Tag Archives: androgen

MODERN SYNTHETIC PALLIATIVES- ANTIDEPRESSANTS,ANTIPSYCHOTICS, ANALGESICS, STATINS AND ANTI-INFLAMMATORIES – ARE RISKY NON-CURATIVE ESTROGENIC /FERTILITY ie METABOLIC ENDOCRINE DISRUPTORS

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.

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Reprod Toxicol. 2012:34:80-5. In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.Müller JC, Imazaki PH, Boareto AC, Lourenço EL, Golin M, Vechi MF, Lombardi NF, Minatovicz BC, Scippo ML, Martino-Andrade AJ, Dalsenter PR.  University of Paraná,  Brazil.     .Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer.    Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
Pharmacol Biochem Behav. 2013103: 659-65..Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Lemini C, Cruz-López B, Martínez-Mota L  Universidad Nacional Autónoma de México, Mexico.Estrogen therapy may produce antidepressant-like actions, but the side effects, such as thromboembolic events, may restrict its use among women. The 17β-aminoestrogens (AEs) [prolame [17β-(3-hidroxy-1-propylamino)-1,3,5(10)-estratrien-3-ol)], butolame [17β-(3-hidroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol)], and pentolame [17β-(5-hidroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol)] induce estrogenic and anticoagulant actions, effects that could prove advantageous in an estrogen therapy; however, their antidepressant-like effects have not been described. The objective of this study was to determine the effect of these 17β-AEs (prolame, butolame and pentolame) in the forced swimming test (FST), an animal model sensitive to antidepressant drugs, and to establish the role of estrogen receptors in such actions. Ovariectomized female rats treated with prolame (10-200 μg/rat) showed a reduction in immobility and an increase in active behaviors in the FST, while this effect was not produced by butolame and pentolame (10-200 μg/rat). The antidepressant-like effect of prolame was similar to that of 17β-estradiol (E2, 5-20 μg/rat), sharing with it a biphasic profile but at higher doses. Antidepressant-like actions of prolame and E2 were not associated with changes in locomotor activity. With respect to a control group tamoxifen (15 mg/kg) by itself produced no changes in all behavioral evaluations, but canceled the antidepressant-like effect of prolame and E2. It is concluded that estrogen receptors participate in antidepressant-like effect of both estrogens in the FST. Antidepressant-like activity of different AEs is discussed considering their differences in chemical structure and the schedule used. Our results show additional central actions of prolame besides its pro-sexual, anti-coagulant, estrogenic and anxiolytic activity.
Aquat Toxicol. 2011:104::38-47. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Schultz MM, Painter MM, Bartell SE, Logue A, Furlong ET, Werner SL, Schoenfuss HL  The College of Wooster, OH   USA   Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish–a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

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.

Pharmacol Biochem Behav. 2008 ;88:332-40.Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats.Martínez-Mota L, Cruz-Martínez JJ, Márquez-Baltazar S, Fernández-Guasti A  Instituto Nacional de Psiquiatría  Mexico City In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17beta-estradiol (E2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E2 (5, 10, 20 and 40 microg/rat) or the combination of E2 [at sub-threshold (5 microg/rat) and optimal (10 microg/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E2 at the supra-physiological doses of 10 and 20 microg/rat produced antidepressant-like effects. E2 at 5 microg/rat (that re-established the levels of this hormone to physiological levels) and at 10 microg/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST.

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.

 

J Hazard Mater. 2013 Jun 15;254-255:242-51. .Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish.  Ji K, Liu X, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Seoul National University,  Korea.This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

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.

 

Aquat Toxicol. 2011 ;105:264-9..Non-steroidal anti-inflammatory drug (NSAID) ibuprofen distresses antioxidant defense system in mussel Mytilus galloprovincialis gills.Gonzalez-Rey M, Bebianno M   University of Algarve,  Portugal.Active pharmaceutical ingredients (APIs) are presently considered an emergent class of environmental contaminants. Ibuprofen (IBU) is one of the most applied non-steroidal anti-inflammatory drugs (NSAIDs) in the world. Several authors report the occurrence of IBU in influents and effluents of waste water treatment plants (WWTPs), surface, river and public tap water in numerous countries. However, very little is known about the risks and chronic effects of IBU exposure in non-target organisms. This approach undertakes the assessment of several oxidative stress biomarkers responses through the analysis of antioxidant enzymes activities (superoxide dismutase – SOD, catalase – CAT, glutathione S-transferase – GST, glutathione reductase – GR) and lipid peroxidation (LPO) levels in sentinel species mussel Mytilus galloprovincialis gills exposed for 2 weeks to an environmental realistic concentration of IBU. Results clearly show the significant induction and positive correlation between SOD activity and LPO in exposed gills, concomitant to an antioxidant defense depletion of CAT, GR and GST compared to controls. The integration of all biomarkers in mussels’ gills separates non- and exposed groups supporting the breakdown of the redox defense system and IBU’s pro-oxidant action. Further studies are needed to test possible endocrine disruption effects in mussels’ reproduction fitness as IBU is involved on prostaglandins biosynthesis inhibition.

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.

 

Chemosphere. 2009 ;77 :1285-91.Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in Canadian sewage and surface water samples.  Lee HB, Peart TE, Svoboda ML, Backus S. Aquatic Ecosystem Protection Research Branch, Environment Canada      Rosuvastatin (RST) and atorvastatin (ATO) are prescription drugs and members in the statin family used for the treatment of elevated cholesterol levels. A method using solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of ATO, RST and its metabolite rosuvastatin lactone (RSTL) in sewage and surface water samples has been developed. In the influent and effluent samples collected from 11 sewage treatment plants located in Ontario, Canada, ATO, RST, and RSTL were detected in all samples with median concentrations of 166 ng L(-1) (influent) and 77 ng L(-1) (effluent) for ATO, 448 ng L(-1) (influent) and 324 ng L(-1) (effluent) for RST, as well as 158 ng L(-1) (influent) and 41 ng L(-1) (effluent) for RSTL. Due to the inter-conversion between RST and RSTL, the total concentration of RST and RSTL in a sewage sample should be reported. The median removal rate by wastewater treatment was 66% for ATO and 22% for RST and RSTL combined. These statins were quite persistent in sewage. After a storage period of 21 and 62 days, there was only a slight decrease in ATO concentration and no change in the total RST concentrations. These three compounds were also detected in a number of surface water samples at low ng L(-1) concentrations. This is the first reported occurrence and fate of RST and RSTL in the Canadian aquatic environment.
Ecotoxicol Environ Saf. 2011;74:1216-25. Chronic exposure to diclofenac on two freshwater cladocerans and Japanese medaka.Lee J, Ji K, Lim Kho Y, Kim P, Choi  Seoul National University,  Korea.
Consequences of long-term exposure to diclofenac up to 3 months were evaluated using freshwater crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). Marked decrease of reproduction was observed at 25 mg/L for D. magna, and at 50 mg/L for M. macrocopa. Three-month exposure of fish to 0.001-10 mg/L of diclofenac resulted in significant decreasing trend in hatching success and delay in hatch. The hatching of the eggs produced from the fish exposed to 10 mg/L was completely interfered, while fertility of the parent generation was not affected. Gonadosomatic index (GSI) of female fish was also affected at 10 mg/L. Predicted no effect concentration of diclofenac was estimated at 0.1 mg/L, which is a few orders of magnitude greater than those observed in ambient water. Therefore direct impact of diclofenac exposure is not expected. However its bioaccumulation potential through food web should warrant further evaluation.\
J Toxicol Environ Health A. 2009;72(10):633-41. Life-cycle exposure of fathead minnows to a mixture of six common pharmaceuticals and triclosan.Parrott JL, Bennie DT Water Science and Technology Directorate, Environment Canada,Fathead minnows were exposed for a life cycle to environmentally relevant concentrations of a mixture of six common pharmaceuticals and one personal care product (nominal concentrations: 1,000, 300, 100, 30, or 10 ng/L). Mean measured concentrations of each chemical in the highest fish exposure aquaria were: naproxen 793 ng/L, gemfibrozil 662 ng/L, diclofenac 331 ng/L, ibuprophen 217 ng/L, triclosan 115 ng/L, salicylic acid 67 ng/L, and acetaminophen (chemical analysis inconclusive, nominal 1000 ng/L). Fish exposed for a life cycle even to the highest concentrations of the six pharmaceuticals and personal care product (PPCP) mixture showed no significant changes in growth and development compared to control. Length, weights, condition factors, liver weights, and gonad weights of PPCP-exposed fish were similar to water and solvent controls (0.000005% ethanol v/v). There were no marked effects of PPCP mixture exposure on external sex characteristics of the fish or on egg production. The only parameter that appeared to be affected was percent larval deformities in F1, which showed a significant increase in the 100- and 300-ng/L (nominal) PPCP mixture. Larvae from control fish had 4.7% (water controls) and 3.4% (solvent controls) deformities, compared to 9.3% in the 100-ng/L (nominal) PPCP mixture and 9.2% deformities in the 300-ng/L (nominal) PPCP mixture. Chronic exposure to environmentally relevant concentrations of seven PPCP most often detected in Canadian municipal wastewater effluents (MWWE) did not appear to affect fathead minnow survival, growth, or egg production, although it produced quantitative increases in deformities in the F1 generation.
Hum Reprod. 1993 Aug;8(8):1168-72.Autonomic nervous modulation and effects of a prostaglandin synthase inhibitor on human cervical secretion.Jonsson B, Hammarström  Karolinska Hospital, Stockholm, Sweden.Modulation of cervical secretion at ovulation time was studied in 10 women with regular menstruations. In an in-vivo model with repeated collection of mucus samples during three 90-min periods, the amounts of mucus in a control cycle and in three experimental cycles were compared. Drugs interacting with the autonomic nervous system and a prostaglandin synthase inhibitor were administered at time of ovulation. The cholinomimetic drug carbacholine significantly increased cervical secretion, while the anticholinergic drug butylscopolamine markedly inhibited this secretion. A long-lasting decrease in secretion was seen after administration of the prostaglandin synthase inhibitor diclofenac. Beside regulation of cervical secretion by the ovarian hormones, these results suggest an autonomic nervous modulation of cervical secretion, and in addition an impact on cervical by a prostaglandin synthase inhibitor. The effects on fertility regulation in the female are discussed.
Water Res. 2010 Jan;44(2):555-66.   Oxidative transformation of micropollutants during municipal wastewater treatment: comparison of kinetic aspects of selective (chlorine, chlorine dioxide, ferrate VI, and ozone) and non-selective oxidants (hydroxyl radical).Lee Y, von Gunten U. Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland.  Chemical oxidation processes have been widely applied to water treatment and may serve as a tool to minimize the release of micropollutants (e.g. pharmaceuticals and endocrine disruptors) from municipal wastewater effluents into the aquatic environment. The potential of several oxidants for the transformation of selected micropollutants such as atenolol, carbamazepine, 17 alpha-ethinylestradiol (EE2), ibuprofen, and sulfamethoxazole was assessed and compared. The oxidants include chlorine, chlorine dioxide, ferrate(VI), and ozone as selective oxidants versus hydroxyl radicals as non-selective oxidant. Second-order rate constants (k) for the reaction of each oxidant show that the selective oxidants react only with some electron-rich organic moieties (ERMs), such as phenols, anilines, olefins, and deprotonated-amines. In contrast, hydroxyl radicals show a nearly diffusion-controlled reactivity with almost all organic moieties (k>or=10(9)M(-1) s(-1)). Due to a competition for oxidants between a target micropollutant and wastewater matrix (i.e. effluent organic matter, EfOM), a higher reaction rate with a target micropollutant does not necessarily translate into more efficient transformation. For example, transformation efficiencies of EE2, a phenolic micropollutant, in a selected wastewater effluent at pH 8 varied only within a factor of 7 among the selective oxidants, even though the corresponding k for the reaction of each selective oxidant with EE2 varied over four orders of magnitude. In addition, for the selective oxidants, the competition disappears rapidly after the ERMs present in EfOM are consumed. In contrast, for hydroxyl radicals, the competition remains practically the same during the entire oxidation. Therefore, for a given oxidant dose, the selective oxidants were more efficient than hydroxyl radicals for transforming ERMs-containing micropollutants, while hydroxyl radicals are capable of transforming micropollutants even without ERMs. Besides EfOM, ammonia, nitrite, and bromide were found to affect the micropollutant transformation efficiency during chlorine or ozone treatment.
Toxicol Appl Pharmacol. 2007 Dec 1;225:142-53. .Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, Hecker M, Murphy MB, Yu RM, Lam PK, Wu RS, Giesy JP.Michigan State University,       The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11beta2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11beta2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The beta-agonist salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

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.

TOURISM HEALTH: SAFARI HEALTHSPANLIFE HEALING CAPE TOWN HOLIDAY 2013.

Health- slante, l’chaim!, hayah, sawubona! – in any country or language  is a blessing, a gift- not a right. It is insurance that has to be planned and enforced. Leaving it to fate, illness and hoping for a cure is often too late, sometimes crippling if not often  fatal. With comprehensive natural supplements, we can and should all die peacefully at an  active fit advanced  age  90years +  –   not old, incapacitated and demented. We owe this prevention to both ourselves, our  kids and our aging seniors.

So sensible lifestyle aside, promoting health  includes simple low-cost  (no-xray/no-laboratory) periodic screening:  for all,  from childhood:  of weight,  girth, eyes, teeth, bloodpressure, brainfunction- memory; and ultrasound bones – at any pharmacy/ optometrist, school or clinic;                         and  for women:  checking the breasts and pelvis for risk of  cancer.

The HealthSpanLife  South African Natural Medicine Clinic SANMC next to Cavendish Mall on the slopes of Table Mountain in beautiful Cape Town – one of the favourite world tourist  and heritage centres-  is a specialist clinic  staffed by experienced  registered professional practitioners- a medical internist specialist  (also UK registered);  a homeopath;  and a Muslim nursing sister.

It provides  one-stop holistic screening and diagnostics, and – uniquely-  evidence-based  natural remedies- nutritional support for all symptoms and chronic conditions-  also  for menopause-andropause-genitourinary- breast-sexual dysfunction- obesity-pain/headache –chiropractic  and detox ,

as well as if needed  appropriate modern specialized  testing and prescription medicines for all chronic major conditions including bio-identical hormone replacement for both genders (including implants);

and integrated referrals nearby (and in Gauteng)  as patients desire eg for autism, acupuncture, aromatherapy, physiotherapy, aquarobics,  advanced scopes, delicate restorative micro (eg hands, toes)-as well as major (eg bariatric, spinal,eye-, ear- neuro-)  surgery, infertility, xray/other scans, cancer, hyperbaric oxygen, spiritual intervention, psychiatric-hypno- therapy, and eg genetic profiling and counselling,   dialysis and transplantation, and stem cell therapy. …

Gentle Non-xray  ultrasound bone-density measurement (recommended by Cape Town , UK, and USA universities),  and tactile mechanical breast mapping (recommended by CANSA, UK, USA, Indian and Chinese studies) are available at SANMC (and in Gauteng) by appointment, and are covered by some medical aid plans;  whereas menopause consultations are covered by all open plans.

As typified by a new review last month,    World opinion is to use xray  mammography and  xray bone density imaging  only as last resort and only  in the elderly – or in staging those with breast cancer- because of the major problems and risks of xray imaging..   As world experts Profs Cornelia Baines epidemiologist in Canada, Mike Baum breast surgeon  in London and Peter Gotzsche epidemiologist  in Denmark  say,  there never has been any independent scientific evidence to support hazardous routine mass mammography crush xray screening of well women, let alone any repeated mass xray screening for decades, or the dangerous fictitious marketing hype of the American radiology-Breast Surgeons and Curves International nonsense  that xray mammo screening saves lives ..

While health tariffs must rise with inflation,  where med aid doesn’t cover, New Year 15% discount applies through January on cash-paid clinic services and in-house products. . .

For out-of-town/ overseas  visitors, accommodation and travel locally and throughout Africa and beyond can be arranged by outside experts around  clinic appointments. .  http://www.capetown.gov.za/en/visiting/Pages/default.aspx

For appointments visit  the SANMC at 1st floor no.  15 Grove Medical Bldg on Pearce St  cnr Grove Ave (parking opposite at ABSA on Grove);    or  phone +2721-6831465/  -6717415; or fax  +27865657215; or email the manageress, doctors or Sister at   sales@healthspanlife.co.za  to discuss needs,  timing and preliminary costing. For details, references  and rationale for screening and prevention,  see https://healthspanlife.wordpress.com/?s=screening.

CHRONIC ILLNESS- MANAGED ANTIAGING & GENERAL PRACTICE CLINIC SOUTH AFRICA

update 6 April 2015

In Claremont  Cape Town

A  Specialist Family Internist Clinic offers consultations by appointment especially for managing (and ideally preventing)  the major chronic degenerative diseases of aging  and  maintaining physical, mental (and why not sexual?) vigour to a ripe and healthy old age; as well as preventing and managing acute disease at all ages.

The clinic (a specialist physician and a nutritionalist)  offers all-system evaluation and if available, natural  (as well as essential prescription orthrodox) prevention/treatment including metabolic – weight-endocrine-diabetes; heart-lung -kidney; hypertension; neurological-pain; joint & muscle; abdominal, immune system ie infection, cancer and auto-immune  support;  genito-urinary, & sexual problems;

and appropriate screening – ECG, non-xray ( no-touch thermography- eg thermomammogram;   SureTouch tactile) mammograms, non-xray (ie  ultrasound) BMD ie  bone fracture risk measurement, body composition, and appropriate hormone profiling/replacement.

Phone during office hours for appointment: for Claremont office  ph 021-6717415  or 6831465 (or 083-6299160) – at Grove Medical Bldg 1st floor no 15 (opp ABSA Bank Parkade c/o Grove Ave Pearce Rd)  , or neil.burman@gmail.com ;  or consultation by telephone/Skype or email .

by appointment only:        OFFICE HOURSby appt: ph office:  9am-5pm weekdays, 9am-1pm Saturdays.  AFTER  HOURS up to 9pm any day generally at office: –  email doctor   neil.burman@gmail.com  or ph 6am to 9pm  0836299160. EMERGENCIES  cannot be dealt with- acute emergencies and trauma, bleeding cases  must go to any  Emergency Unit .

Billing according to means ie specialist professional rates:  eg as a preferred provider for Discovery Health-  consultation procedure  0190; for needy patients, what the medical scheme pays  Detailed medical report and advice protocol provided at R300. Even Hospital Plans have to pay for outpatient consultation for scores of PMBs ie Prescribed Medical benefit conditions like Menopause.

 Needy patients desiring brief consultation can be seen by arrangement at GP rate.    Bone density scan  (covered by some medical schemes)  procedure 3612..  Non-xray mammograms are not yet covered by medical schemes codes: R650 for SureTouch including clinical consultation, R800 for thermomammogram.

DOES PROGESTERONE SUPPLEMENT REDUCE FRACTURES? NO, BUT…

  neil.burman@gmail.com 

Question: Some say that ‘progesterone / progestins worsen bone loss’. everything I’ve read about progesterone says the opposite.   In fact Dr John Lee wrote a book about it.

Answer:    Most published stuff is rehash, opinion- not evidence. 

 Dont forget that Drs John Lee  & Kathy Dalton never did or published a trial, merely their opinions. They  wrote  books and articles based purely on subjective experience- and didnt have Medline to give them  evidence.. They   probably benefitted millions of women by advocating at least some safe progesterone cream replacement that was undoubtedly a lot better than nothing.  But all one can do from observations is formulate a theory, a hypothesis. Massive evidence is accumulating that all  men and women with low progesterone  should supplement with it to around a level of 1 -2 nmol/L   for immune and neuroprotective -benefits; – but to no clear benefit against fractures when used alone.

No significant reported  trials of progesterone or it’s synthetics that one can find, including from the top Osteoporosis reseach units in the world,  show benefit of any progestin on its own  on  fracture risk – if anything the contrary–   in postmenopausal women

At best, progesterone and androgenic progestins alone stop bone loss.

The only substances that safely and effectively reduce fractures and actually increase bone density  and muscle longterm in  simple safe lowcost combination – in both spine and hip –  at all ages are the natural anabolics – calmag, boron, zinc, manganese, copper, selenium, vits (B6,9, 12,C, D & K),  proline, glycine, creatine, lecithin, testosterone, estrogen and melatonin; and if deficient, iron (obvious in children and pregnancy); iodine and fluoride (regional deficiencies).

     [It is unclear from published trials whether adding strontium, biphosphonates, SERM, calcitonin,  parathyroid hormone , or  human growth hormone in HGH-deficient elderly patients,  further reduces fracture rates when added to appropriate essential supplements already listed above – this seems unlikely. and no Drug manufacturer is going to fund such a trial, which will likely only confirm the fruitlessness and risks  of their exensive patent drugs] . .

Estrogen at best stops bone loss- and in the WHI, reduced fractures by just below a third . When combined with progestin, th anti-fracture benefit was slightly reduced.

What matters is that only vigorous vit D & appropriate testosterone actually restore lost bone and muscle mass /  strength.

Bone density improvement on progesterone alone has been claimed, but there are no definitive studies in humans or animals to show this.

  We do know that the synthetic progestins if anything reduce bone density EXCEPT perhaps the androgenic progestins -which progesterone is not. !

  In the two arms of the giant Womens’ Health Initiative, in well-matched women, compared to placebo, premarin alone reduced all fractures by 29% (and hip fractures by 35%)  whereas premarin + progestin reduced all  by only 23% (and hip fractures by 33%) .

In the PEPI and the Lydeking-Olsen trials, progestins at least stopped fall in bone density- but only in the WHI did estrogen reduce fractures- and progestin did not help further.

So where are the trials showing  that progesterone actually does reduce fractures? It will be great to see them.

However, in a landmark review that matches her study-of-the decade on the Perimenopause in 1998   (showing that that phase is in fact a time of estrogen excess) – Jerilyn Prior last month published with Seifert-Klauss  another  study-of-the-decade  showing that progesterone itself  is in fact a vital co-hormone in enhancing the bone-strengthening effect of estrogen provided they are given together continuously.

How much better against fractures  is estrogen+progesterone than estrogen alone?  There is still no objective data- but such a trial by Seifert-Klauss ea   is in progress. 

And given their increased cancer and cardiovascular risks, synthetic progestins ‘ theoretical bone benefits cannot be extrapolated to human progesterone.

But there is so much other evidence about the independent multisystem benefits of progesterone without estrogen – especially for its immune, anti-cancer and neuroprotective benefits- to make it obligatory for progesterone always to be prescribed with estrogen, irrespective of hysterectomy status.

Thus John Lee was wrong on progesterone alone against fractures, but correct for the combination of progesterone with estrogen giving better antifracture protection than estrogen alone. .

update: ACQUIRING/JUGGLING THE BEST SEX HORMONE HRT REGIME FOR WOMEN.

Joey Basson writes January 28, 2010

I used Primogyn Depot for about 20 years, but I believe it has been discontinued in South Africa. I am now really struggling to find something that really works for me.

The injection was perfect. Do you have any suggestions?

reply: Hi Joey,
DRUG COMPANIES GANG UP  TO SUPPRESS CHEAP EFFECTIVE AGENTS -AS THEY DID FOR 25 YEARS EACH WITH LITHIUM AND METFORMIN IN USA, STILL BLOCKING HUGELY BENEFICIAL USE OF CANNABIS; AND  at the end of 2008, without notice or warning,  they conspired to abolish  CHEAP APPROPRIATE  NON-ORAL HRT IN RSA- the depot injections MIXOGEN, DEPOTRONE, even PRIMODIAN DEPOT, PRIMOGYN DEPOT.

NOW APPROPRIATE NON-ORAL HRT COSTS ALMOST 5 TIMES AS MUCH TO USE, AS eg CREAMS, PATCHES, SPRAYS, IMPLANTS FOR BOTH MEN AND WOMEN- AND FOR WOMEN WITH FAR MORE BOTHER.

Now the only way we are going to get such injections back in RSA is if there is enough interest to fight through the red tape to import from overseas. But South African administration is now so degenerate   under the corrupt  Zumas that it takes 2 years to get desperately needed doctors and sisters registered here – and who cares about appropriate HRT for the aging? Certainly not the notorious “doctor” or “Rev”  Zumas since they dont give a fig for evidence or human -especially  the poor and womens’-  rights..

if you live too far away, we can do a personal consult by email+- phone +- skype – via the necessary questionnaire by email- for you to discuss and implement with your local GP.

see numerous updates the past year at  https://healthspanlife.wordpress.com/?s=HRT

22 March 2009

An update review by Barry Wren from an Australian Menopause Clinic again debunks the myth that appropriate HRT in postmenopausal women PMW increases the risk of breast cancer, cardiovascular  disease CVD and thrombosis. It  stresses that “benefits of HRT include  less:  symptoms of menopause;  osteoporotic fractures,  ischaemia and cardiovascular-related death, forgetfulness, dementia and colorectal cancer; and  improved well-being, quality of life,  vagina, sexual enjoyment and bladder capacity,  with increased longevity. Oral  OHT doubles the risk of thromboembolism”. But on it’s own  in the young women in the Womens’ Health Initiative, oral equine estrogen (premarin)  reduced all major risks even new breast cancers and death from breast cancer.

As we hear regularly in women who have unwisely followed hysterical advice to stop HT,  stopping appropriate HT leads to fairly rapid loss of many of the above benefits. It has been  obvious for a century if not millennia   that permanent appropriate Human Hormone Replacement HRT of any of the dozens of our hormones that run out   is  (like a complete supplement of all the vitamins, minerals and the biologicals other than HRT)  prudent if not essential.

But we have to understand the reasons, risks and different regimes available. Nobody may prescribe or administer any sex HT Hormone Therapy without the necessary up-to-date training and experience, ensuring that the patient is having the necessary periodic examinations to ensure both safety and that the SHRT is appropriate. So patients must not self-treat with over-the-counter  supplements.

But only doctors and pharmacists who have costly current dispensing licenses may dispense and compound any hormone creams. And oral HT including phyto/plant hormones are  under suspicion of promoting cancer long term, let alone hepatic first pass effects like thrombosis and gallstones, and fluid retention oedema and hypertension (Genazzani ea 2008) .

INJECTION: tiny safe self-injection of combined hormone subcutaneously  (like insulin) is easy every one to three weeks, as most men use for HRT.  Monthly injection of depot preparations that last about three weeks  is not advised for anyone, especially not women with a womb as they are liable to have break-through periods. But unlike men, many women prefer to use hormone creams daily. The Depot hormone injections have climbed in price – what is now available averages about R75 per month. BUT (unless she gets the injection from her doctor regularly & proportionately every 1 to 3 weeks), women have to lay out about R1000 for self-injection (since  pharmacists will not likely  split a multi-vial or a set of three vials).

Provided that they ensure that they are appropriately trained in such therapy, all doctors are licensed to give periodic chronic injections – which should always be exclusively by tiny subcutaneous injection to avoid the notorious ie potentially crippling complications of intramuscular injections. But if nothing else is required, doctors are entitled to charge about R100 fee for the responsibility of an injection visit. Like insulin, patients easily learn to give it themselves- for men about 160mg depot-testosterone every 2wks (as opposed to 1gm testosterone undecanoate Nebido every 3 months- or about 1/10th of the male dose for women deficient in testosterone).

Synthetic ie xenohormones – those not normally produced by humans- eg progestins, ethinylestradiol-  may be invaluable (although by no means essential)  for birth control; but should not be used for PMW, especially not orally.

USING CREAMS: it is indeed best for women to (initially) juggle the balance of the three hormones  (all of which are made to the highest standard in South Africa)  until you have determined what ratio and quantity suits you best.

For the slim small older woman who needs both hot flash control and energizing, memory, ache relief:  the first priority is to control hot flashes, skin & hair without arousing breast and womb discomfort:

so try the 0.25% Bies(trogen) (E2 + E3- usually 1:4 ratio)  initially 1/2 ml scoop 1 – 2 x/day with the progesterone 3% cream initially just ¼ to 1/3 ml scoop a day ie 4 to 1 or 3:1 . This is ideally rubbed into the face as makeup- or if you like, dilute them in simple aqueous cream. Increase the combined dose to double if necessary to get control of the flashes – but the higher the Biest dose, the higher the risk of waking the breasts and womb, or getting thrombosis and ankle swelling.

And (unless your androgen level is still high) use just enough Testosterone cream 0.5% eg 1/2 to 1 scoop once (or twice) a day – below the waist ie vaginally or between the thighs or on the soft sole of the foot – to energize, improve alertness, libido, muscle and bone strength. Supplementing estrogen and progesterone alone may suppress necessary androgen.

In the bigger plump younger woman, who desires memory, energy, fat loss and libido rather than hot flash and skin improvement, using testosterone below the waist and progesterone on the face in the above gradually increasing doses often suffices, without the fattening and breast-womb arousing risks of extra estrogen. Such women often make enough estrogen from testosterone and in their excess fat stores.

But once the average women is well past 60yrs, low-dose estrogen often becomes advisable anyway for balance.

Old women benefit from and tolerate perhaps 1/6th to 1/10th the doses of appropriate balanced  human sex hormones of younger women.

THE THREE PRIME HUMAN SEX HORMONES: there are no risks from any appropriate HRT, only risks from avoiding it. Progesterone alone lacks some of the benefits of testosterone and estrogen eg on muscle- bone and hearing. Of the three hormone types, only androgen protects and improves muscle mass and strength. Testosterone excess (hairy face, acne, anger, clitoris growth, husky voice) is easily avoided with sensible balanced dose adjustment. Progesterone and testosterone have major benefits that estrogen may lack eg on hyperimmunity and inner hostility- issues that may not concern the gyne surgeon.

(Bi)Estrogen excess-  especially if used  alone-  does the reverse (of testosterone): promotes endometriosis and breast activation; excess actually weakens muscle eg bladder leak by melting collagen; it fattens; has little benefit directly on depression (although it does reduce dryness and pain); may promote thrombosis since unlike testosterone it does not diminish clotting; and may promote anxiety, hostility- this is why progesterone cream is often the best for monthly PMS and for perimenopausal anxiety (against the raging hostility from estrogen swings).

Above all else, remember that estrogen stimulates both breasts and womb- so estrogen must always be balanced by enough progesterone and(/or) testosterone. And if the hormones are allowed to run out by widening the gap between injections beyond two weeks, or between cream doses by more than two days, vaginal bleeding likely will occur.

The initial outlay cost of the three different hormone creams is up to R500 retail- you find out for yourself how long each tub lasts; as opposed to having an experienced pharmacy eg the manufacturing AntiAging pharmacy in Gauteng  compound ie mix what you want in one or two tubs that will last a few months. Try your local pharmacy – but finding one with experience is difficult.

PREVENTION? OR WAITING FOR DISEASE FROM NEGLECT TO CRIPPLE YOU? Many  gynecologists (like urologists) are primarily surgeons concerned with reproduction, menstrual, pelvic and cancer problems, and treat the menopause years often with fattening hormone pills (HT- which have more risks) and surgery..  They do not have to deal with the much wider irreversible medical problems of old age (obesity-diabetic, insulin resistance, lipidemia, vascular, immune, fracturing, arthritic, visual and hearing loss,  depression, and dementias – and no least, common sudden premature death)# – which are largely AVOIDABLE with appropriate natural supplements from the beginning, including balanced non-oral human sex hormones. As a BBC news report this month  says, memory (ie cellular) deterioration  begins on average  before age thirty.

It is not the gynecologist, but patients  and Family/ general practitioners GPs and specialist physicians including endocrinologists and geriatricians who have to deal long term and medically (not surgically)  with these easily preventable crippling killer diseases..  Surgery cannot address the basic pathogenic cause of chronic degenerative disease.

The discomfort and fattening of the 5-10 MENOPAUSE years is a concern for all doctors – and the earlier the menopause (whether natural or surgical), the more important it is to start appropriate simple balanced non-oral HRT and other effective medical prevention of fattening and diabetes eg other insulin sensitizers like metformin. Avoiding the late postmenopausal  silent killer degenerative diseases of aging (# above) is crucial  essential duty of doctors – but mostly of patients themselves,  since- obstetrics and trauma  aside-  most doctors earn more by disease than by prevention..

ndb

What evidence is there that higher Testosterone Levels in Women CAUSE Obesity, I.R., Metabolic Syndrome, CVD or Cancer?

neil.burman@gmail.com

A new paper (Patel 2009) says   Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular disease CVD  risk factors; so  to test whether higher T levels  associate with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) , ie whether this translates into increased CVD later in elderly women,    ultrasensitive testosterone T  assays were used  in 344 women aged 65–98 yr enrolled in the Cardiovascular Health Study CVH,  with cross-sectional analyses..   They found a stepwise increase in  IR with increasing total (P = 0.0.003) and free T (P = 0.02) level. In adjusted models, higher levels of both total and free T  strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, free T was NOT significantly associated with MetSyn or CHD.

This CVH study was in 5201 folks from 65-101yrs  ie mean age ~72yrs . They  were overweight – mean waist 93cm, BMI 26kg., +- 25% with metabolic syndrome.

What clinical relevance  does this crossectional observational study have  in management of postmenopausal women PMW?  Observational studies say nothing about cause and effect.

The alarming finding from   that CVH  study is that the more frequent the use of aspirin  , the higher the rate in women of ischemic stroke (O.R 1.6) but especially hemorrhagic stroke (O.R 4.0) . SO ELDERLY  WOMEN SHOULD NOT BE PRESCRIBED ASPIRIN-   stick to fish oil and EDTA.

We have known for   decades that increasing obesity  in women  associates  with increasing estrogen (from fat) and testosterone (from ovaries). – as in PCOS, as in PMW, the only effective endogenous defence mechanism women can mount against increasing obesity (and thus insulin resistance, prediabetes)  is to increase luteal testosterone output -ie it requires ovaries..

But the overwhelming positive spinoff from CVH is  that the higher the anabolic hormone (testosterone and  vit D) levels ,  the greater their strength and  ( 2/3)  reduction in falls– with the extra vitamin D3 further reversing obesity. Falls  are the greatest risk factor for fractures. .

OVARIAN CANCER? A year ago a Queensland group (Olsen ea) found that Women who had ever used testosterone supplements had a a 3.7fold  increased risk of ovarian cancer;” but they make no claim about cause and effect. In 1591 cases with ovarian malignancy they found only 11 who gave a history of testosterone use, compared to 4 of 1501 controls who had used testosterone, but they gave no breakdown on how many used physiological ie safe  parenteral balanced  physiological testosterone as opposed to unphysiological ie risky exposure. As they concludeIn summary, we found no consistent evidence for a role of androgens in the aetiology of ovarian cancer, overall or by subtype, and thus our findings do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.”

As opposed to virilizing ovarian tumours which secrete excess testosterone, the rarity of testosterone causing ovarian cancer is illustrated by there being only 3 cases reported of  ovarian cancer in a female-to-male transsexual treated with male dose testosterone (Dizon  2006, Hage ea 2000.) despite the increasing use of testosterone for such gender change let alone for female androgen insufficiency in women with ovaries. However, Louis Gooren’s group did describe in 1991  PCOS-changes in the ovaries removed at hysterectomy after a mean of 21 months of testosterone therapy in 12 of  17  female to male transsexuals. Unsurprisingly, no cases have been reported of women athletes developing ovarian cancer after years of testosterone abuse – presumably such reports were suppressed in the Eastern Block countries where such ruthless  practice was rife.

.Despite the fact that  obesity is  now endemic, associated with numerous diseases, especially vascular disease,  diabetes and  cancer, and that PCOS is by far the commonest associate of female hyperandrogenism, there is no evidence that PCOS ie  spontaneous hyperandrogenism is associated with increase in any cancer.  This suggests that moderate hyperandrogenism in women  is indeed protective against cancer since it mitigates the cancerogenic effect of obesity and diabetes.

2 years ago Braunstein from the Cedars-Sinai reported “a significant relationship  between total and free T and the presence of coronary artery disease after adjustment for the effect of E2“.  Similarly, no evidence is adduced for cause and effect. Observed subjects were very high  risk-  mean age 65yrs, obese (mean BMI 30kg),  70% on aspirin, and half had had hysterectomy.  As they conclude “One potential problem with the current study is that the results were obtained in a highly selected group of women undergoing coronary angiography for suspected ischemia and who had a high CAD risk factor burden, raising the possibility that these findings may not be relevant to broader groups of women.”

No studies and no clinics on any continent  have ever reported link  between balanced physiological parenteral depot testosterone (up to ~10mg/week) – depot estradiol  replacement  (up to ~1mg/week) and increase in any cancer  or IR, Met Synd, and CVD  on  balanced  T replacement  in women with relative T/E   deficiency.  The same goes for the use of appropriate parenteral physiological testosterone replacement in men with testosterone deficiency. .

So thus  far there is no evidence  that the natural higher serum T concentrations within the range found  in younger or older women (up to ~6nmol/L) CAUSE overweight/ obesity Insulin Resistance, Metabolic Syndrome, cardiovascular disease or cancer. This is not surprising since our experience bears out the extrapolation to women from the data of Nieschlag and Behre (1991 et seq)  that testosterone level after the proportionate  depotestosterone cypionate or enanthate  ~10mg dose sc/ week will average around 2.4nmol/L .