The new paper  this week from the WISDOM trial (stopped prematurely  in Oct 2002 as a result of the  precipitous closure of the main premarin-provera prempro arm of the Women’s Health Initiative WHI) concludes that  Combined HT  (ie oral prempro) started many years after the menopause can improve health related quality of life. 


 This  trial  in UK, Australia and NZ  was identical to the 2002  (USA) cohort of the WHI – women mean age  about 63.5yrs with uterus,  treated with the xenohormones  prempro  or placebo, BMI mean about 28.3 kg –    except that in the WHI the age range was    50-79yrs ( 45% 60-69yrs; 21.5% were 70yrs plus) versus in WISDOM. age  50 to 69yrs  (74% 60yrs +).


As opposed to physiological doses of parenteral human  estrogen-progesterone HRT, apart from the obvious known risks of oral xenohormones – increased fluid retention, gallstones, breast cancer, adiposity, hepatic first pass inflammatory effect –   one striking practical  question arising from these trials is, why would  postmenopausal women- let alone women a mean of about 15 years postmenopausal – want to take hormone therapy causing breast discomfort and menstruation, and known for 30 years to promote latent breast cancer? Surely only men could  so trivialize the needs of women?


    In WISDOM, 32% discontinued for this reason (menstruation); and such OHT gave  no relief from tiredness, depression, headache, irritability or migraine, but greatly increased arrhythmia; leukorrhoea,   and breast tenderness (13% who discontinued). These figures were matched in the WHI after a mean of 5.2 yrs, when 40% of women reportedly had to see a gynecologist due to  problem vaginal bleeding on prempro  vs 6% on placebo.


The benefits of  OHT for up to 10 years (Nurses study; WHI; Oulu trial (Heikkinen ea 2006) and especially permanent conservative balanced  HRT (testosterone and thus estrogen for men, for women  testosterone-estrogen-progesterone replacement) till past 90years has been overwhelmingly  proven in long term clinics world wide (eg Greenblatt; Schleyer-Saunders; Gelfand; Whitehead & Studd; Burger & Davis; Vliet; Shippen;  Nieschlag & Behre; Carruthers, Kauffman) – all of whom have observed reduction in premature degenerative diseases in their attending patients .


       It is common cause that  even appropriate OHT- started soon after menopause- reduces all-cause major illness and mortality by one-third, even after breast cancer. By avoiding OHT, one  may reduce the incidence of breast cancer; but only about 4% of women die of breast cancer – it rarely cripples; more than half of such  women thus suffer and die prematurely from other hormone-deficiency diseases like vascular, dementing  and  osteoporotic problems, which are halved by  appropriate HRT. 

The question  is, where is the logic of commercial marketed HT that forces the postmenopausal endometrium and ductal breasts to go on proliferating cyclically? One would have thought  that doctors and women learnt their lesson by 1980  with the increase in endometrial and breast cancer on long term unopposed oral estrogen therapy – mostly premarin in USA. Physiological testosterone replacement in men does not do this to the prostate, nor to the breasts or other organs in women. .

The published trials show that unopposed transdermal estradiol gave much lower rates of endometrial bleeding than OET- but seldom none at all.. 

And recently Horwitz and Sartorius  showed that even progesterone combined with estradiol  can be the trigger of latent breast cancer. .


Yet Medline reports  plainly that William Masters and  peers had firmly recorded by the time they reported the first randomized controlled HRT trial in 1953 that parenteral (intramuscular)  testosterone TT- estradiol E2 abolished endometrial and breast problems in even older, institutionalized  women (about 20 years post menopausal)- with nothing but benefits for the majority  of the women (remarkably only one-third failed to improve). They determined by trial and error that the optimal ratio was 20:1  TT:E2 – and they persevered for a mean of 13 months with a dose of TT 20mg plus 1mg E2 esters  twice a week (ie averaging about 2.8mg TT and 0.4mg E2 a day) .

       We have followed their regime for about a decade, but using a physiological approach with only 20mg TT ester and 1mg E2 ester subcutaneously every +-  fortnight  ie about 1mg TT and 0.05mg E2 a day. W rarely have to vary this ratio or dose in young women, whereas elderly women tolerate far less, complaining of breast and pelvic  tenderness  on the youthful dose. So for those who eschew the tiny injections and can afford cream, we use a combination of about 0.125% estrogen (80% E3, 20% E2) with 1% testosterone and 0.75% progesterone for young women, and about 1/8th that strength for the elderly. We

 let women  titrate the dose to symptom and bone  improvement without unwanted symptoms. With such combination in conservative balanced doses, we find that women have no more periods, and their endometrium and breasts  remain quiescent  on followup ultrasound and mammography respectively. .


 Recently the Karolinska Institute (Zang et al)  has  confirmed that combining testosterone with estradiol reduced the proliferative effect of estrogen on the endometrium- but they ignored Masters’ and Grody’s papers of 1953, the Karlinska trial used vigorous doses of oral HT in a too-low ratio of TT 10: E2 1.


And a separate paper  (Hofling et al) from the Karolinska  also confirms the findings of Zhou and Dimitrikakis, and Thomas Clarkson’s team at Wake Forrest,  that testosterone suppresses breast proliferation in humans, rats and monkeys.

        It is common cause that the healthy young woman has an average serum TT:E2 ratio of about 4:1 (mean sTT about 1.5-2nmol/L, mean sE2 about 0.4-0.5nmol/L)- compared to in healthy lean young  men , sTT about 25-30nmol/L, sE2 about 0.1nmol/L ie >270:1- men being relatively resistant to testosterone. .


     .Exogenous unopposed estrogen promotes adiposity, thrombosis, arrhythmia, autoimmunity, inflammation  cellular proliferation, and profound vaginal collagen loss (hence doubling that rate of stress urinary incontinence) –  but  has no demonstrated benefit ie anabolic effect on mood or muscle (except the uterus) – ie the opposite effects of TT.

So  it defies logic why normally mildly testosterone-dominant young women are sentenced by most doctors- at the dictate of drug companies marketing their profitable horsepills –   to have their necessary androgen levels (both ovarian and adrenal) either naturally depleted by age and surgery, or worse, further suppressed by HT (without balancing TT), as in the case of the combined OC pill, depotprogestin injections, or postmenopausal estrogenic herbs, or estrogen +- progestin therapy- especially in 20 times higher doses widely prescribed  OHT  than are necessary parenterally. . .

        Appropriate patenteral HRT (esters of TT:E2 20mg:E2 1mg, or just TT 200mg for men) fortnightly by tiny subcutaneous self-injection need cost no more than R40 or US$5/month .  In the absense of lowdose progesterone in the injection, adding lowdose progesterone cream quadruples the cost.


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