Physiologic Restoration

WHN Physiologic Restoration uses the rhythmic dosing philosophy. We believe in developing the approach which matches most closely that of a woman’s body. As nature has rhythms, so does the body.

Humans have a complex molecular clock that regulates our physiology -- this includes hormones as well as metabolic homeostasis in general. We have an internal time-keeper that interconnects our endocrine rhythms and circadian rhythms. Taking cues from light signals, the latter regulates the sleep-wake cycle. It dips and rises like a carousel throughout the day and repeats roughly every 24 hours -- and mimics the female reproductive cycle by following a 28-day sequence. Environmental factors also play a role to either maintain or disrupt the internal balance.

Understanding these hormone mechanisms allows the WHN to develop Physiologic Restoration protocols that establish just the right doses of estradiol and progesterone to mimic that natural hormone cycle your body would produce in your 20’s. Physiologic Restoration restores the normal growth and growth modulation pattern that supports health and function in cells and tissues.

Physiologic Restoration uses a topical cream applied from an easy-to-use dispenser, in amounts that are designed to create the natural fluctuating hormone levels of a young woman. Healthy women in their 20’s, for the most part are not experiencing heart attacks, Type 2 diabetes, osteoporosis or Alzheimer’s disease.

Static Dosing

Numerous hormone protocols are delivered in what are called ‘static doses. Blood tests are taken, hormone levels are then approximated, after which a patient is prescribed estradiol and/or progesterone to be taken or applied in the same amount each day. The body does not produce hormones naturally in this way, which is why PR does not prescribe to this philosophy. In addition, though statically dosed hormones can ease symptoms, it doesn’t address the root cause of the problems or lower the potential for risks of disease which rhythmic dosing is known for accomplishing.

Static, simultaneous dosing is the template of Big Pharma’s synthetic PremPro, which has been proven by the Women’s Health Initiative Study to be very dangerous on many levels. Administering estrogen and progesterone, even bio-identical compounds, in a static non-mimetic dosing schedule is not physiologic in healthy, fertile women.   Some physicians recognize the need to have some fluctuation in the course of a month. Until we have the long term studies to show which pattern is most beneficial, it seems most reasonable to stay with nature’s pattern, the one that occurs in the healthiest years. By giving static doses of hormones we are not allowing optimal progesterone receptors to be produced which results in inadequate cell apoptosis and a higher chance of breast cancer initiation and recurrence. There is data showing that chronic administration of progesterone/progestins will down regulate specific P4 receptors.

Low dose P4 can’t be accurately measured in serum at this time. The salivary standards currently used were specifically designed by the lab working with Dr. John Lee at the time to justify his dosing premise of “Estrogen dominance” aka, lack of progesterone, in peri and post menopausal patients and not as an accurate baseline in healthy young women. Serum levels of young fertile women have been recorded for decades which are the case for using serum levels to monitor.

On cyclic hormone therapy appropriate labs and a detailed history and review of systems should be measured every three months during the first year to ensure therapeutic symptomatic and physiologic optimums are achieved. Using suboptimal dosing may produce suboptimal results without knowing or experience best results possible. It is important to keep in mind that what is topically applied is not all absorbed. In clinical practice when I have tried to wean women off Premarin and start topical standard pharmaceutical transdermal estrogen, the patients could not tolerate the symptoms and requested to be put back on the Premarin. The topical estrogen was not absorbing well enough, nor a high enough dosage to produce the same effects as the oral premarin. Oral estrogen (Premarin) does account for likely increase of SHBG.

During the years a woman’s ovaries are healthy, her body is in balance. Every system in her body is functioning and turning over at an optimal rate. Mind and body are at their best and she is fertile. This state of vitality and health is largely due to the intelligent rhythm that nature created. It is not fool proof, as we see in many women who have suboptimal ovarian function. The state of well being begins to decline as women approach menopause. Cycles become anovulatory, progesterone is deficient, estrogen levels wane and the hormonal rhythm and balance is lost. Several chronic diseases are now being attributed to low estrogen levels (arthritis, osteoporosis, cardiovascular disease, etc). By trying to restore nature’s rhythm we can approach the optimal function that healthy ovaries provide. Again, sex steroids are dose dependant in their results. We can’t really know the optimal amount or serum level of either estradiol or progesterone in a postmenopausal woman….since it is very little in a natural state.

A healthy, well-functioning fertile woman produces estradiol in a distinct rhythm throughout her menstrual cycle. By its rhythmic production, estradiol up-regulates its own receptors, progesterone receptors, and multiple other hormone receptors including growth hormone receptors. To optimize estrogen’s activity throughout the body and optimize progesterone and other hormone receptor production seems logical and important to reproduce the ovarian rhythm as closely as possible. A small amount of progesterone is normally produced by the adrenal gland throughout the month. A small amount is also thought to be produced by the ovaries or the brain throughout the month.

Adding significantly more progesterone during days 1-13 is not physiological and can be counterproductive.   More progesterone than what the receptors can accept can cause excess progesterone to convert to cortisol leading to other concerns.  Persistent progesterone can down regulate certain progesterone receptors necessary for normal functions.  Women who have healthy adrenals should maintain the natural ovarian cycle and replace progesterone when the cells have been maximally primed for it.  There are no long-term studies to compare static dosing vs. rhythmic dosing.

However, until rigorous long-term studies are performed it is logical and scientifically sound to reproduce and replace what the brain and ovaries have produced in their healthiest years.  Some women feel well on progesterone throughout the month.  These women are likely to have compromised adrenal function.  There is more than one way of dealing with stressed adrenals, but as with most such cases in advanced medicine it is better to address the underlying cause.

The estrogen produced by the human ovaries is estradiol. Some estrone is produced from the conversion of androgens from the adrenal glands and from fat stores for the postmenopausal woman. Estrone is also converted from estradiol. Whatever limited data there is on estrone indicates that estrone is the least favorable estrogen. Limited data has linked it to breast cancer, but it may be that most of the breast cancers (2/3) occur in postmenopausal women after age 55. There is no logic in supplementing it. Estriol is a non-reversible metabolite of both estradiol and estrone. Estriol may have beneficial effects in the urogenital system (bladder and vaginal tissues).  Estradiol eventually converts into estriol; so there is no point of supplementing the metabolite.

Julie Taguchi, an Oncologist in Santa Barbara is active with clinical oncology research through UCLA, and is an associate professor of clinical medicine with USC. She has shown, based on a small observational study within her own practice, that women have better quality of life without an apparent significant increase in recurrence or new breast cancers. Long term data with large numbers of patients is not available but is needed to accurately evaluate the risk of breast cancer or recurrence. Unfortunately, this is unlikely to happen in the current medical practice. Many physicians are reluctant to help women based on the lack of data but soon realize that women are less reluctant than their physicians to be on cyclic hormone replacement therapy because it makes sense. Once a woman starts to feel better, she will do anything to continue feeling that way.

The uterus is a barometer, indicating how the rest of the body is functioning. A normal menstrual cycle indicates to the brain that the body is fertile, which is an optimum state of health. To have a uterus and be on hormones and not have a period just means lack of optimal function. We really do not know what the long term consequences of this are. Until long-term studies are done it is up to the patient and the physician to decide which approach to take. When women have hormones they have periods. When women are postmenopausal with little or no hormones, there are no periods. Something in between is not physiological or biological and is unknown.

The majority of women begin to feel the hormones start to make a difference in the first three months, some even feel incredible after the first month. The goal of Physiologic Restoration is to create estradiol and progesterone receptors and fill them by reaching physiological levels of these hormones.

During the first month some of the estradiol is received. By month two, almost all of the estradiol should be fully received and most of the progesterone since It takes estradiol to create the progesterone receptors. After month three we might assume that full receptor complement is complete. If your breasts become tender, this is when they will feel much better.

It is now appropriate to do lab tests on days 12 & 21, to justify dosage increases of estradiol or decrease progesterone, to individualize the protocol. This entire process on average can take up to a year to titrate and adjust to restore hormones back to youthful, physiologic levels. But every month is better than the month prior.

The minimum (initial) dose of Physiologic Restoration is actually the least amount needed to show consistent clinical improvement or even approach the bottom of the reference range in blood work for healthy young women.

The only women that might be eligible for lower dosing, are women who have never had exogenous hormones and it's only recommended for one month. Remember, the estrogen peak on day 12, is provoking the progesterone receptor for the luteal phase.

Your provider should be able to modify your dosage based on your physical response when you begin the protocol, and make appropriate adjustments to your dosing.

It's not one size fits all, it's one size starts all.

Estradiol is normally metabolized into estrone. It’s a precursor before E3 (estriol) .People think that estrone is carcinogenic but it’s not as long as progesterone is given. Estrone is a predominant estrogen in postmenopausal women. The PR protocol uses plenty of progesterone.

Our modern calendar (Julian calendar) is an artificial measure of time instituted by the Romans to stamp out Paganism and any other culture acknowledging Moon Time. Our bodies did not evolve in Roman times. We have lived in cosmic time for 13.7 Billion years as coalescing particles with the ultimate emergent property- life. So we evolved the hormones that report our veritable existence in the soup on cycles of the moon and sun and stars and we will, therefore; attempt accurate replacement using those markers as place holders to keep us from flying off this earth. (Wiley)

Some Questions contributed by
Gretchen Jones, PA-C, Hormone Specialist and Internal Medicine

The goal of WHN is to expand the Standard of Care by promoting, advocating, and advancing women's wellbeing and longevity through clinical research and education about the benefits of Physiologic Restoration to reduce the symptoms of hormone imbalance, chronic disease and degenerative decline.
WHN is a registered 501(c)3 not-for-profit corporation