Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease

Objective.?To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women.

Methods.?Fifty surgically postmenopausal women were included in this double-blind, placebo-controlled and randomized study to receive daily oral treatment with estradiol valerate 2?mg + placebo (E/P) or estradiol valerate 2?mg + testosterone undecanoate 40?mg (E/T) for 24 weeks and then switched to the other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP), Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-α, Insulin-like growth factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1, and homocysteine were analyzed at baseline and after 6 and 12 months.

Results.?Estradiol and androgens increased as expected during the treatments. After 6 months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded, whereas IL-6, TNF-α, and homocysteine were unchanged. When testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone. However, testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6, TNF-α, and homocysteine.

Conclusion.?Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects. On the contrary, the estrogen-induced increase in hsCRP was suppressed.     

Hormone replacement therapy update: who should we be prescribing this to now?

PURPOSE OF REVIEW: To summarize results from the Women's Health Initiative trial and other recent randomized placebo-controlled trials of hormone replacement therapy, which fundamentally changed our understanding of its risks and benefits. RECENT FINDINGS: The Women's Health Initiative study for the first time provided evidence of harmful effects of hormone replacement therapy on the cardiovascular system and also confirmed significantly increased risk of breast cancer which was previously documented in a metaanalysis. Most recent studies indicate a particularly harmful effect of combined estrogen/progestin regimens in terms of increased breast cancer risk. SUMMARY: The effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, gallbladder, diabetes, cognitive function, health-related quality of life, colorectal cancer, osteoporosis and menopausal symptoms are discussed briefly. The emphasis is on providing concise clinical guidelines for hormone replacement therapy use in new circumstances. We also discuss some alternative therapeutic modalities for women who have menopausal symptoms, but contraindications for hormone replacement therapy.     

Hormone replacement therapy: time to move on?

The risks and benefits of hormone replacement therapy (HRT) need to be put in perspective. In the analysis of clinical trials, emphasis is often placed on relative risks, statistical significance and 95% confidence intervals, whereas, from a clinical perspective, more may be gained from a consideration of the absolute and attributable risks of therapy. The Council for International Organizations of Medical Sciences recommended that the frequency of adverse events be categorized as "rare" if less than 1/1000 but more than 1/10,000, and as "very rare" if less than 1/10,000. In the analyses of the Women's Health Initiative (WHI), the attributable risks were "appreciable" (i.e. more than 1/1000) only in women aged over 70 years, with the exception of the risks of venous thromboembolism and stroke. The women in the WHI trial do not represent the relatively younger, healthy, postmenopausal women most commonly prescribed HRT, who are probably at much lower risk. Moreover, the WHI trial did not take into account the benefit of relief of menopausal symptoms, which is, for many women, paramount and outweighs the "rare" long-term risks. Age may be a useful guide to risks and some simple guidelines for management, based on age, are suggested. Many women have been denied or have discontinued HRT because of the fear of risks, which may not have been put in perspective or fully understood. The care of postmenopausal women is not static, and sufficient has now been learned to enable each menopausal woman, with the help of her medical adviser, to come to a balanced and reasonable decision.     

Does hormonal replacement therapy actually protect against cardiovascular disease?

It is generally accepted that menopausal symptoms can be controlled by HRT. As additional (putative) benefits of HRT were discovered, it was claimed that such uses were also important. Soon, trials were instituted to test these assertions, some of them quite large and projected to last a long time (> or = 5 years). The most instructive for medical practice are the observational trials and, still more, randomized, controlled trials. Unfortunately, the results of these trials for both primary and secondary prevention of CHD are not in agreement, although the observational trials are mostly more favorable to the benefits of HRT on CHD. The present review considers both kinds of trials and their effects on primary and secondary CHD prevention. It also attempts to group the studies by their results and their implications for guiding patients in choices and decisions regarding HRT.     

Hormone replacement therapy and epithelial ovarian cancer: is there and association?

Recently it was estimated that about one-third of postmenopausal British women aged 50-64 years currently uses hormone replacement therapy (HRT) for treatment of climacteric symptoms and for other medical reasons. To reduce an excess risk of endometrial cancer induced by oestrogens, modern HRT regimens contain either sequential or continuous progestogens. The protective effect of parity and oral contraceptive use observed in the majority of epidemiological studies on epithelial ovarian cancer (EOC) suggest that hormonal factors are likely to operate in ovarian carcinogenesis. However, the studies where HRT was examined in relation to the risk of EOC have reported conflicting results. The objective of this epidemiological review is to evaluate the risk of EOC in relation to the use of HRT, with particular focus on the few studies where oestrogens and progestogens in HRT were assessed separately. Further, the findings regarding HRT and EOC risk will be discussed in the context of available aetiological hypotheses. Finally, any clinical implications are commented upon.     

Hormonal replacement therapy and cardiovascular risk: contra-indication or non-indication?

In the field of cardiovascular risk and treatment of menopause, only one instruction can be currently given to the prescribers: caution. Since the publication of heart and estrogen/progestin replacement study, the dogma of the cardioprotection induced by hormonal replacement therapy began to crumble. This paradigm had set up with observational studies, which for the majority had neglected in their retrospective analysis the socio-economic factor. Since shock caused by HERS, nine randomized studies are accumulated. All are negative, except for EPAT. At present, all confirms the prophetic recommendation of J.E. Rossow, in 1996: "Putting the brakes on the bandwagon". The last guidelines formally prohibit HRT in coronary women or with the aim of primary prevention of chronic conditions in healthy postmenopausal women.     

Ischemic placental syndrome – prediction and new disease monitoring

The last decade has seen an improved understanding of the cause of the development of pathologies such as gestational hypertension, preeclampsia, intrauterine growth restriction, intrauterine fetal death or placental abruption. Nowadays, we know that most conditions within this group share the same pathogenesis, the cause of which is placental ischemia. The following review is an attempt to propose a new method for prediction, diagnosis and – above all – appropriate monitoring of pregnant women and fetuses developing the ischemic placental syndrome with the use of tests that are new but yet widely available in clinical diagnosis. They are closely related to the condition’s pathogenesis, therefore their elevated levels may predate clinical symptoms, and – most importantly – they correlate with syndrome aggravation and the occurrence of complications. Perhaps, the new look will allow us to improve perinatal results by reducing mortality and severe complications in pregnant women and fetal deaths resulting from sudden intrauterine fetal death or placental abruption.     

Raspberry leaf – Should it be recommended to pregnant women?

This review evaluates the safety and efficacy of raspberry leaf (Rubus idaeus) in pregnancy. The electronic databases PubMed, ISI Web of Science, AMED, EMBASE, Natural Medicines Comprehensive Database and Cochrane Library were searched. Altogether 12 original publications with focus on safety or efficacy during pregnancy, pharmacology and in vitro tests explaining mode of action or constituents in Rubus idaeus were reviewed. Limited documentation exists and part of it is 50 years old or older. Only the latest animal study indicates an increased risk for the unborn child; however, all the studies are small and cannot rule out negative effects on pregnancy outcome. The efficacy of raspberry leaf is not convincingly documented.The use of raspberry leaf in pregnancy is a traditional herbal therapy and is recommended by some midwives. Due to the lack of evidence for safety and efficacy such recommendations are questionable.Suggestions for future work are given.     

Obstetrics and gynecology--to be or not to be? Factors influencing one's decision

OBJECTIVE: The study was undertaken to determine factors influencing a medical student's decision to choose obstetrics and gynecology (OB/GYN) versus another specialty. STUDY DESIGN: Medical school graduates from 1991 to 2001 were surveyed about factors influencing their specialty choice. Data were analyzed with chi(2), logistic regression, and odds ratio where appropriate. RESULTS: Of 1128 surveys, 562 (50%) were returned; 37% of respondents were women and 63% were men; and 73 (13%) chose OB/GYN. Statistically significant positive influences included student sex, second-year rotations, OB/GYN staff, continuity of patient care, primary care opportunities, surgical opportunities, healthy patient population, female patients, lifestyle, and financial opportunities. CONCLUSION: Perceived lifestyle, primary care opportunities, and malpractice concerns did not influence the choice to enter the field of OB/GYN. Also, the perception of patient's desire for female physicians had no apparent influence, either positive or negative, in the decision process.