Category Archives: sex

29 SEPT 2014 OVARIAN CANCER UPDATE: PROGESTERONE REPLACEMENT IS IDEAL; WHY USE ORAL HT? WHEN ESPECIALLY LONG TERM PROGESTINS GREATLY INCREASE RISK OF OVARIAN AS WELL AS BREAST CANCER.

: ABSTRACT:  since last review in  this column 5 years ago, what progress has there been with ovarian cancer OvCa? On Pubmed there are 81000 references,  45500 reviews on OvCa

5 Oct 2014:  Ovarian Cancer Often Arises from Precursor Endometriosis    Frontline Medical News, 2014 Sep 29, B Jancin

   29 Sept 2014  The good news is that if ovariectomy is not done at hysterectomy, then at least salpingectomy should be done- it does not cause earlier menopause.  And the modern fashion for progesterone cream as baseline hormone balancing in this age of estrogen dominance, the feminization of nature,  also adds major protection for heart, bone, memory, mood,  and against cancer, without the risks of estrogen.

Before this month’s update,  the latest, an Australian cancer review  Mette ea 2013, shows that cigarette smoking increases the risk of OvCa by 30% to 60%.

The latest   review 2013 Modugno ea at Univ Pittsburgh/Mayo Clinic  Hormone response in ovarian cancer: time to reconsider as a clinical target?   said “Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence from in vitro studies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response.The most consistently reported reproductive and hormonally related factors found to protect against EOC are use of oral contraceptives (OCs), increasing parity, and having a tubal ligation. In contrast, increasing age and nulliparity have been consistently shown to increase EOC risk. 

    Recent studies, including the prospective Women’s Health Initiative (WHI) (Anderson et al. 2003) and the Million Women Study (Beral et al. 2007), report an increase in risk for both estrogen-only (ET) and estrogen–progestin (EPT) formulations, although the risk associated with EPT was lower than that of ET. A recent meta-analysis of 14 published studies found risk increases 22% per 5 years of ET use compared with only 10% per 5 years of EPT use, suggesting that risk differs by regimen (Pearce et al. 2009).               Exogenous androgens may be associated with EOC. One case–control study found that use of Danazol, a synthetic androgen commonly used in the treatment of endometriosis, significantly increased EOC risk (Cottreau et al. 2003), although this finding has not been replicated (Olsen et al. 2008). Ever use of testosterone (tablets, patches, troches, or cream) has been associated with a threefold increase in EOC (Olsen et al. 2008).             

     Reproductive disorders and other reproductive factors :  Factors affecting childbearing have also been shown to be associated with EOC. In most studies, infertility has been associated with an increased risk, which may be greatest among women who fail to conceive (Vlahos et al. 2010). In general, infertility treatment does not appear to increase EOC risk, although the subset of treated women who remain nulliparous may be at an increased risk (Vlahos et al. 2010).

         Endometriosis, defined as the presence and growth of endometrial tissue outside the uterine cavity, has also been associated with EOC. A recent pooled analysis of 13 case–control studies showed a threefold increase in the incidence of clear cell EOC and a twofold increase in endometrioid EOC among women with a self-reported history of endometriosis (Pearce et al. 2012).

    An increased risk of EOC was reported by one case–control study (Schildkraut et al. 1996) among women with polycystic ovary syndrome (PCOS), a condition associated with menstrual dysfunction, infertility, obesity, the metabolic syndrome, hyperandrogenism, and insulin resistance. However, the finding was based on a small number of cases (n=7) and the association was limited to nonusers of OCs and thin women. Further case–control and prospective studies have failed to confirm this relationship (Pierpoint et al. 1998, Olsen et al. 2008, Brinton et al. 2010).

   Tubal ligation has been consistently shown to be associated with reduction in EOC risk (Cibula et al. 2011). This protection appears similar in magnitude to OC use and child bearing (about 30%) and is protective in high-risk women (i.e. BRCA1/2 carriers) as well. Hysterectomy has also been shown to reduce EOC risk, although the magnitude of the association is not as great nor as consistent as that reported for tubal ligation (Riman et al. 2004). Finally, reproductive factors associated with other hormonally linked cancers, such as age at first menarche, age at menopause, and length of reproductive years, have not been consistently associated with EOC (Riman et al. 2004).

    Estrogens and androgens –  The evidence linking these  to EOC are mixed. The majority of women who develop ovarian cancer are postmenopausal at the time of diagnosis. In postmenopausal women, the major source of circulating estrogen is from the peripheral conversion (in skin and adipose tissue) of androstenedione by the enzyme aromatase.

    Progesterone and progestins- Epidemiological data suggest that progestins and progesterone may have a protective role against EOC. Importantly, there is some evidence that progesterone might synergize with chemotherapeutic drugs to induce apoptosis.

Now this month  comes exciting news about  a  Paradigm Shift: Prophylactic Salpingectomy for Ovarian Cancer Risk Reduction   Frontline Medical News, 2014 Sep 24, B Jancin     :   Removing the fallopian tubes at the time of pelvic surgeries as a potential means of reducing ovarian cancer risk appears to be a movement that’s picking up steam in clinical practice.
       A recent survey of 234 U.S. gynecologists showed prophylactic bilateral salpingectomy is catching on when performed in conjunction with hysterectomy, but far less so for tubal sterilization, Dr. Austin Findley observed at the annual Minimally Invasive Surgery Week.                                                                       A total of 54% of respondents indicated they routinely perform salpingectomy at the time of hysterectomy in an effort to reduce the risk of ovarian cancer as well as to avoid the need for reoperations. However, only 7% of the gynecologic surgeons said they perform salpingectomy for tubal sterilization, even though 58% of respondents stated they believe the procedure is the most effective form of tubal sterilization (J. Minim. Invasive Gynecol. 2013;20:517-21).
  “In my experience at various hospitals, I think these numbers are a pretty accurate reflection of what folks are doing,” commented Dr. Findley of Wright State University in Dayton, Ohio.
     The prophylactic salpingectomy movement is an outgrowth of the tubal hypothesis of ovarian cancer.
    “There is now increasing and dramatic evidence to suggest that most ovarian cancers actually originate in the distal fallopian tubes. I think this is a concept most people are unaware of or are just becoming accustomed to. The tubal hypothesis represents a major paradigm shift in the way we think about ovarian cancers. The previous belief that excessive ovulation is a cause of ovarian cancer is no longer regarded as accurate,” he explained at the meeting presented by the Society of Laparoscopic Surgeons and affiliated societies.
      Ovarian cancer is the No. 1 cause of mortality from gynecologic malignancy, accounting for more than 14,000 deaths per year, according to National Cancer Institute data. The lifetime risk of the malignancy is 1.3%, with the average age at diagnosis being 63 years.
       Only 10%-15% of ovarian cancers occur in women at high risk for the malignancy because they carry a BRCA mutation or other predisposing gene. The vast majority of ovarian cancer deaths are caused by high-grade serous tumors that have been shown to be strongly associated with precursor lesions in the distal fallopian tubes of women at low risk for the malignancy.
            There is no proven-effective screening program or risk-reduction method for these low-risk women. However, with 600,000 hysterectomies and 700,000 tubal sterilizations being performed annually in the United States, prophylactic salpingectomy has been advocated as an attractive opportunity to potentially reduce ovarian cancer risk. Other common pelvic surgeries in which it might be used for this purpose include excision of endometriosis and laparoscopy for pelvic pain. It also has recently been shown to be feasible and safe post partum at cesarean or vaginal delivery (Obstet. Gynecol. 2014 [doi: 10.1097/01.AOG.0000447427.80479.ae]).
   But the key word here is “potentially.” It must be emphasized that at present the ovarian cancer prevention benefit of prophylactic salpingectomy remains hypothetical; in theory, the procedure should reduce ovarian cancer risk, but there is not yet persuasive evidence that it actually does, Dr. Findley emphasized at the meeting, presented by the Society of Laparoendoscopic Surgeons and affiliated societies.
            In contrast, one well-established ancillary benefit of prophylactic salpingectomy is that it eliminates the need for future reoperation for salpingectomy. This was demonstrated in a large Danish cohort study including close to 10,000 women undergoing hysterectomy and a similar number undergoing sterilization procedures. Among the nearly two-thirds of hysterectomy patients who had both fallopian tubes retained, there was a 2.13-fold increased likelihood of subsequent salpingectomy, compared with nonhysterectomized women.
        Similarly, Danish women who underwent a sterilization procedure with retention of the fallopian tubes – typically tubal ligation with clips – were 2.42 times more likely to undergo subsequent salpingectomy, most often because of the development of hydrosalpinx, infection, ectopic pregnancy, or other complications (BMJ Open 2013;3 [doi:10.1136/bmjopen-2013-002845]).
     The most commonly cited potential risk of prophylactic salpingectomy – decreased ovarian function – now appears to be a nonissue. This was demonstrated in a recent retrospective Italian study (Gynecol. Oncol. 2013;129:448-51) as well as in a pilot randomized controlled trial conducted by Dr. Findley and his coworkers (Fertil. Steril. 2013;100:1704-8), which appears to have answered many skeptics’ concerns. Indeed, Dr. Findley’s coinvestigator Dr. Matthew Siedhoff said he has recently been approached by researchers interested in collaborating in a larger confirmatory randomized trial, but all parties eventually agreed it was a no-go.
    “It’s a little hard to demonstrate equipoise for a larger randomized controlled trial. We’re beyond that now, given that prophylactic salpingectomy really doesn’t seem to make a difference as far as ovarian function,” according to Dr. Siedhoff, director of the division of advanced laparoscopy and pelvic pain at the University of North Carolina, Chapel Hill.
         Another oft-expressed reservation about salpingectomy as a means of reducing ovarian cancer risk in women seeking sterilization is that salpingectomy’s irreversibility may lead to “tubal regret” on the part of patients who later change their mind about further pregnancies. However, Dr. Findley cited a recent editorial whose authors criticized colleagues who made that claim. The editorialists argued that the tubal regret concern indicates surgeons weren’t really listening to their patients’ true desires during the informed consent conversation.
     “We should not have started thinking about salpingectomy for female sterilization only once a decrease in ovarian cancer risk became part of the equation,” they declared (Obstet. Gynecol. 2014;124:596-9).
           Dr. Findley noted that Canadian gynecologists are leading the way forward regarding prophylactic salpingectomy as a potential method of ovarian cancer prevention. The Society of Gynecologic Oncology of Canada in a 2011 policy statement recommended patient/physician discussion of the risks and benefits of bilateral salpingectomy for patients undergoing hysterectomy or requesting permanent sterilization. The Society of Gynecologic Oncology followed suit with a similar clinical practice statement in late 2013.
        Additionally, the Canadian group declared that a national ovarian cancer prevention study focused on fallopian tube removal should be a top priority.
    Gynecologic oncologists in British Columbia recently reported the eye-catching results of a province-wide educational initiative targeting gynecologists and their patients. In 2010, all British Columbia gynecologists had to attend a course on the role of the fallopian tubes in the development of ovarian cancer, during which they were advised to consider performing bilateral salpingectomy for ovarian cancer risk reduction.
              Surgical practice changed dramatically in British Columbia in response. In 2009 – the year prior to the physician education initiative – salpingectomy was utilized in just 0.3% of permanent sterilization procedures. In 2010, it was 11.4%. By 2011, it was 33.3%.
           Similarly, only 7% of hysterectomies performed in British Columbia in 2009 were accompanied by bilateral salpingectomy. This figure climbed to 23% in 2010 and jumped further to 35% in 2011. Meanwhile the rate of hysterectomy with bilateral salpingo-oophorectomy remained steady over time at 44% (Am. J. Obstet. Gynecol. 2014;210:471.e1-11).
     This project was conducted in collaboration with the B.C. Cancer Agency, which maintains comprehensive province-wide registries. Over time, it will be possible to demonstrate whether prophylactic salpingectomy is indeed associated with a reduction in the incidence of ovarian cancer. “I think this study demonstrated that there’s a lack of awareness on this issue, but also [that there’s] potential effectiveness of introducing an educational initiative like this in changing our practice patterns. As we start talking more about this issue amongst our colleagues and our patients, we’re more likely to see a practice pattern shift in the United States as well,” Dr. Findley commented.

17 July 2009     A new cancer study of  over 7 million women years is another major coffin for unopposed estrogen ET, for progestin Pg, and for oral  sex hormone therapy SHT.

Danish  Universities prospectively document  the incidence of ovarian cancer OvCa in a million postmenopausal women PMW  from 1995 through 2005.  Compared to non-users, use of HT increased OvCa (mean age 62yrs) by about 40%   for up to 2 years after stopping Ht, ie increased the absolute incidence  of clinically diagnosed OvCa from ~ 0.04 to ~0.052% ie per 100 patient yrs.

Transdermal TD ET alone  increased risk by 13%; vaginal ET by 23%;                                            Oral ET alone increased  risk by  34%; oral E+ progestin Pg by  48%;          TDE+Pg by 67%.

Thus the relative incidence of OvCa rose about 33% by 7 years on HT, to 48% if HT continued beyond 7years.

In 2004 Glud ea reported an increase risk of 31% for OvCa in Danish women on OHT use – total ET dose of ~5gm ie for about  for 15yrs – at a time when the standard premarin  dose was 0.625mg/d (equivalent to l mg E2)  if not double that .

For perspective,  the relative incidence of cancers in similar mostly 1st world European women from the  the USA SEER data for 2006 age over 50  years  are: BrCa 0.33%,  uterus 0.07%, ovary o.03%(ie very similar to the baseline Danish figure of 0.04% above), colon 0.15%,and cervix 0.01%. The new (Norwegian)  analysis in the latest BMJ suggests that screening mammography may result in overdiagnosis of BrCa by up to 50% (the other 50% may arguably never have been clinically significant-diagnosed- during life) , so the provocative could argue that the relative incidence of clinically significant BrCa to OvCa is more like eg BrCa 0.2 to ovary 0.03 ie just below 10:1. But OvCa is notoriously about 70% fatal within a few years, so  the absolute  mortality rate – at age 60-64yrs-  from  the same SEER  source and period are as relevant: BrCa 0.063%, uterus 0.011%, ovary 0.033%, colon 0.03% & cervix 0.005%. ie new OvCa may be only 1/10th as common as newBrCa, but BrCa  kills only twice  as many PMW as OvCa.

And finally the 2007  survey by  Rossing ea of  Menopausal Hormone Therapy and Risk of Epithelial Ovarian Cancer in women in Washington State 2002-2005 showed that  ET -mostly premarin (but not ET + progestin- MPA medroxyprogesterone provera) – especially in  low-parity  younger slim women increased OvCa compared to non-users, and that this risk  was highest- up to 90%-  in  users of OET  for more than 6 years.

By comparison – BREAST CANCER BrCa and HT: Hoover ea  1976  are the first on Pubmed to report doubling in  risk of breast cancer  BrCA after 15yrs on premarin in USA ie at least 5gm cumulative dose.

In Denmark by 1994 Ravn ea reported that if there was a risk of BrCa from OHT, it was small, and only after prolonged use of estrogen (15-20 years).  But by 2004 -2005 Tjønneland ea , Stahlberg ea  and Ewertz ea  found increased risk for BrCa  of 61 to 112%  associated with current use of HT.  Stahlberg ea already in 2003 concluded from recent studies from both the USA and Europe that the combined treatment regimens with estrogen and progestin increase the risk of BrCa  beyond the risk of unopposed estrogen.

In Norway, a recent Tromso study suggested that the dominant HT therapy used in Norway was oral estradiol E2 plus the progestin norethisterone acetate. . An earlier Tromso study in only 35000 PMW was too small- it showed that use of such OHT for >5yrs trebled the incidence of breast cancer BRCa, but did not influence that of OvCa.

Apart from smokers’ lung cancer, the commonest cancer in older women- BrCa- clinically affects perhaps 5% of PMW  lifelong – but  with prompt therapy after clinical presentation kills as few as 5% of sufferers- and with appropriate OHT (premarin +- provera)  for up to 8years in the Women’s Health Initiative both the incidence of and mortality from BrCa, and all-cause mortality,  were reduced by about one-third. Hence appropriate HT saves many from both BrCa and from premature death and disability from the commonest degenerative diseases- vascular, dementing and fracturing. 75% of women who develop BrCa  die with it –  not from it but from far more prevalent degenerative diseases after an  otherwise normal lifespan. But the Danish evidence is that combined OHT will increase OvCa by >50%.

Ovarian Ca kills 70% of victims, and is it so rare compared to BrCa? .

Hence with the perhaps 2/3  lower incidence of OvCa, it is a relatively trivial problem for women overall- except for the 4  in  10 000 women  who develop it, who have <50% 5year survival, ie 3 out of 4  of whom it will kill within a few years- compared to <25% of breast cancer victims who will be killed by the BrCa.

However, it becomes clear that these hormone-dependent cancers are both  duration-  and total-dose HT related; but even more important, that unopposed OET is a risk if persisted more than about 12 yrs; and even if used in far lower dose parenterally, the risk of OvCa is far higher if combined with the European fashion of androgenic synthetic progestins Pg – even parenterally; whereas the American MPA for up to 8years at least apparently if anything mitigates the OvCa risk of ET..

By contrast this column has repeatedly reviewed evidence that balancing physiological ERT with physiological testosterone replacement TRT eliminates the risk  for BRCA and endometrial cancer of unopposed ERT +- PRT in PMW.  Intuitively this should also apply to ovarian cancer.

Hence the message strengthens that PMW should not be exposed for  any length of time at any stage to the much higher oro-hepatic HT doses (needed for symptom control) or OET+- Pg; but as in all other endocrine replacement for permanent  multisystem prevention – let alone sexual function-  patients with gonadal deficiency should have physiological sexhormone balance restored  ie with balanced parenteral  human androgen, estrogen and progesterone replacement.

It is common cause that (reproductive cycles and pregnancy aside) all the physiological  prime sex hormones-DHEAdehydroepiandrosterone, P4, T, E2, E3 – are as important as all other human hormones, essential life long  for optimal health; and that estrogen dominance (due to inadequate  androgen and progesterone levels) is deleterious. Hence most PMW require both physiological progesterone and androgen replacement- sometimes to balance excessively high endogenous estrogens, usually to accompany necessary ERT for full balance.

ndb

TESTOSTERONE and ESTROGEN IMPLANTS- IMPLANT CONTRACEPTION.

update 4 March 2013:  the bad news for cheats – especially after cyclist Lance Armstrong’s confessions in January  2013, and the St Valentines Day massacre – the   Blade Runner Oscar Pistorius media frenzy  including unfounded accusations of steroid abuse ‘roid rage – is that testosterone is not recommended and prescribed for bodybuilding or performance enhancement, but solely where medically appropriate.

the good new news is that, while worldwide supplies of testosterone periodically run out,  it and estradiol are    now available once more in South Africa as appropriate 70-year old pellet implants for men and women needng HRT .  But the cost including implanting every 4-6 months remains likely much higher than fortnightly selfinjection or daily cream application.

at the beginning of 2013  authorities  were bemoaning the end of attempts to market depot hormone contraception for men.  But given increasing longevity, and falling male and female fertility, and potentially double the duration of fecundity of men compared to women, and the  real hazards of male and female sterilization and continuous female contraception with all current commercial ie patented synthetics,  for the determined couple  implants offer physiological reversible contaception without the risks of commercial patents.  For males implants of testosterone and progesterone, and for the female  triple implants of testosterone progesterone and estradio,  remain an option to be explored.

Jan 2010:  the important  report  from South African authorities on testosterone replacement for men  is wrong on one account:  such replacement with injection need not cost almost R6000pa  for the  ideal 3monthly German Schering AG ultralongacting brand.

as this column has repeatedly pointed out, physiological depot  injection has been available in South Africa for almost 70 years.  Currently it retails at perhaps R350 per gram as depotestosterone,  the equivalent dose to the 3monthly 1gm  injection (ie 160mg/fortnight)  being 160mg 1.6ml  every 2 weeks ie a cost of about R1400 per year.

This is easily and safely self-injected subcutaneously with a tiny (insulin) 25g needle, and gives physiological blood levels to most men – as with all chronic drugs, the dose and interval  simply needs to be titrated to individual metabolism and response, always under periodic medical screening. Eldrely men usually need and tolerate perhaps 20% less than younger men, who may well tolerate 200mg/fortnight.

It is blatantly wrong  to give the shortacting Sustanon monthly- this brand has been banned by authorities- and  unphysiological to give monthly the gold standard   depotestosterone cypionate / enanthate- with a life of about 3 weeks, since it is well known that the irrationally marketed higher dose for less frequent injection  eg 400mg imi monthly will give the adverse peaks and troughs that Dr Hafferjee notes. It’s like condemning  eg spirits or wine when 4% beer provides far less alcohol- but common sense tells us they are equally good (or bad!),  just the dose and interval needs to be proportionate.

Authoritative data on rational dose and interval of old depotestosterone has been freely available since at least 1991, so there is no justification whatsoever for proclaiming Nebido or other costly  forms of testosterone replacement  as the necessary gold standard- this is classic marketing hype.

We have long insisted that in this age of gender equity, men are as entitled as women to appropriate HRT- but the obtuse authorities and their stupid medical advisors refuse to recognize that both genders equally need all appropriate hormone replacement including physiological sex hormones for their vast life-extending multisystem benefits, least of which is sex.

Yet Discovery Health  has recently refused an elderly man testosterone replacement (recommended by his psychiatrist)  on the grounds that it is an aphrodisiac. Such refusal  of long-validated endocrine replacement (by their medical officers) amounts to medical negligence let alone defamation, fraud  and woeful ignorance.

Nebido and depotestosterone cypionate/enanthate are equally, superbly physiological if used rationally eg subcutaneously, to avoid the unnecessary multiple risks of intramuscular injection.  It can be questioned whether any patient who refuses to be taught his own injection warrants such costly replacement- the same natural selection applies to millions of insulin-dependent diabetics. And replacement of testosterone often relieves type 2 diabetics of the need to use costly and risky  insulin, when appropriate testosterone and metformin reduce all-cause mortality by perhaps half, whereas insulin in type 2 diabetics does not.

Just yesterday this column decried confusing causation with association in the comm0n  but far from majority universal problem of hyperandrogenism in women. There are only two major anabolic hormones that decline seriously with both aging and disease in both men and women, in whom appropriate physiological testosterone and vitamin D3  replacement (with appropriate physiological estrogen for women) is thus often required lifelong from what is potentially middle age to maintain health into vigorous- rather than frail- old age.

UPDATES: HEALTHY LIVING

This  blog is irregularly updated   with the latest detailed pharmacological information on the ingredients of anti-aging preparations, the powder blend compositions, and mail-order/wholesale prices.

These are all detailed  on the page Product Details and Pricelists. but of course all the ingredients, as food supplements, can be ordered individually to US  or UK  or Japanese pharmacopoea standard anywhere from any reliable importer or manufacturer.

The prices listed are not updated weekly, they are a guide; and  dependent from day to day on imported costs which are mostly rising constantly .

For information email sales@healthspanlife.com (or contact 027836299160).

The public, as well as interested distributors/retailers, are invited to contact Healthspan Life!.

SUPPLEMENTS AGAINST DISEASE/ AGING :

SUPPLEMENTS AGAINST DISEASE/ AGING :

Illness & early death are avoidable;

only aging isn’t..

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some ~15 minerals esp CalMag,Zn,Se, Bo,Cr, I, Mn (Iron in kids & young women).

~15 vitamins esp C,D,B, K, bcarotene, E;

~25 of our own manufactured  Biological – FISH OIL; hormones (melatonin, 5HTP;HRT); enzymes, MSM, CoQ10, arginine, carnitine, ribose, cartilage, glycine, glutamine, lipoic/malic acids, flavinoids, cysteine, proline etc; &

AND Dozens of other biologicals-herbs/plants eg garlic; buchu; nettle; ginger,cinnamon, guai, galega, coleus, gymnema, stevia, milk thistle, cat’s claw huperzine A; borrie, aloe, sutherlandia, – both to improve learning & concentration- FISH OMEGA3 – at all ages- and to improve all systems,

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WARNING re HEAVY DAMAGES FOR NEGLIGENT PRESCRIBING: BISPHOSPHONATES – FOSSY DRUGS- FOR OSTEOPOROSIS?

This column last considered bisphosphonates BPN in February. This  reviews some new papers published since.

ADVANCED  CANCER with bone spread:  Recent major (Cochrane)  reviews confirm that BPNs may be  valuable in   advanced prostate and  breast cancer ,  for reducing skeletal events and maybe pain, although they   do not clearly  influence disease progression or patient survival.

OSTEOPOROSIS: It is now almost 5 years since the balloon went up on the unnecessary major risks of BPN for osteoporosis.  So anyone who was prescribed these dangerous drugs since then for osteoporosis, without the rare special  indications, and who develops BNP-related complications  (or osteoporosis-related fractures) has a strong case for heavy damages against the prescriber, the dispensing pharmacy  and regulator eg the State clinic or medical plan who/which advised/ allowed use of the drug for that condition. .

Bisphosphonates were invented over a century ago but developed over the last 40years  for clinical treatment of metabolic bone diseases,  with the first human trials reported about 35 years ago (Heaney 1976). Why have they been exhaustively tested and now routinely used for prevention and treatment of aging osteoporosis, despite their considerable cost especially risks, and lack of global benefit?

Obviously because as patented designer drugs they are profitable to the Disease Industry – despite the fact that their biggest section on Wiki is about their rare but major adverse effects- to quote Wiki :

  • Oral BPN can cause upset stomach, inflammation and erosions of the esophagus,
  • Intravenous BPN can give fever and flu-like symptoms after the first infusion. The  slightly increased risk for electrolyte disturbances is not enough to warrant regular monitoring.
  • BPN have been associated with osteonecrosis of the jaw – the mandible twice as frequently affected as the maxilla- and most cases occurring following high-dose intravenous administration  for cancer patients. Some 60% of cases are preceded by a dental surgical procedure (that involve the bone).
  • severe bone, joint, or musculoskeletal pain has been reported.
  • BPN  use ( zoledronate and alendronate) is  a risk factor for atrial fibrillation in women. The inflammatory response to BPN or fluctuations in calcium blood levels have been suggested as possible mechanisms..
  • Matrix metalloproteinase 2 may be a candidate gene for BPN-associated ONJ since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of BPN.
  • Long-term BPN  use resulting in severe or over suppression of bone turnover especially at the  femur sub-trochanteric region.  Micro-cracks in the bone maybe  unable to heal and eventually unite and propagate, resulting in atypical fractures, which  tend to heal poorly and often require some form of bone stimulation eg bone grafting.

NO COMPELLING INDICATIONS FOR BPN IN OSTEOPOROSIS: the Wiki entries for BPN  and osteoporosis are cleverly written by BPN promoters / marketeers – they fails to justify  why BPNs are “the most popular first-line drug”… and the overwhelming evidence that favours combined natural supplements: eg that in the Womens Health Initiative, appropriate hormone replacement HRT ie started soon after menopause is safe up to 10 years of use, halved fracture rate and colon cancer, and lowered all other chronic major degenerative diseases AND breast cancer AND  premature deaths by a third.  BPNs have risks but no  benefits other than fracture reduction- ie for osteoporosis, no compelling indications  and the legal eagles are hungry.. .

BPN-ASSOCIATED OSTEONECROSIS IN LONG BONES: Guanabens from Spain first described long bone fractures related to BPN in 1994,  and more such cases (iatrogenic Toulouse-Lautrec disease) are reported now from the UK.

ATRIAL FIBRILLATION:   Denmark reports some 30% increase in potentially crippling atrial fibrillation in patients with fractures treated with BPN  – whereas it is common cause that appropriate supplements drastically reduce arrhythmia eg fish oil halves sudden death.

Italy now reports increase in hypocalcemia and raised serum creatinine ie kidney impairment after BPN  for cancer . . Sweden reports no benefit of 2 years’ BPN   on knee prosthesis migration. The incidence of metabolic bone disease and all other system complications in intensive care is notorious – and a   Princeton report gives no justification for BPN use in ICU when all the safe natural supplements are essential and ensure better protection globally..

Canadian study shows that ” managed intervention” after osteoporotic hip fracture prevented  4 new hip fractures and gained 4 quality life-years –   but the available abstract omits what the interventions were, and whether survival was increased.

And while all rational evidence-based appropriate prevention and treatment of osteoporosis – the permanent baker’s dozen of safe natural supplements- reduce all-cause chronic degenerative disease and mortality by at least a third, without any risks, – BPNs  have increasingly recorded risks both short term and long term, with no extraskeletal benefits, despite reducing the fracture risk (spine -Cummings 2002; hip Nguyen 2006) by up to a half.

OSTEONECROSIS OF THE JAW ONJ:   first reported in 2003,   only 26 cases of ONJ  on oral BPN could be found  reported worldwide up to Sept 2006  in a  2007 University Pennsylvania study . Only  15 % were men, and the majority involved the mandible.    Now Israel alone reports another 100 cases of BNP- related jaw osteonecrosis – fossy jaw  – and 16% were on oral BPN. The incidence of OJN is  speculated to be between 5% and 11% in cancer patients treated with BPN.

A world-wide  panel produced the  2008  Canadian Consensus Practice Guidelines for BNP Associated Osteonecrosis of the Jaw, but did not estimate  the incidence of ONJ.   It concludes  that “High-dose intravenous BNP have been identified as a risk factor for ONJ in the oncology patient population. Low-dose BNP use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ”  “BPNs have become a cornerstone in the management of skeletal complications of malignancy as well as osteoporosis and metabolic bone disease, as these agents offer tremendous benefit to those with malignancy or metabolic bone diseaseDue to limited and misleading public information regarding ONJ, many patients have discontinued  BPN treatment, resulting in inadequate care of the underlying skeletal condition.”

But the Canadian Consensus paper fails to clarify in what way BPN offers “tremendous benefit” to those with osteoporosis? The  consensus of the majority of practitioners who do not recommend BPN for osteoporosis is that evidence still shows that appropriate HRT with other standard supplements is  the best prevention and treatment not just of osteoporosis but of all the common major degenerative diseases of aging. (The International Menopause Society). This eternal truth and aim- the wellbeing of seniors- is the imperative, not the wishful thinking of Big Pharma to replace natural supplements with designer magic bullets for each disease.

By far the most comprehensive and objective review is  the American Association of Oral and Maxillofacial Surgeons   Position Paper January 2009 Update on Bisphosphonate-Related Osteonecrosis of the Jaw BRONJ: Indications and benefits of BPN therapy:

Intravenous (IV) BPN are primarily used and effective in treatment and management of cancer-related conditions including hypercalcemia of malignancy, bone metastases such as breast, prostate and lung cancer, and multiple myeloma- for which the clinical efficacy of IV BPN  is well established.

BPN have not been shown to improve cancer-specific survival, but they have had a significant positive effect on the quality of life for patients with advanced cancer involving the skeleton.

Oral BPN: By far the most prevalent and common indication is osteoporosis and  osteopenia. They are also used for a variety of less common conditions such as Paget’s disease of bone, and osteogenesis imperfecta of childhood.

INCIDENCE OF BRONJ: Based on case series, case-controlled and cohort studies, estimates of the cumulative incidence of BRONJ range from 0.8%-12%.

ORAL  BPN BRONJ: Surveillance data from Australia estimated the incidence of BRONJ for patients treated weekly with alendronate as 0.01-0.04%. In a survey study of over 13, 000 Kaiser-Permanente members, the prevalence of BRONJ in patients receiving long-term oral BPN therapy was reported at 0.06% (1:1,700).

Demographic and systemic factors:  In the original Position Paper, age, race, and cancer diagnosis with or without osteoporosis were reported as risk factors for BRONJ. Seven studies report increasing age as consistently associated with BRONJ. Sex was not statistically associated with BRONJ.  Other systemic factors or conditions, i.e., renal dialysis, low hemoglobin, obesity, and diabetes, were variably reported to increase the risk for BRONJ. Malignancy type was not statistically associated with an increased risk for BRONJ.

Genetic factors: Sarasquete et al, demonstrated that genetic perturbations, i.e. single nucleotide polymorphisms (SNPs), in the cytochrome P450-2C gene (CYP2C8) gene were associated with an increased risk for BRONJ among multiple myeloma patients treated with IV BPN.

Preventative factors  The AAOMS Taskforce on BRONJ recommended that patients undergo dental evaluations and receive necessary treatment prior to initiating IV BPN therapy.  In addition, given the long-term biologic activity of IV BPN one may hypothesize that different dosing regimens may be equally effective and decrease the risk for BRONJ.

Using a retrospective cohort study design, Coso et al, evaluated the BRONJ and skeletal-related events  e.g. pathologic fracture in multiple myeloma patients using different dosing schedules for zoledronate. These findings suggest that alternative dosing schedules that reduce IV BPN exposure have comparable outcomes in terms of preventing SREs and a decreased risk of BRONJ.

The effectiveness of hyperbaric oxygen therapy as an adjunct to non-surgical and surgical treatment is under investigation at two institutions where a randomized controlled trial is underway. Preliminary results have shown some improvement in wound healing and long-term pain scores, but its use as the sole treatment modality for BRONJ cannot be supported at this time.

Yet despite the fact that osteoporosis and fractures are closely related to and occur along with the major causes of aging disability and premature death – 20% of osteoporotic hip fracture victims die within a year- BPNs have not been shown to reduce any let alone all the other aging diseases let alone premature deaths. The closest a study came to assess the issue was a Singapore analysis of the  30year old clodronate used for up to 2-3 years after breast cancer  – which drug showed no influence on overall survival.

This failure of global benefit of BPNs – which are  in fact never indicated except rarely eg as palliation in preterminal cancer bone lesions – raises the question of criminal negligence when doctors prescribe and medical schemes and Regulators allow BPN use for osteoporosis. Why are BPNs allowed and prescribed when they have no global benefit but numerous serious risks; and when conventional lowcost natural supplements combined do nothing but global good.   eg essential fish oil, essential vigorous-dose blend of vitamins-minerals-biologicals-herbs, essential appropriate HRT , and essential galega-metformin in the overweight let alone obese each lower all-cause chronic morbidity  and death by a third to a half.

It is no defence that adverse effects are rare when  they are  sometimes deadly, and never worth the risk of these drugs since there is rarely overwhelming need to prescribe such drugs- for which there are safe  natural and far more effective alternatives.

CASE REPORTS: In 2007 we saw a well-built  physically active woman of 61years, whose bone density had fallen some 9% on regular DEXA screening  since menopause despite the usual calcium-vitamin D supplement. In 2008  she  decided to delay HRT because of  strong family history of breast cancer. A year later at followup DEXA  on just fish oil plus a modest dose of the standard HealthSpan For-Bone  supplement blend (calmag zinc boron manganese; proline; and vits B6-9-12 – C- D3 & K2), her DXA BMD has risen 2% (2.5% at the spine, 1.5% at the hip).

A small slim 61year old bookkeeper presented a year ago on just calcium &  vitamin D, her 2007 DEXA spinal density 0.99 having fallen 1% from  2005 ie T -1.6  but her hip down 6.3% from 0.792 to 0.764 ie T-2.  Since then, on the Bone Blend and a little estrogen-progesterone-testosterone cream daily, her spine has stayed constant but her hip BMD has risen 2.4% to 0.783.

A new review from Toulouse France has the last word: “Postmenopausal osteoporosis is a chronic disease which justifies long-term treatment.  Efficacious available modern  fracture-reducing drugs raise the question of the best treatment strategy in postmenopausal women .    In this regard, HRT, which allows a more global approach to the menopause-induced consequences of hormone deficiency than the sole prevention of osteoporosis,  should be privileged… Use of BPN or strontium ranelate should be thus (at best) be reserved for a more advanced age, when the prevention of hip fracture becomes mandatory“. .

Yet, because it is profitable, the fashion grows to treat the elderly with grossly expensive designer oral strontium, or designer injections of BNP or hormone analogues (of calcitonin or parathormone) – despite the fact that these experimental agents have no extra-skeletal benefits (ie improving cardiovascular, muscle, immune, brain function),  have never been tested in longterm studies  for at least 6-10 years to test their safety as has eg HRT in the Nurses’ and WHI studies.

But millions of years of bipedal evolution, and numerous studies over the past century, show that all that is required to  maintain maximum mobility, mind and mood to enjoy life is lifelong supplements as listed above, appropriate to youth, parents, the middle-aged and seniors.. including healthy seniors’ sexuality. It is  too late postponing  prevention  till wished-for healthy advanced age- which most do not reach due to early demise, or irreversible crippledom from largely avoidable fractures, strokes, heart failure, arthritis, or dementia.

The Israelis’ maxillofacial team lament that “Solutions for decreasing morbidity and poor outcome of ONJ remain elusive.” The answer is painfully obvious: avoid iatrogenic ONJ by avoiding  BPN -even orally- except for advanced cancer with bone metastases, but back up lower dose  BPN  with all the  anabolic supplements.

A risk of “only” 7 in 10 000 may reassure a patient being offered BPN for  osteoporosis- but if she decides to sue for damages for prescription of totally unnecessary hazardous therapy, the prescriber doesnt have a leg to stand on when the gold standard is appropriate titrated supplements (including HRT)  without risks since  they reduce all risk by at least one-third.

As  wise Chinese taught 2600 years ago, Society, Authorities, Regulators, health professionals have a sacred obligation to above all else prevent avoidable premature death and crippledom with the freely available and low-cost well-proven natural supplements. These must prevail despite the best efforts of Big Business, Big Pharma and their academic and political lobbyists (Governments, Regulators) worldwide to ignore if not outright suppress safe effective old natural  supplements  (as the FDA and EU are doing) in favour of Diseases and Modern Drugs that Pay – but do not reduce all-cause  disease and mortality .

ndb

TOWARDS MANAGED AGING part 3

The first two chapters have covered musculskeletal, cancer and cardiovascular diseases and HRT.

THE COMMON PATHOPHYSIOLOGIES:  So apart from genetic programming, there are at least six possible pathophysiologies common to the preventable aging co-morbidities of apoptosis (our predestined cell death- only cancer cells are immortal) , fattening-diabetes-cancer; osteoporosis-fractures, and CVD-stroke.

What ranking to give them depends on the individual and tribe.

*catabolism by (relative) gonadopause ie sexhormone deficiency without a balancing fall in catabolic cortisol levels- especially when gonadopause is brought on early by sterilization, hysterectomy, infection, cancer therapy, other chronic disease, or high stress and pollution;

*nitric oxide depletion;

*lifelong and progressive deficiency of the score other human biologicals- especially the marine essential fatty acids (EPA eicosapentanoic acid and DHA docosahexanoic acid- so essential from conception to death for both cell maintenance and immunity;

*increased reactive oxygen species ROS due to falling endogenous and dietary antioxidants;

*common aging-related deficiency of  minerals eg magnesium, calcium, zinc, chromium, lithium, selenium, manganese, boron,  (iron); vitamins; and human biologicals eg chondroglucosamine, CoQ10, carnitine, ribose, arginine, carnosine, Nacetylcysteine (and the sex hormones);

*insulin resistance – prediabetes, metabolic syndrome, PCOS, diabetes; and

*accumulating overload of: multiple metals eg cadmium, iron, aluminium, mercury, lead, arsenic, asbestos, copper (even zinc and iron); radiation; and estrogenics eg pesticides, plastics and sexhormone tablets, and from smoking, food and environmental pollution, that can simultaneously promote cancer, neuro-/vascular and osteoporosis problems.

There is a huge basket of natural supplements- fish oil, cal-mag zinc, boron, lithium, the vitamins A (bcarotene) to K, and the human biologicals (eg proline, CoQ10, arginine, ribose, carnitine and appropriate hormone balance with eg testosterone-estradiol -progesterone, growth hormone), and galega and other herb extract. These are trophic in improving anabolism ie immune protection, tissue regrowth, antioxidation, optimal NO levels, and preventing sugar tissue damage- advanced glycation end products AGES, atheroma and arteriosclerosis as well as collagen and mineral loss from diverse muscle and bone – ie preventing many of the risk factors for both fractures (frailty, weak bones and muscles – skeletal and smooth ie gastrointestinal and heart ) and vascular and immune and malignant disease .

Given the common pathogenic factors of all the common major aging diseases, one should simply add the natural supplements- arginine glutamine and proline, vitamins, minerals, glucosamine-chondroitin, and the other natural insulin sensitizers eg N acetyl cysteine, ribose, carnitine, CoQ10 and galega officinalis, to combat all aging diseases; and when hypogonadism becomes likely- with chronic illness, or from middle age- add appropriate parenteral balanced physiological-dose testosterone-estradiol- progesterone to restore the average levels of healthy slim youthful adults.

Detox: While some of these above supplements may be chelators – removers of heavy metals- in their own right, the high prevalence of metal overload may justify routine addition to supplements (within recognized tolerance and safe limits) of extra harmless non-prescription chelators like, vitamin C, thiamine, magnesium, selenium, zinc, garlic, lipoic acid, malic acid, and bromelain, and the aminoacids eg calcium EDTA, carnitine, cysteine.

CONCLUSION:

with plenty of research to prove it, it is never too early, and never too late, to  do easily what’s necessary to avoid most of the risks for the linked aging diseases that disable and kill prematurely – frailty, obesity-diabetes, circulatory (heart, stroke), arthritic, fracturing, blinding, deafening, dementing and early death.

What’s necessary is simply

*sensible diet and lifestyle including exercise and recreation;

*lifelong appropriate vigorous nutritional supplements including appropriate hormone replacement; and

*avoidance of smoking and overweight, sugar and cooked fats, and if possible avoidance of any modern man-invented drugs (or foodstuffs eg aspartamate, cornstarch) for chronic use including hormone therapy- especially man-designed hormones, and drugs invented to replace natural drugs eg to reduce cholesterol, obesity, fractures, pain, anxiety, depression, hypertension, memory loss etc.

Usually both natural supplements and other complementary therapies, and old proven “drugs” (like metformin for overweight/ infertility/ diabetes, or lowdose reserpine + lowdose co-amilothiazide as baseline therapy for all hypertension) are both safer and better- if not as fast- as modern marketed therapies.

(for detailed scientific links and refs, see the technical version of 13 Sept 2008)

HRT CANCER SCAREMONGERING: BREAST CANCER HAS VERY LOW MORTALITY.

More scaremongering about irrelevant data:

Once again the BBC yesterday published an alarmist report without scientific validity.

But uniquely big size , and cost (~$1 billion for a complex study involving 161 800 postmenopausal women) do not guarantee validity, as Drs Prentice and Anderson stress in their excellent  major 21page  recent overview of the landmark Womens’ Health Initiative WHI.  The source, the latest   WHI report from the notoriously disease-industry- biased New England Journal of Medicine NEJM,  covered an impressive 58000 postmenopausal women, ~300 000 PMW years on HT, up to 30 years of  postmenopausal statistics  on and off megadose oral hormone therapy OHT- not  physiological hormone replacement HRT .

Once again this BBC, and the source NEJM 15page,  report – as is repeated  BBC and NEJM style – in carefully focusing solely on the overblown scare of breast cancer BRCA  when other (preventable with appropriate parenteral HRT)  diseases will kill and disable >15 times more–  omit   cardinal facts, omissions which (apart from crucial statistical errors) immediately discredited the early  WHI  HT  reports from mid-2002 :

1.like the original 2002 WHI  HT report, it fails to give the results by age-group: in both studies the majority of women were well over 60years at screening;

2. it fails to disclose mortality data by all-cause and by common disease and age-group- eg in the estrogen-only arm of the 2004  WHI report, both breast cancer and all-cause major morbidity and mortality was significantly reduced in the women who were under 60yrs at enrollment;

3. it fails to acknowledge that using oral xenohormones OHT especially synthetic medroxyprogesterone MPA has for over 50years consistently been shown to be less safe than estrogen alone and especially than physiological replacement with balanced human parenteral estrogen, progesterone and testosterone. We and others  stopped using  potent  xeno-OHT (equine estrogen, synthetic progestin)  in the early 1990s because both the literature since the 1950s, and our experience, and longterm preventative endocrinological (not symptom-relief-based) practice, overwhelmingly argued against anything but physiological replacement of human hormones;

4. the 2004 estrogen-only arm  report of WHI confirmed previous studies and experience that use of even oral estrogen OHT appropriately in healthy young women for up to 10 years reduces all-cause major disease and breast cancer morbidity and mortality; it is almost 30 years since Brian Henderson ea (1980 onwards) showed that the incidence of breast cancer rises steadily after >12years of OHT with equine CEE;

5. oral synthetic progestins especially MPA are a major breast  cancer (and cardiovascular, and osteoporosis)  risk factors, with Horwitz ea in New York  recently confirming that it is progestin, not estrogen, that initiates growth in otherwise dormant breast cancer cells; and

6. There never was evidence from either observational studies, practice or eg the US Nurses’ Health Study, or the Heart and Estrogen Study HERS or PEPI, to justify the bizarre WHI protocol to inappropriately randomize women well over 60years, the majority HT-naive and overweight (BMI>25kg/sqm),   with predictable latent if not obvious hypertension-vascular disease, to start the  OHT with two  already long-discredited xenohormones. This was borne out by the small Oulu 2006 randomized controlled trial (Heikinnen ea) which confirmed that European OHT (lower-dose oral human estradiol plus more modern safer progestin than MPA), in younger fit PMW abolished any serious adverse disease events let alone deaths for a mean of 10years.

7. The dietary arm of the WHI showed the miniscule mortality rate of breast cancer today:    the women who got breast cancer under observation (0.45% per year) had a deathrate from breast cancer of only 0.02% per year ie (unlike the death rate from all other cancers), fewer than 1 in 20 of breast cancer sufferers die each year  of the breast cancer. This 0.45% breast cancer incidence (which rarely  cripples those who survive)  contrasts with the 2/3 lower   hip fracture rate off HT of 0.15% per year- which kills 20% of victims, and cripples three-quarters of the survivors- whereas appropriate early  and permanent balanced HRT (testosterone and estrogen) combined with the basket of a dozen natural  vitamin-mineral supplements virtually abolishes osteoporotic  hip fracture.  In  western women, by contrast with the average <4% of  annual deaths  that are from breast cancer,  over 50% of postmenopausal deaths are from vascular diseases – which like osteoporotic fractures and breast cancer are largely preventable with natural supplements.

8. and even appropriate OHT may reduce the mortality from breast cancer and all causes  by a third:

a Medline review up to 2002 of OHT after breast cancer showed no  adverse effect on recurrence and mortality;

a study from Australia in a cohort of 4022 postmenopausal women diagnosed with breast cancer between 1993 and 2000 showed 36% lower breast cancer  mortality and 31% lower all-cause mortlaity in HRT ever-users;

and a 2008 study of PMW with BRCA  shows “Tumor prognostic factors were better and survival rates higher for both CEE and combination HT users of any duration. Use greater than 10 years correlated with node-negative disease, mammographically detected tumors, and 100% survival. CEE supported minimal proliferation; MPA induced cell death; CEE+MPA results were similar to E alone. CONCLUSIONS: HT users, regardless of type or duration of HRT use, continued to have higher survival rates. In vitro results supported the clinical finding that outcomes for users of E and E+MPA were similar. ”

Funded research studies, and risky HT, and for-profit incentives,  are potent stimuli  to mass screening interventions. The very low rate of breast cancer deaths after breast cancer is arguably due to the gross and (in those without risk factors eg family history, obesity)  unwarranted over-diagnosis of silent breast  cancer by screening mammography of the well, who (like asymptomatic men with silent prostate cancer) would often have died old of other causes without the cancer ever causing symptoms. This was clearly shown in the recent Canadian mammography screening trials.

These crucial facts have been endlessly presented at the world authority congresses of eg the International IMS and British BMS Menopause Societies since 2002, so much so that even leading Americans (as in this new NEJM paper) have finally stopped calling unphysiological oral hormone therapy (OHT-which uses doses effectively 10 to 100 times stronger) physiological human sex steroid replacement- SHRT.  Medical HRT obviously in simple English encompasses all hormone replacement, so SHRT distinguishes sex or steroid HRT from the dozen other HRT acronyms.

The crucial differences between (risky) OHT and appropriate safe physiological parenteral SHRT have yet again been summed up in a new paper from the IMS (Genazzani ea 2008). All these issues and references have been posted on the IMS and BMS websites, and analyzed the past year in this column. But the American Disease Industry – led by Big Pharma like Wyeth, and it’s front the (USA) FDA and the (European) EMA, does not give up in it’s profit-dominated campaign against the proven effective old and natural supplements  (eg appropriate human hormones) – it’s War Against Patients, it’s cancer scaremongering; why should it give up, since only disease pays! Prevention Does Not pay!