolite formed just prior to the formation of the dangerous depurinating adducts back to the 4-OH metabolite, where it can then be acted on by COMT or glutathione. In other words, it takes the metabolite about to form the dangerous structure back to one where you have at least 3 more shots at metabolizing it safely.

With so many natural ways to ensure normal safe metabolism, concentrating on the ratio of the 2-OH and 16-OH ratios seems an inefficient way to address safe estrogen metabolism. Although many believe the 16-OH metabolite to be carcinogenic, I am not convinced of it. In vivo work by Cavalieri and associates has concluded that the 16-OH metabolites cause no further damage. This work also shows that the dangerous catechol quinones are formed from both estradiol and estrone, so both have the potential for forming the metabolites which initiate cancer. Although I do suggest the use of I3C or DIM in patients of either sex to increase the overall metabolism of estrogens and help reduce the burden of excess estrogens, I do not feel that increasing the proportion of 2-OH metabolites compared to 16-OH metabolites necessarily reduces the risk of breast cancer.

In my opinion, those that push for testing of these substances are not using patient’s money most efficiently and are concentrating on a controversial downstream effect, instead of optimizing the system that is already in place to protect against dangerous estrogen metabolites.

To summarize, here is how I approach safe estrogen metabolism:
• Ensure proper liver and bowel function to conjugate and eliminate the conjugated estrogens
o Liver Detox
o Fiber to help optimize bowel movements, increase SHBG, and eliminate bile toxins
o Probiotic therapy
• Balance estrogen with progesterone which has been shown to reduce the estradiol-induced proliferation of breast tissue and cause natural cell death
• Avoid pesticides and trans-fats
• Never give any more estrogen than absolutely necessary. Address need for progesterone first, as well as any adrenal, insulin resistance, or thyroid issues. Always dose estrogen low initially and increase dose slowly
• Ensure proper methylation with active B1, B6, B12, folic acid and a methyl donor
• Support immune function, including restoring DHEAs levels to normal
• Take an antioxidant combination of at least Vitamin C and Vitamin E

Optional additional considerations:
• Glutathione support
• Sulforaphane
• I3C or DIM to increase estrogen metabolism
• Calcium-D-Glucorate to inhibit beta-glucuronidase

Two excellent references I would recommend are:
“What Your Doctor May Not Tell You About Breast Cancer” by John Lee, MD and David Zava, PHD
And
E.L. Cavalieri, E.G. Rogan and D. Chakravarti. Initiation of cancer and other diseases by catechol ortho-quinones: A unifying mechanism. CMLS 59 (2002), 665-681.

Jim Paoletti, Pharmacist, FAARFM Nov. 2009

Does She Really Need That Much Estrogen? – Part 2

2009-10-29T12:16:00.000-07:00

Historically women have been given too much estrogen even when they do need estrogen replacement. Excessive estrogen may help control the hot flashes for a month or two, but eventually the symptoms return. A surplus of estrogen causes the same symptoms as insufficient estrogen, just with a slight time delay before the symptoms return. Too much estrogen at first increases the number of estrogen receptors, but after a period of time the body decreases the number of receptors, so the estrogen cannot work properly no matter how much is there.

Premarin® 0.625 mg or Estrace® 0.5 mg, dosages commonly administered for years, are excessive estrogen burden for any woman. The majority of estradiol given by mouth is converted to estrone, another strong estrogen. Estradiol levels resulting from these doses may be at normal premenopausal levels, but estrone levels will be significantly higher than normal. High estrone levels lead to symptoms of estrogen dominance and significantly increase the risk of breast cancer. Premarin® contains 50% estrone, and 5-19% estradiol (along with a bunch of horse estrogens!). The estradiol in it for the most part is quickly converted to estrone, so what the patient is really receiving is a strong dose of estrone. While Premarin® produces normal premenopausal levels of estradiol, estrone levels are usually 7-10 times higher than they should be. Clinicians usually only measure the estradiol level to manage therapy.

Estrace® is bioidentical estradiol, but again the usual doses given by mouth produce too high an estrone level , usually 3-5 times higher than normal.
Topical administration of estrogen is safer and enables administration in a manner where the correct ratio of estradiol to estrone can be accomplished. Topical administration is a very efficient manner to deliver hormones, so compared to the oral route much lower doses are required. But because many practitioners have erroneously assumed that venous blood measurement can be used to determine the amount of topical dosing, doses much higher than physiologic amounts are too commonly used. Capillary blood or saliva testing must be used with topically applied hormone to get a true representation of the amount of hormone that is being delivered to the tissues where the hormones work. Too often excess hormone is used based on serum testing, then the symptoms return as a result, and then even more hormone is given. Symptoms of too much of any hormone are very, very similar to symptoms of too little of that hormone! If the hormone has worked for a period of time, and is no longer effective, it is usually a good indication that too much hormone has been administered.

The keys to physiologic estrogen replacement therapy are:
• Make sure the patient needs estrogen by correlating symptoms with measurement of levels
• Never assume a woman needs estrogen
• Always restore progesterone to a physiologic level before assessing how much, if any, estrogen is needed
• Test cortisol with a 4 times a day saliva test to help determine adrenal influence on “estrogen deficiency” symptoms. Address as necessary.
• If symptoms of hypometabolism (hypothyroid) are present, test the TT4, fT4 direct, fT3 direct, TPO and TSH to properly assess. Address appropriately.
• Check insulin resistance if symptoms indicate and address appropriately
• ALWAYS start very low on estrogen dosing and make changes slowly.
• Take steps to ensure safe estrogen metabolism by optimizing liver conjugation, bowel elimination, methylation and glutathione conjugation, and by reducing lipid peroxidase activity.

Jim Paoletti, Pharmacist, FAARFM

Does She Really Need That Estrogen? - Part 1

2009-10-29T12:14:00.000-07:00

Historically, it has most often been assumed that when a woman enters perimenopause and begins to experience symptoms which include hot flashes, it means she needs estrogen. However, a woman’s estrogen levels do not decline until the last 6 to 12 months of perimenopause. When she first enters perimenopause, estradiol levels usually rise slightly. The hot flashes that she experiences at this stage of life are not caused by a lack of estrogen.

Many health practitioners were taught to measure FSH levels to confirm that estrogen levels were low. However, estrogen has been shown not to be the major controller of FSH. FSH is controlled primarily by inhibin, a hormone produced in the corpus luteum. When a woman does not ovulate, she does not produce a corpus luteum or inhibin, and the FSH rises due to a lack of inhibin, not a lack of estrogen. Progesterone is also produced by the corpus luteum, so elevated FSH is reflective of a decrease production of progesterone. A physiologic amount of progesterone is required to make estrogen work correctly. In early peri-menopause, a woman’s hot flashes are most often caused by a lack of progesterone, not a lack of estrogen.

Although progesterone is a key in obtaining optimal effects of estrogen, other hormones may cause or influence the symptoms we often perceive as a lack of estrogen. High cortisol levels can also cause weight gain, irritability, irregular cycles, and hot flashes even in the present of normal estrogen levels. Consistent low cortisol can also cause or aggravate hot flashes. Low thyroid function can cause similar symptoms that appear as estrogen deficiency; insulin resistance can do the same. Over the recent years, one of the largest changes in the approach to obtaining physiologic hormone balance in women is the way estrogen replacement is approached. Since so many other hormone levels affect estrogen and estrogen receptors, correcting other hormone issues have led to further and drastic reduction in the amount of estrogen commonly administered. In other words, if the other hormone or endocrine issues are addressed first, then the amount of estrogen required to treat the assumed “estrogen deficiency” symptoms becomes smaller.

No symptom or set of symptoms guarantees a woman needs estrogen, as some symptoms can be explained by another possible hormone deficiency. Vaginal dryness or atrophy, which almost always indicates a lack of estrogen, can exist when estrogen levels are normal. Vaginal tissues are also supported by testosterone and thyroid, and a significant deficiency in one or both of these hormones can be the source of the problem. Lack of progesterone could result in the estrogen not being effective. Properly assessing estrogen need and assessing response to estrogen therapy requires balancing the other endocrine hormones simultaneously or prior to estrogen administration.

Although most of the time, measurement of estrogen levels via testing is very accurate, there is a small window of time in woman’s life when it may not reliably indicate estrogen need. Estradiol levels begin to fluctuate during peri-menopause, with much wider vacillations towards the end of perimenopause. During this period, proper measurement of all other hormone levels along with symptom assessment should be reviewed. The best approach would be to correct deficiencies or issues with progesterone, cortisol, thyroid, insulin resistance, and nutrition or lifestyle, then correlate remaining symptoms with levels, and address estrogen therapy as required.

Jim Paoletti, Pharmacist, FAARFM

BHRT - Health and Wellness Solutions

2009-10-13T11:39:00.000-07:00

Jim Paoletti, Pharmacist, ZRT Director of Provider Education, is interviewed by Dr. John Wycoff on Health and Wellness Solutions show, on BHRT, 7/25/2009. Listen the the interview here under Radio Interviews tab.

Understanding BHRT

2009-10-13T11:33:00.000-07:00

Jim Paoletti, Pharmacist, FAARFM, ZRT Director of Provider Education, is interviewed by Daniel Davis on Beyond 50 radio on Understanding Bioidentical Hormone Replacement Therapy (BHRT), 9/04/2009. Click here to listen.

Stop the Testosterone Madness!

2009-08-27T08:29:00.000-07:00

Men using topical testosterone replacement products are typically and commonly given too much hormone. The explanation for this erroneous tendency seems to be rooted in the standards for dosing that have been established on false assumptions, misconceptions, invalid conclusions, and marketing instead of physiology and science. So why are the process for prescribing testosterone and standards of testosterone replacement so frequently misguided?

The problem of testosterone overdosing starts obviously with incorrect dosing principles for testosterone replacement products. For topical application, a physiologic daily dose of any of the sex steroids in either sex is approximately the same as our daily production during our prime, if you no longer make any of a hormone. With topical testosterone in males, typical doses are 5 to 10 times the amount of hormone a man makes when he is 18 years old. The physiological production of testosterone in a young adult male is approximately 6 mg per day. BHRT should be restoration therapy in the sense we should be dosing enough hormone to restore the level by adding to what the patient is still producing. A physiologic dose of topical testosterone for a male is 1 to 10 mg daily. Administration of too much hormone will suppress endogenous production and eventually lead to receptor down regulation.

A dose of 50 or 100 mg of topical hormone is a commonly administered dosage, which unfortunately is TOO EXCESSIVE an amount for men. So why is such a high dose prescribed?

The culprit is testing methods for topically applied hormone. No studies have ever validated the use of serum testing for topically applied hormone. No correlation has been shown between venous serum levels and bioavailability (available at site of physiologic activity) or long term efficacy. In contrast, Dr. Frank Stanczyk has shown that venous serum testing cannot be used to judge the effect in the uterine tissue for topically applied progesterone. Applying the principles of evidence based medicine and using the strongest scientific evidence instead of a manufacturer’s marketing piece, one would have to avoid using venous serum testing for any topically applied hormone.

Relying on the irrelevant serum testing method, drug manufactures lead us down the wrong road. They used venous serum levels to determine how much hormone in their topical products is “delivered” or “absorbed” or “bioavailable”. These terms have been bastardized by the pharmaceutical industry, which defines all these only by the amount of hormone seen in the serum. In medical use, bioavailability is defined as “the degree and rate at which a substance (as a drug) is absorbed into a living system or is made available at the site of physiological activity.” “Absorb” means “to take up especially by capillary, osmotic, solvent, or chemical action.” Both definitions have to do with the amount of hormone that goes into the system, not the amount left over in venous serum. “Delivered” is a label initiated by the drug manufactures so as to avoid the term dose in terms of topical manufactured products.

As a result of relying on serum testing for topically applied hormones, doctors and patients are confused as serum levels often go down initially, even if an amount as low as 5 or 10 mg daily is used. Since most males are still producing at least a fair amount of the original 6 mg daily, even 5 to 10 mg can bring their total level to higher than physiologically normal, resulting in a decreased endogenous production and down regulation of testosterone receptors, and the resulting loss of symptom management. The venous serum testing only reflects the endogenous hormone level and not the topically applied hormone, so the suppression of production causes a reduction in the serum level. Often the prescribing practitioner may increase the dose even higher because of the decrease in a venous serum level. This is blatantly incorrect! We give a patient testosterone, and because a level goes down, we give him more? Before increasing the dose further, should one not first be able to explain why the level would go down?

Resistance is the most common reaction I see to suggestions of reducing the dose of topical hormone. The lowering of estrogen dosages in women over the past 20 years to 1/10th to 1/20th or what was initially used met this type of resistance. One reason for the resistance is the lack of knowledge of any other approach to addressing the symptomology sufficiently. Another source of resistance is the amount of knowledge, education and time it requires to properly balance all hormones, nutrition and lifestyle factors, in opposition to simply increasing the dose of testosterone.

Other prescribers simply state that they do not understand saliva testing and/or that topical testosterone doesn’t work in men. These same practitioners fail to explain why venous serum doesn’t show a linear relationship to topical testosterone dosing, or why testosterone is the only hormone in either sex that doesn’t work topically.

This resistance results from the fact that it is much easier to follow suit and not have to learn and think how to correct the real problem. A vital solution to the issue of overprescribing and overdosing testosterone would be accurate and indicative hormone level testing and monitoring. Saliva testing and capillary dried blood spot testing present such an answer. The discrepancy between free and protein bound hormones becomes especially important when monitoring topical or transdermal hormone therapy. Studies show that this method of delivery results in increased tissue hormone levels, thus measureable in saliva, but no parallel increase in serum levels. With the use of dried blood spot testing, like saliva, hormones are present in the “capillary” blood from the finger and are representative of the hormones being delivered to other tissues of the body. With hormones delivered through the skin as supplements, the capillary dried blood spot hormone level rises in concert with an increase in salivary hormone levels because this represents hormone delivery to tissues throughout the body.

In sharp contrast, blood taken by conventional venipuncture rises very little, not at all, or even decreases in some cases with skin delivery of hormones. This might seem odd, but blood being delivered back to the heart through the veins has already delivered its bioavailable hormone load, and hormones remaining in the bloodstream are tightly bound to serum proteins such as SHBG and albumin.

Jim Paoletti, Pharmacist, FAARFM

Does she/he really need Thyroid Replacement Therapy?

2009-08-07T15:56:00.000-07:00

In many cases where symptoms of hypothyroidism exist, the cause of the problem may not be the lack of ability to produce an optional amount of thyroid hormone from the thyroid gland. Before initiation of Thyroid Replacement Therapy (TRT), the capacity of the gland to produce the thyroid hormones, primarily T4, should be first determined. Total T4 (TT4) levels should be evaluated to see if they are optimal. If lack of production is determined, then possibly the patient does not have sufficient quantities of the necessary elements required for making thyroid hormone, tyrosine and iodine. Obtaining tyrosine is usually not a problem, as most people get it in their diet. Vegans and vegetarians may lack tyrosine. This might also be the case with body builders who take amino acids supplements, and tyrosine is blocked by competitive absorption with the other amino acids. Iodine deficiency exists in a lot of patients.

If thyroid production is optimal, then one should consider whether there is optimal unbound of free hormone available to work at the receptor. Excessive binding can be commonly caused by oral estrogen therapy, including oral contraceptives. Oral thyroid replacement therapy can also cause excessive binding.

In addition, conversion from the inactive T4 molecule to the active T3 molecule should be considered as a possible source of hypothyroid symptoms. Factors that inhibit the 5’deiodinase enzyme that converts the T4 to T3 include stress or lack of selenium, zinc and a number of other vitamins and minerals.

Even when production, binding, and conversion are not the issue, the free T3 hormone must be properly transported within the cell and the receptors must respond to receive optimal benefit and management of symptoms. Factors which affect transport, receptor density and receptor response include cortisol, ferritin, and Vitamin D. Chronic high or low cortisol decrease thyroid receptor response. Ferritin should be in a range of 90-110 ng/ml and Vitamin D in a range of 60-80 ng/ml to get optimal thyroid response.

Often there are multiple sources of problems causing symptoms of hypothyroidism, and many can be addressed without the need for TRT. If TRT is administered when it is not really needed, the result may be a temporary improvement in symptoms the first few weeks, followed by a return of symptoms. The cause is the body increasing Thyroid Binding Globulin (TBG) in response to the thyroid it doesn’t really need, and therefore binding up hormone it considers excessive. The increase in TBG can take place over 2 to 3 months, so the net effect of any initiation or change in TRT is not really seen immediately.

One more problem that may cause symptoms of hypothyroidism is autoimmune reactions or heavy metal toxicities that damage the cells of the thyroid gland. Autoimmune reactions are the number one cause of all thyroid conditions. Thyroid tests should therefore always include at least one test to check for autoimmune antibodies. These tests include Thyroid Peroxidase antibody (TPO or TPOAb), Thyroglobulin antibody (TgAb), and Thyroid stimulating hormone receptor antibody (TRAb). I prefer to use TPO, as it appears to identify a reaction most commonly. If autoimmune reaction is suspected, all three tests can be ordered. Heavy metal toxicity tests can also be ordered if systemic symptoms indicate.

For more information about hypothyroidism refer to my article Differentiation and Treatment of Hypothyroidism, Functional Hypothyroidism, and Functional Metabolism.

Jim Paoletti, Pharmacist, FAARFM
7-5-2009

Timing of TRT and Interpretation of Thyroid Levels

2009-08-07T15:51:00.000-07:00

A critical aspect in interpretation of thyroid levels for a patient on Thyroid Replacement Therapy (TRT) is the timing of the sample vs. the timing of the last dose of TRT.

If the patient has not taken a dose that day, and it’s been at least 24 hours since the last dose, the levels do not represent those caused by therapy, but more of the endogenous baseline production from the gland.

For immediate release products (all manufactured products), the T4 peaks in most individuals in 2-4 hours. Levels start dropping back to baseline in 18-20 hours after the last dose. T3 peaks in 1 to 1.5 hours, and begins dropping to baseline levels in 4-6 hours in most individuals.

When you test, you want to see the “level” response, and avoid peaks or troughs. Therefore, if testing a patient on T4 therapy, it is best to test 4-16 hours after the last dose of medication to get the best correlation of levels produced by the TRT. With T3, the best time to test is 1.5 to 4 hours. For desiccated thyroid (Armour and others), which are combinations of T3 and T4, you should test 4 hours after the last dose. Any sooner could produce a peak of T4 and any later could produce a drop off from the T3. Any repeat test should use the same timing as previous testing.

So when you test compared to the last dose depends on what you want to look at. If you want to see baseline thyroid gland production, skip any dose the morning the sample is taken. If you want to see levels correlated well to the dosing, follow the above recommendations.

Jim Paoletti, Pharmacist, FAARFM
7-5-2009