(No emergencies or surgery- these must go to nearest polyclinic or hospital ER). .
or consultations by Telephone/email where appropriate.
Accompanying his 32year old partner (with like her mother BRCA+ breast cancer ), a young man this week complains sorrowfully of total erectile failure within three days every time he resumes fluoxetine for longstanding depression.
This may suit those patients who eschew sexuality, who knowingly choose chemical castration.. But the drug doesnt fix the causes of depression, merely palliates, often no better than a placebo, sometimes worse- compared to natural multibeneficial antidepressant supplements.
We already long live in a sea of estrogenic endocrine disruptors decimating many species including humans, like pesticides and PCBs, as so aptly described by Deborah Cadbury and Prof Nils Skakkebaek in classic books eg The Feminization of Nature and The Estrogen Effect.
The commonest prescription drugs (synthetics- antidepressants; major psychotropes; amoxicillin, oxidants ( betablockers eg atenolol; nonsteroidal anti-inflammatory NSAID (which block antidepressant effects –the Paul Greengard hypothesis 2011 Rocherfeller Inst NY); statins (cholesterol -steroid and insulin disruptors), and patent synthetic sex hormones- are now routine if not mandatory prescription worldwide due to ruthless relentless marketing pressure- disease-mongering for profit- even in children, and worse, in patients with cancers. The commonest cancers- breast, prostate, uterus- are estrogen-driven.
Such environmentally and biologically hostile designer patent drugs-for-profit are increasingly detectable in surface wastewater globally from human excretion, and thus drinking water supplies .
Endocrine disruption studies of antidepressants (eg fluoxetine Prozacs, mianserin Lantanon (its commercial analogue successor is now Remeron), Bupropion Wellbutrin Zyban; Venlafaxine Effexor and desimipramine) in surface water in Canada, USA, Mexico, Brazil and Belgium since 2006, and longer for antipsychotics, statins and NSAIDS, show estrogenic ie antiandrogenic risks for eg gender development and thus for breast/prostate cancer, for virility and fertility..
Doctors mostly blithely ignore that reproductive young females have by evolutionary reproductive necessity 100fold lower androgenic:estrogenic balance (eg 3:1) than men (eg 300:1), and are also far more prone than males both to estrogenic contraception prescription harm, and to common major depression and autoimmune disease like rheumatod arthritis and lupus, and thus to the double peril of mutiple estrogenic prescription.
Recently common NSAIDs eg ibrufen, diclofenac and mefanemic acid have been shown to be estrogenic in fish.
But such elective prescription of ( endocrine disruption) cancer- and infertility- promotors (antidepressants, NSAIDS, hormone contraception and HRT etc) , is hardly desirable or ethical at any age, especially when patients and their parents are not informed of the grave risks of these drugs with no proven longterm benefits (except for contraception).
new reviews gives more insight from a plastic surgeon into prevention, including the harms of xray mammography.
and into the gross dangerous overprescription of diabetogenic depressing hepato-nephro-myotoxic statins for all.
Popular painkillers eg opioids like oxycodin, fentanyl, tramadol on the other hand are similarly also powerful longacting hypoandrogenism–inducing drugs promoting estrogen dominance – which further complicates the misery and depression of those in chronic pain or depression, including from cancer, especially in women as well as men; who thus require monitoring of gonadal hormone levels and, if deficient, testosterone replacement. Aloisi ea Univ Siena 2012.
Aquat Toxicol. 2010 ;100:354-64 .Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus.nMennigen JA, Lado WE, Zamora JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL University of Ottawa, Ontario, Canada. Fluoxetine (FLX) is a pharmaceutical acting as a selective serotonin reuptake inhibitor and is used to treat depression in humans. Fluoxetine and the major active metabolite norfluoxetine (NFLX) are released to aquatic systems via sewage-treatment effluents. They have been found to bioconcentrate in wild fish, raising concerns over potential endocrine disrupting effects. The objective of this study was to determine effects of waterborne FLX, including environmental concentrations, on the reproductive axis in sexually mature male goldfish. We initially cloned the goldfish serotonin transporter to investigate tissue and temporal expression of the serotonin transporter, the FLX target, in order to determine target tissues and sensitive exposure windows. Sexually mature male goldfish, which showed the highest levels of serotonin transporter expression in the neuroendocrine brain, were exposed to FLX at 0.54μg/L and 54μg/L in a 14-d exposure before receiving vehicle or sex pheromone stimulus consisting of either 4.3nM 17,20β-dihydroxy-4-pregnene-3-one (17,20P) or 3nM prostaglandin F₂(α) (PGF₂(α)). Reproductive endpoints assessed included gonadosomatic index, milt volume, and blood levels of the sex steroids testosterone and estradiol. Neuroendocrine function was investigated by measuring blood levels of luteinizing hormone, growth hormone, pituitary gene expression of luteinizing hormone, growth hormone and follicle-stimulating hormone and neuroendocrine brain expression of isotocin and vasotocin. To investigate changes at the gonadal level of the reproductive axis, testicular gene expression of the gonadotropin receptors, both the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were measured as well as expression of the growth hormone receptor. To investigate potential impacts on spermatogenesis, testicular gene expression of the spermatogenesis marker vasa was measured and histological samples of testis were analyzed qualitatively. Estrogen indices were measured by expression and activity analysis of gonadal aromatase, as well as liver expression analysis of the estrogenic marker, esr1. After 14d, basal milt volume significantly decreased at 54μg/L FLX while pheromone-stimulated milt volume decreased at 0.54μg/L and 54μg/L FLX. Fluoxetine (54μg/L) inhibited both basal and pheromone-stimulated testosterone levels. Significant concentration-dependent reductions in follicle-stimulating hormone and isotocin expression were observed with FLX in the 17,20P- and PGF₂(α)-stimulated groups, respectively. Estradiol levels and expression of esr1 concentration-dependently increased with FLX. This study demonstrates that FLX disrupts reproductive physiology of male fish at environmentally relevant concentrations, and potential mechanisms are discussed.
Chemosphere. 2006:;65:1836-45.. Effects of the antidepressant mianserin in zebrafish: molecular markers of endocrine disruption.van der Ven K, Keil D, Moens LN, Hummelen PV, van Remortel P, Maras M, De Coen W. University of Antwerp, Belgium. Due to their environmental occurrence and intrinsic biological activity, human pharmaceuticals have received increasing attention from environmental and health agencies. Of particular, ecotoxicological concern are drugs that affect nervous- and endocrine-systems. Zebrafish genome-wide oligo arrays are used to collect mechanistic information on mianserin-induced changes in gene expression in zebrafish. Gene expression analysis in brain and gonad tissue clearly demonstrated the estrogenic activity of mianserin and its potency to disrupt normal endocrine (estrogenic) signaling, based on induction of molecular biomarkers of estrogenicity (e.g., vitellogenin1 and zona pellucida proteins). The possible mechanism underlying this estrogenic activity of mianserin is disturbance of the Hypothalamo-Pituitary-Gonadal (HPG) axis by direct interference of mianserin with the serotonergic and adrenergic systems in the brain of zebrafish. Taking into account the importance of the HPG-axis, and considering the concept of ‘critical window of exposure’, our results reveal the importance for more elaborate testing of endocrine disruptive effects of aquatic antidepressants at different lifestages and during longer exposure periods (e.g., life cycle studies). Although there is a low concordance between the gene expression results in this study and previous cDNA microarray hybridizations, the global mechanistic expression patterns are similar in both platforms. This argues in favor of pathway-driven analysis of gene expression results compared to gene-per-gene analysis.
University of Algarve, Portugal .buprofen (IBU) is one of the most sold over-the-counter non-steroidal anti-inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels’ gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels’ reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short-term reactive oxygen species (ROS)-generator.
BMC Med. 2013; 11:57.. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. CUNY School of Public Health York, .Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone. METHODS:A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using ‘(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)’ restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.RESULTS:Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13). CONCLUSIONS: Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
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.
update 2 Oct 2010: a practitioner asks what to do for a white female 58years:
1998 ductal cell. lumpectomy, radiation, 15 nodes removed. Tamoxifen 5 yrs.
2009 lobular cell. double mastectomy, nodes removed. Aromasin for next 5 yrs.
Osteopenia -2.3 found inside 1 yr . on Boniva ibandronate 4 yrs, stopped recently. Doesn’t want to take IV drug for osteoporosis. 24 hr urine calcium normal. High vitamin d levels.
takes a lot of calcium, vit d, vit c, vit b complex sups. Takes Prilosec omeprazole for reflux and hiatal hernia. chronic insomnia. The questioner does not reveal her bodymass index or resting morning cortisol level or insulin resistance- all of which may well be raised; nor give her crucial vitamin D and C intake or vitamin D blood level. It is a question of evidence, not opinion – dogma- or laboratory average population ranges , as to what are optimal intakes and blood levels.
This column has regularly reviewed the conflicting views and evidence on osteoporosis; BNP and breast cancer; and the safe multisystemic efficacy of using the score of natural supplements- including appropriate combined hormone replacement therapy – that safely oppose both osteoporosis – bone and muscle frailty- and the associated chronic major involutionary diseases of aging especially vascular disease, dementia and cancer. .
The antireflux proton pump inhibitors PPI drugs notoriously aggravate osteoporosis; and for average reflux are not necessary with use of slippery elm, apple cider vinegar, simple calmag and sensible diet and lifestyle. It has been known for years that PPIs more than double risk of osteoporosis, so why take them?.
On the other hand, the pluripotential hormones of darkness and light – vitamin D3 and Melatonin – combined with the other mulibeneficial natural supplements that synergistically relieve/ reduce insomnia, reflux pain, cancer, depression, memory loss and all other significant major chronic degenerative diseases of aging.
As this column regularly updates, Metformin too is a natural supplement (plant) co-hormone- a veritable panacea- that reduces all major chronic disease and mortality by about a third- including cancer; and dementia perhaps via reducing serum amyloid levels.let alone tissue oxidation, glycation, vasculopathy. BPN has none of these extraosseous benefits, only deadly risks.
So middleaged patients are at terrible risk of anxiety depression hypercortisolemia, frailty fractures, vascular disease , cancer and dementia after cancer, especially with sex hormone suppression or blockade. They do not need the myriad risky designer drugs touted for prevention of more cancer etc, all they need urgently and permanently is the scores of appropriate natural balanced supplements as this column regularly reviews- most of which supplements can simply be mixed in a tub of customized powder blend to be drunk twice daily. .
:Feb 13, 2009 In response to Death-knell-for-bisphosphonates-for-osteoporosis-breast-cancer-time-for-class-action-against-bisphosphonate-damage last week, a world-renown emeritus professor of radio-oncology comments:
“the action of the bisphosponates BPN is to inhibit osteoclastic action and thus reduces bone resorption; the patients tell the story- they get immediate and sustained relief from bone pain; if they are on opiates the need is much reduced. Of course palliative RT is valuable, but often if pain recurs after RT the BPN give welcome relief, at least in my experience.
The IV BPNs are also very useful in the oft-times encountered hypercalcemia often threatening myeloma- and other cancer patients. I am not however, too conversant with D3 in this setting!” But the first reference links are the latest in the clinical field of BPN and cancer.
Other than in terminal cancer cases- when it doesn’t matter what convenient pain relief is used- the problem with bone pain in cancer always is, what is the cause? either bone resorption from the catabolic effect of cancer (via eg high parathyroid hormone PTH); OR cancer eating away at bone itself, OR something else common OP unrelated to the cancer.?
But FOR CANCER-RELATED bone pain lesions – whether directly from cancer there, or from remote metabolic effect – where are the trials comparing BPN with other antiresorptive antineoplastic ANTIINFLAMMATORY ANALGESIC ANABOLICS ie testosterone (or occasionally estrogen/ other antiandrogen) and vitamin D3?
Obviously bone metastases are attacked with appropriate chemo-/ xray XRT, cortisone, testosterone AND if deficient, vitamin D3.
To put it the other way round: where is the evidence that BPN – at cumulative cost and risk- adds benefit to the multiple attack? where the evidence that- unlike testosterone and vitamin D3- BPN has any benefit except on bone pain? Hypotheses based on in vitro and animal and human cell culture studies have not translated into even good observational comparative evidence favouring BPN as good benefit:cost ratio for osteoporosis or cancer.
The oncologist answers in the traditional mode, by experience that BPN works. But evidence-based medicine EBM asks where is the comparative evidence for BPN to challenge the evidence that we have better multi-attack without BPN – when these supplements are not equally commercially promoted and tested in controlled trials for the usual commercial reason ?
The dream of drug manufacturers is eternal, that their raincheque designer drug- statin or BPN or antihypertensive- will prove to be a safe multisystem panacea as is metformin and many other supplements like vitamin D3 or testosterone. But after more than 30 years of BPN and statins, no trial in humans has yet shown this for BPN or statin or any other original designer drug.