Only giving estrogen without progesterone is NEVER a good idea. A healthy woman between menarche and menopause
produces a monthly cyclical change in her hormones, most notably estrogen, progesterone, and testosterone.
Prescribing both estrogen and progesterone replacement simultaneously
without alternation is the current standard of care. However, doing so is like driving down the road with one foot on the gas
and the other simultaneously on the brake. This is NEVER a natural solution, even if bio-identical hormones are used.
This dosing schedule ever creates anything close to a natural physiologic state.
Varying hormone replacement to match a young woman's (age 25) hormone cycle (e.g. the Wiley Protocol) arguably reproduces a more natural physiologic state,
but may have the side effect of producing menses just as seen in a young woman - which some consider to be unnatural itself.
Ultimately, each individual woman should have the right and responsibility to choose the hormone replacement strategy that makes most sense to her.
Dr. Weyrich is trained in the use of bio-identical hormone creams according to either fixed (conventional) or cyclic (Wiley) protocols, and is
happy to discuss the risks and benefits of each protocol.
It has been observed that women being adequately treated for hypothyroidism have far fewer
menopausal symptoms than those in the general population [Barnes],
[
Starr2005, pg 149].
Current medical thought is that it is best to institute hormone replacement therapy
(HRT) soon after menopause for maximum benefit at lowest risk.
Some controversy regarding HRT for menopausal symptoms was raised by the
Women's Health Initiative Study (WHI) [Rossouw2002], which found a slightly increased risk of heart
attack, stroke, and breast cancer for certain groups of women using the non-bioidentical
hormones Premarin and Provera,
despite considerable benefits and the reduction of risk in other groups.
[Quigley2006] has pointed out flaws in the design of the study. In addition, the risks attributed
to the non-bioidentical hormones Premarin and Provera may not extrapolate to the
bioidentical analogs made endogenously by women and available from compounding pharmacies
[Quigley2015],
[Starr2005, pg 194],
[Brownstein2003],
[Vliet2000].
Research has shown that starting estrogen replacement therapy (ERT) in perimenopausal or early-menopausal women reduces the risk of a heart attack
by 30-50%, by protecting against arteriosclerosis. However, if start of ERT is delayed more than 6 years after menopause, this protection is lost.
Furthermore, synthetic progestins (but not bio-identical progesterone) reduce the benefit. Furthermore, as shown by the Women's Health Initiative
(WHI),
Starting HRT in older (50-79 years old) women causes a SLIGHT increased risk of heart attack, breast cancer, stroke (not statistically significant),
and venous thromboembolism. Nonetheless, the benefits of HRT have still been shown to outweigh the risks. For example, in the 50-59 year old
Premarin-only cohort, heart attacks were reduced by 44%, invasive breast cancer by 28%, all-cause mortality by 27%). All these benefits more than
compensate for the increased risk of thromboembolism (22% increase) in that same cohort.
[Quigley2006],
[Quigley2015],
[Rossouw2002],
[Wassertheil_Smoller2003].
The WHI study has also been criticized on a number of points, including:
- Benefits of HRT were lost by not starting at age of onset of menopause
- No adjustment of dose for age (rate of drug clearance)
- Subjects had many comorbidities but most did NOT have menopausal symptoms
- Use of synthetic progestin instead of bio-identical progesterone
[
Quigley2006],
[
Quigley2015].
In addition to the benefits of testosterone supplementation in preventing (and treating)
breast cancer,
[Glasser2011] has shown that testosterone supplementation benefits menopausal symptoms.
However, [Janssen2010] has shown
that as estrogen levels drop in perimenopause and menopause, SHBG also decreases, resulting in an effective increase in bioavailable testosterone,
which is in turn associated with an increase in insulin resistance and visceral fat. [Dr. Weyrich notes association does not
prove cause and effect]. See also [Sutton_Tyrrell2005], [Lee2004], [Zang2006], [Lambrinoudaki2006].
[Golden2007] concludes "of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG
was negatively associated with insulin resistance."
[Matsui2013]
states "SHBG may be a key factor related to insulin resistance independent of estradiol and testosterone"
and an "estradiol level that is comparable to that in premenopausal women may be needed for improvement of
insulin sensitivity by hormone therapy in postmenopausal women" (in their study, postmenopausal women receiving
supplemental estrogen had lower circulating estrogen levels than premenopausal women). These authors also raise the question
of whether the SHBG is directly involved in insulin resistance, [Dr. Weyrich: and free testosterone is simply a marker of low SHBG].
Since the optimum level of estradiol and testosterone to reduce cancer risk and
menopausal symptoms without increasing insulin resistance and visceral fat has not been established, testosterone should only be supplemented
when free testosterone is below normal physiological levels for premenopausal women, and insulin resistance and visceral fat should be monitored.
This begs the question of what optimal hormone levels of estradiol, progesterone, testosterone, and DHEA are for postmenopausal women.
Opinions vary from "let nature take its course" to "supplement with the minimum levels necessary to eliminate symptoms" to
"reproduce the hormone profile of a 20-year-old woman." The available data clearly shows HRT is superior to letting nature take its course,
but Dr. Weyrich finds insufficient data in the literature to evaluate the merits of the latter two options (or more properly, the continuum between
the latter two options). The only thing that is clear is the approach to HRT must balance all hormones.