HRT - AN ANTI-AGING PHYSICIAN'S PERSPECTIVE
- Dr Craige Golding MBCHB, FCP(SA), ABAARM, FAAFM
" Today's truth is this : There is no magic hormone or combination of
hormones that can be indiscriminately used by all women. Each women is an
individual and hormonal balance must be the ultimate goal for all women" -Joseph
Collins , M.D
What do we know about the non-bioidentical synthetic hormone replacements?
The government sponsored women's health initiative program halted its study on
estrogen plus progestin (synthetic progestin plus conjugated horse estrogen on
july 9 2002. This was three years early because of an increased risk of breast
cancer in women taking these hormones.[1] Analysis of the study also
revealed that heart attack risk began increasing in the progestin group early in
the study which was conducted on 16000 women who had not had a hysterectomy.
Participants in the study were either given conjugated horse estrogens plus a
synthetic progetin or a placebo.
The study revealed the following results [1]
- The stroke rate was 41% higher.
- The rate of blood clots doubled.
- Breast cancer risk increased by 26%.
- Risk of heart disease went up by 22%.
- There was a 37% decrease in colorectal cancer.
- A decrease in fracture rate of the hip of 33%
- A decrease in total fracture rate of 24%
Additional studies, such as Heart and Estrogen/Progestin Replacement Study (HERS
II) agree with the findings of the women's health initiative trial. Several
other studies have shown recently that progestins (synthetic progesterone) have
an unfavourable effect on lipid levels and may promote cardiovascular
disease[2]
Women taking
progestins show an increase in cardiovascular disease risk [3]
In defence of the pharmaceutical company manufacturing the product used in this
trial, low dose oral estrogen has been suggested instead of the much higher
doses used in the studies.
Other problems with non bio-identical synthetic hormones include :
(a) lot of women (estimated at 1/2) stop taking their hormones after 1 year due
to being unable to tolerate their side effects[4]
(b) incomplete messages are given to cells resulting in wastage of energy and
failing to produce a balanced hormonal response[5]
What do we know
about bio-identical natural hormone replenishment ?
These are some of the reasons you should consider natural hormone
replenishment/replacement :
(a) relief of menopausal or hormone deficiency symptoms.
(b) prevention of memory loss[11]. May delay the beginning and decrease the risk
of altzheimer dementia [12,13] .
(c) heart health (transdermal bioequivalent hormone replenishment DOES NOT
increase your cardiovascular risk at all.
(d) bone production (prevention of osteoporosis).
(e) growth and repair.
Natural hormone replacement means using hormones that are biologically identical
to what your body makes. Customised natural hormone replacement is the
safest way to replace hormones. Hormone replacement shouldn't be considered
without a thorough understanding of how all your body's hormones interact with
each other
"It is impossible to achieve optimum health without a properly functioning
hormonal system" - David Brownstein , MD -The miracle of natural hormones
Transdermal
delivery of estrogen is safer than oral delivery for the following reasons :
Oral estrogen can :[6] [7]
* increase blood pressure
* increase triglycerides
* increase estrone (a dangerous type of estrogen)
* cause gallstones
* elevate liver enzymes
* decrease growth hormone (the hormone that keeps you youthful)
* interrupt tryptophan metabolism and consequently
serotonin metabolism[8] (serotonin
keeps you happy and calm)
* increase sex hormone binding globulin (can decrease testosterone)
* increase carbohydrate cravings[9]
* increase weight gain9]
NOTE :
1. estrogen has more than 400 crucial functions in your body, you need estrogen for optimal health.
2. The amount of estrogen you have is important, too little or too much can cause symptoms.
3. Synthetic estrogen is not the same chemical structure of estrogen that your own body makes.
4. Synthetic estrogen takes longer to be eliminated from your body.
5. Synthetic estrogens have coatings and additives which may cause problems.
6. Mentioned earlier was the cardiac risk associated with progestins.
The following
effects are seen with natural progesterone, not seen with progestins[10]:
a) helps balance estrogen.
b) leaves your body quickly.
c) helps you sleep.
d) natural calming effect.
e) lowers high blood pressure.
f) helps your body use and eliminate fats.
g) lowers cholesterol.
h) may protect against breast cancer.
i) increases scalp hair.
j) normalizes libido.
k) helps balance fluid in the cells.
l) increases the beneficial effects of estrogens on blood vessel dilation in
atherosclerotic plaques.
m) has an anti-proliferative effect (decreases the rate of cancer) on all
progesterone receptors.
n) does not change the good effect estrogen has on blood flow.
o) increases metabolic rate.
p) natural diuretic.
q) natural antidepressant.
It is clear that natural progesterone offers a safer approach to HRT than
progestins [48]
Do you need progesterone if you have had a complete hysterectomy?
The answer is simply yes, since progesterone has many positive effects on your
body listed above.
Are there cancer issues with HRT?
Non bio-identical progesterone and non-bioidentical estrogen may increase the
risk of endometrial and breast cancer.
References
1. International agency for research on cancer.
2. J.E Rossouw "Risks and benefits of estrogen plus progestin in healthy postmenopausal women".
3. G L Anderson "effects of conjugated estrogen....".
4. C. Straczec et al
"prothrombotic mutations.......
In contrast
bio-identical progesterone and bio-identical estriol are considered protective
against breast cancer :
a) bio-identical progesterone is protective (Campagnoli C. Pregnancy,
progesterone and progestins)
b) Estriol(E3), a bio-identical estrogen, binds to the second estrogen receptor
ER beta which is a tumor suppressing receptor (Barden A, Boulle N, Lazannec ;
loss of ER beta expression as a common step in estrogen dependent tumor
progression
c) Estriol has been found to improve meopausal symptoms [45'46,47]
d) Estriol has been shown not to promote breast cancer and considerable evidence exists to show that it protects against it, and in Europe, estriol has been used for many years [14,15,16,17]
e) Estriol has even been used to treat breast cancer [18]
f) A leading
estriol researcher Henry Lemmon postulates :
..in vitro when estriol is given with estradiol, estriol accelerates removal
of estradiol bound to protein receptors
..very little carcinogenesis is initiated with estriol in animal studies
..animal studies confirm that estriol helps to prevent carcinogen-induced
mammary tumors
..estriol metabolism does not result in carcinogenic substances
Due to the possible protective effects of estriol, a combination cream such as
bi-est (estradiol and estriol) or tri-est (estrone and estradiol and estriol)
together with natural progesterone replenishment seems to be the safest way to
replenish sex-hormonal deficiencies
The metabolites of estrogen are also important in establishing your cancer risk :
a) Increased 16-OH estrone production is proposed to have significant estrogenic activity and an increased risk of breast cancer [19,20,21,22,23,24,25,26,27,28]
b) Increased 4-OH estrones also may enhance cancer development [29; 30]
studies have shown that 4-OH estrone from equine (horse) estrogen, causes mutagenic damage 5 times more rapidly than normal 4-OH estrones [30]
c) equine estrogens , increase metabolism to 4-OH estrone [30]
d) the 2-OH estrone pathway is the pathway to metabolize estrogen to have a low cancer risk
What can raise your 2-OH estrone (good) levels?
---------------------------------------------------------
1. moderate exercise [31,32]
2. cruciferous vegetables [33,34,35]
3. flax [36]
4. soy [37]
5. high protein diet [38]
6. omega 3 fatty acids [39,40].
7. vitamins b6,b12, folic acid [44]
8. indole 3 carbinol supplements [41,42,43.]
After all, the
Hippocratic Oath that all doctors sign states "first do no harm".
There is no evidence that transdermal bio-equivalent hormone replenishment does
any harm whatsoever.
Is there evidence that oral HRT can be dangerous if used AFTER the initial
period when oral HRT is mostly used to relieve symptoms? YES
(Particularly for the older group of women who are at increased risk for
cardiovascular disease)
It seems also from subgroup analysis of WHI that initially in the first few
years of taking oral estrogen synthetics, that there is an improvement in
cardiovascular risk (a decrease in coronary calcium score). However the longer
you use the oral synthetics the more likely your cardiovascular risk might
increase for reasons stated previously.
Some other thoughts ....
"The problem with popular thinking is that it doesn't require you to think at
all."
-Kevin Myers
" It is easier to do what people do and HOPE they thought it out"
-John Maxwell
"Until we can get used to living with something that is not comfortable we
cannot get any BETTER" -John Maxwell
"Courage is the power to let go of the familiar"
" The difficulty lies not so much in developing new ideas as in escaping the old
ones"
"even when we know the changes are going to be better for us and our patients we
don't make them because we feel uncomfortable or awkward" -John Maxwell
Dr Craige Golding
Specialist physician
MBCHB 1993 Pretoria University
FCP(SA) 1999 qualifying as a specialist physician
-ABAARM : American board certification in anti-aging and regenerative medicine
-FAAFM : Fellowship in anti-aging and functional medicine in the united states
References :
[1] Writing group for the women's health initiative investigators, "risk and benefits of estrogenplus progestin in healthy postmenopausal women" JAMA 2002; 288:321-333
[2] mayo clinic women's health source, sept 2002, p3
[3] grady, E ,et al ,"cardiovascular disease outcomesduring 6.8 years of hormone therapy", JAMA 2002 ; 288 [1]49-57
[4]ibid, laux pg 8
[5]ibid , yanick p57
[6] ibid,vliet p 224
[7]ibid,sinatra p210
[8] ibid , hays p 280
[9]pansini, f, et al., "control of carbohydrate metabolism in menopausal women receiving transdermal estrogen therapy" ann NY Academy Si 1990; 592:460-462
[10]ibid,laux,p 75-76
[11]sherwin,b , et al,"etsrogen and cognitive functioining in surgical menopausal women" ann NY acad sci 1990; 592:474-475
[12] ibid, tang p 429-432
[13] bland, j "inflammationand age-related diseases : the neurological , cardiovascular and immune connection" Nutritional improvement of health outcomes-the inflammatory disorders gig harbor, washington :health comm, inc, 1997 p276
[14] henerson, b, et al, "estrogen replacement therapy and protection from acute MI" am j obstetrics and gynecol 1988;159:312-7
[15] lemon, h, et al, "reduced estriol excretion in patients with breast cancer prior to endocrine therapy" jama 1966;196 [13]1129-36
[16] follingstad, A., "estriol, the forgotten estrogen? Jama 1978; 239[1]:29-30
[17] lemon, h, et al, "pathophysiologic considerations in the tratmnet of menopausal symptoms with estrogens : the role of estriol in the prevention of mammary carcinoma," ACTA endocrinol 1980 ; 223(supplement):17-2
[18] ibid,laux,p79
[19] fishman, j , et al, "increased estrogen 16 alpha hydroxylase activity in women with breast and endometrial cancer", j steroid biochem 1984; 20: 1077-1081
[20]micnovicz, j ,et al, "changes in levels of urinary estrogen metabolites after oral i3c treatment in humans j natl canc inst 1997; 89 910)718-23
[21] fishman,j, et al, "biological properties of 16alpha OH estrone;Implications in estrogen physiology and pathophysiology". , j clin endocrinol metab 1980; 51:611-615
[22] zhu, b , et al, is 2 methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis?" cancer res 1998; 58:2269-2277
[23] martucci,c,et al."p450 enzymes of estrogen metabolsim" pharmacol ther 1993;57 :237-257
[24] ursin , g,et al" urinary 2-OH /16 oh estrone risk of breast cancer in postmenopausal women, J natl canc inst 1999; 91:1067-1072
[25] meilahn E , do urinary oesterogen metabolytes predict breast cancer?" guersey III cohort follow up 1998 78(9): 1250-1255
[26] ibid, fishman, p611-615
[27] fishman , j ,et al , "increased estrogen 16alpha hydroxylase activity in women with breast cancer"
[28] telang, n , et al, "induction by estrogen metabolite 16 alpha oh estrone of genotoxic damage and aberrant proliferation in mouse mammory epithelial cells" j natl cancer inst 1992; 84(8):634-638
[29] yagi, e ,et al , "the ability of 4 catechol estrogens of 17b -estradiol and estrone to induce DNA adducts in syrian hamster embryo fibroblasts", carcinogenesis 2001; 22(9):1505 - 1510
[30] pish, e , et al "evidence that a metabolite of equine estrogens 4-oh equielin, induces cellular transformaation n vitro', CHEM RES TOXICOL 2001; 14:82-90
[31] de cree , c, et al, "4ohcatecholestrogen metabolism responses to exercise and training :possible implications for menstrual cycle irregularities and breast cancer ," fertil steril 1997; 67 :505-516
[32] ibid , arnot p 154
[33] fowke , j , et al "brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women" Cancer epidemiology biomarkers and prevention 2000 ; vol 9 :773-779
[34] bradlow h, et al, "long term responses of woman to I3c or a high fiber diet, " cancer epidemiology, biomarkers and prevention 1994; vol 3:591-595
[35] ibid, fowke, 779
[36] the effect of flaxseed and wheat bran consumption on urinary oestrogen metabolites in premenopausal women" cancer epidemiology biomarkers and prevention 2000;9:719-725
[37] lul "increased urinary excretion of 20h estrone but not 16 alpha oh estrone in premenopausal women during a soy diet containing soy-isoflavones" CANCER RESEARCH 2000 ; 60- 1299-1305
[38] anderson, k . "the influence of dietary protein and carbohydrate on the principal oxidative biotransformation of estradiol in normal subjects", J clin endocrinol metabolism 1984 ; 59 :103-137
[39] osborne, m ,et al "omega 3 fatty acids; modulation of estrogen metabolism and potentiation for breast cancer prevention" cancer invest 1988 ; 8:629-631
[40] bradlow , h , et al , effects of pesticides on the ratio of 16/2oh estrone : a biologic markerof breast cancer risk" environ health perspect 1995; 103(suppl 7 )147-150
[41] michnovicz, j , et al, "increased estrogen 2oh in obese women using oral indol3 carbinol" international journal of obesity 1998; 22:227-229
[42] ibid, michnovicz, J Nat canc instit p 718-723
[43] wong,g, et al, "dose-ranging study of indol 3 carbinol for breast cancer prevention", journal of cellular biochemistry1997 ; suppl 28/29 1111-1161
[44] ibid, bland, functional medicine approaches to endocrine disturbancesof aging p68
[45] heaa, k , estriol :safety and efficacy, Alern Med rev 1998; 3(2): 101-13
[46] tzay-shing , y et al "efficacy and safety of estriol repalcement" therapy for climacteric women", am J epidemiology 1994; 140 :256-261
[47]tzingourius, v, et al "estriol in the management of the menopause" ' JAMA 1978; 239:1638-1641
[48] ibid, rouzier, p13