Can anti-Müllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation?

The ability to predict the response potential of women to ovarian stimulation may allow the development of individualized ovarian stimulation protocols. This tailored approach to ovarian stimulation could reduce the incidence of ovarian hyperstimulation syndrome in women predicted to have an excessive response to stimulation or could improve pregnancy outcomes in women classed as poor responders. Namely, variation of the type of gonadotrophin-releasing hormone (GnRH) analogue or the form and dosage of gonadotrophin used for stimulation could be adjusted according to an individual's response potential. The serum concentration of anti-Müllerian hormone (AMH) is established as a reliable marker of ovarian reserve, with decreasing concentrations correlated with reduced response potential. This review examines the current evidence evaluating individualized ovarian stimulation protocols using AMH concentration as a predictive marker of ovarian response. The rationale behind why specific treatment protocols based on individual response potential may be more suitable is also discussed. Based on current evidence, it appears that the use of AMH serum concentrations to predict ovarian response and optimize treatment strategies is a promising approach for improving pregnancy outcomes in women undergoing ovarian stimulation. However, prospective randomized controlled trials evaluating this approach are needed before any firm conclusions can be drawn.

Ovarian stimulation: is there a long-term risk for ovarian, breast and endometrial cancer?

Adverse effects have been related to infertility treatments. Infertility in general, and female infertility in particular, is a well established risk factor for cancer development, especially ovarian, breast and endometrial cancer. This article addresses the possible association between infertility and cancer development, with an emphasis on the influence of infertility treatments, through a meticulous search of the literature published thus far. While results regarding the possible association of infertility, ovulation induction medications and invasive ovarian cancer show no increased risk and are reassuring, results for increased risk for breast cancer and endometrial cancer following exposure to ovarian stimulation medications are inconclusive. Larger population studies with longer periods of follow-up and better adjustment for confounding factors are needed.

The nutritional pattern of frailty - Proceedings from the 5th Italian Congress of Endocrinology of Aging, Parma, Italy, 27-28 March 2009.

Frailty has become one of the 'hot spots' in geriatric research. Frailty has multifactorial origin, and is regarded as a fundamental risk factor for deteriorating health status and disability in elderly people and is highly prevalent in the population above the age 65. It is estimates that prevalence rates up to 27% and pre-frailty rates up to 50% qualify for the term "epidemic". Although the role of nutritional deficiency in the development of age-related frailty was suggested long ago, research conducted in this area is relatively recent. The critical role of micronutrients in this context suggests the need to improve the quality of food eaten by elderly people whereas quantity of food appears to be less relevant. This review summarizes the recent literature on the nutritional pathways to frailty with particular focus on the effect of energy, protein and micronutrients.

ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males.

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.

Infertility, ovulation induction treatments and the incidence of breast cancer--a historical prospective cohort of Israeli women.

CONTEXT: Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive. OBJECTIVE: To evaluate the association between infertility, exposure to ovulation induction drugs and the incidence of breast cancer. DESIGN: Historical prospective cohort and nested case-control study. SETTING: Institutional practice PATIENTS: About 5,788 women attending five infertility centers in Israel between 1964 and 1984. INTENTION: Abstracting of medical records and telephone interviews. MAIN OUTCOME MEASURE: Breast cancer incidence was determined through linkage with the National Cancer Registry database. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing the observed to the expected cancer rates in the general population. In addition, a nested case-control study within the cohort was performed with interviews of breast cancer cases and two matched controls. RESULTS: The study cohort included 120,895 women years of follow-up. Compared to 115.2 expected breast cancer cases, 131 cases were observed (SIR = 1.1; 95% CI 0.9-1.4). Risk for breast cancer was significantly higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0-1.8). Similar results were noted when comparisons were carried out between treated and untreated women, and when multivariate models were applied. In the nested case-control study, higher cycle index (OR = 2.2; 95% CI 1.0-4.8) and treatment with clomiphene citrate (OR=2.7; 95% CI 1.3-5.7) were associated with higher risk for breast cancer. CONCLUSION: Infertility and usage of infertility drugs in general are not associated with increased risk for breast cancer. However, for infertile women treated with clomiphene citrate, breast cancer risk is elevated.

Endocrinology of the aging male.

Despite enormous medical progress during the past few decades, the last years of life are still accompanied by increasing ill health and disability. The ability to maintain active and independent living for as long as possible is a crucial factor for ageing healthily and with dignity. The most important and drastic gender differences in aging are related to the reproductive organs. In distinction to the course of reproductive ageing in women, with the rapid decline in sex hormones expressed by the cessation of menses, men experience a slow and continuous decline. This decline in endocrine function involves: a decrease of testosterone, dehydro epiandrosterone (DHEA), oestrogens, thyroid stimulating hormone (TSH), growth hormone (GH), IGF1, and melatonin. The decrease of sex hormones is concomitant with a temporary increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition sex hormone binding globulins (SHBG) increase with age resulting in further lowering the concentrations of free biologically active androgens. These hormonal changes are directly or indirectly associated with changes in body constitution, fat distribution (visceral obesity), muscle weakness, osteopenia, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. The laboratory and clinical findings of partial endocrine deficiencies in the aging male will be described and discussed in detail. With the prolongation of life expectancy both women and men today live 1/3 of their life with endocrine deficiencies. Interventions such as hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing the preventable and delaying the inevitable.

ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: scientific background and rationale.

Prescription sales for testosterone products have substantially increased over the last several years reflecting the growing awareness of physicians for the potential benefits of testosterone replacement therapy in men with hypogonadism. Indiscriminate administration of testosterone poses a risk and has to be deprecated. Testosterone supplementation to treat late-onset hypogonadism (LOH), a term for androgen deficiency in elderly men, is still controversially discussed mainly due to a lack of large, controlled clinical trials on efficacy and safety. To provide guidance for physicians primarily dealing with aging men, ISSAM is periodically updating and publishing its recommendations as new data become available [Morales A, Lunenfeld B. International Society for the Study of the Aging Male. Investigation, treatment and monitoring of late-onset hypogonadism in males. Official recommendations of ISSAM. International Society for the Study of the Aging Male. Aging Male 2002;5:74-86 and Morales A, Lunenfeld B. Androgen replacement therapy in aging men with secondary hypogonadism. Draft recommendations for endorsement by ISSAM. Aging Male 2001;4:1]. Following a panel discussion at the 4th ISSAM Congress in Prague in February 2004, the International Society of Andrology (ISA), the International Society for the Study of the Aging Male (ISSAM) and the European Association of Urology (EAU) revised existing recommendations on the definition, diagnosis and management of LOH. The recommendations are based on the currently available scientific data on androgen supplementation therapy and should be regarded as provisional until larger-scale, long-term studies are available. While certainly not intending to be exhaustive, this review will highlight some relevant background information and provide the underlying scientific rationale for the ISA, ISSAM and EAU recommendations on LOH published in this issue.

Serum testosterone measurement in men: evaluation of modern immunoassay technologies.

Accurate measurement of serum testosterone (T) is essential for proper diagnosis of androgen deficiency. There are now several modern assay technologies, including automated ones, for measurement of T. In this study, we compared analytical performance of five modern immunoassay technologies commonly used for measurement of total T: Vitros ECi (Ortho-Clinical Diagnostics; normal range (n.r.) 4.6-34 nmol/L); Architect (Abbott Laboratories; n.r. 9.7-34 nmol/L); Access (Beckman Coulter; n.r. 5.3-23 nmol/L); Delfia (Perkin-Elmer; n.r. 9.3-34 nmol/L); and manual EIA DRG kits (n.r. 8.3-42 nmol/L), with the classical RIA (3H-T), after extraction (n.r. 11-33 nmol/L), as a reference method. Total T was measured using all above-mentioned methods in serum samples from 100 male patients, aged 16-65 years. Mean T concentrations in these 100 serum samples assayed by all non-isotopic methods were statistically significantly higher than those obtained by RIA. Delfia showed the highest T levels (19.3 nmol/L versus 12.1 nmol/L by RIA) with a positive bias 60-100%. Almost similar results were obtained using Architect, with a positive bias 40-70%. The closest correlation in results was found between Vitros ECi and RIA (12.7 nmol/L versus 12.1 nmol/L). In the studied samples, the median of differences ranged from minimal (-0.4 nmol/L for Vitros ECi) to maximal (-7.25 nmol/L for Delfia). For all non-isotopic methods, with the exception of Vitros ECi, differences in subjects with low T level (< 10 nmol/L) were statistically significantly larger than in the subjects with high T (T > 10 nmol/L). All other methods showed different degrees of dissimilarities with the RIA, especially in the range of low testosterone concentrations, which is of importance in the clinical assessment of women and pubertal boys.

Infertility in the third millennium: implications for the individual, family and society: condensed meeting report from the Bertarelli Foundation's second global conference.

Primary infertility is a key issue in the developed world, while the developing world has high rates of secondary infertility. The impact of HIV/AIDS on fertility is insufficiently explored. One of the most important barriers to access to infertility treatment is cost; at the same time the role of social and cultural factors in restricting access should not be underestimated. IVF has become the standard therapy for female infertility, and ICSI for infertility of the male partner. However, the use of these therapies should not be initiated without a thorough investigation and, whenever possible, individual diagnosis of the underlying causes of infertility. Multiple gestation remains one of the most challenging and controversial issues in the treatment of infertility. Current IVF practices are often blamed for this; in this respect, attention should also be focused on the role of ovarian stimulation in ovulation induction. National guidelines and national registries for assisted reproductive technology (ART) are becoming more widespread and are expected to play an important role in promoting best practice in ART in the future.

Towards less confusing terminology in reproductive medicine: a proposal.

The use of the term "infertility" and related terms in reproductive medicine is reviewed. Current terminology is found to be ambiguous, confusing and misleading. We recommend that the fertility investigation report of a couple should consist of statements concerning description, diagnosis and prognosis. The description concerns the duration of non-pregnancy before consulting the clinician. A system for prognostic grading is proposed. The fertility investigation report forms the basis for further action, including the possibility of waiting with treatment in case of almost normal or only slightly reduced fertility. The use of the terms infertility, subfertility and fecundity is not necessary, and it is recommended to avoid them.

The ageing male.

With prolonged life expectancy, men and women can expect to live one-third of their lives with some form of hormone deficiency. The ageing male, in particular, has the added problem of developing urological diseases, such as benign prostatic hyperplasia (BPH), prostate cancer, continence disorders and erectile dysfunction. When discussing age-related problems, it is often difficult to separate and to distinguish between the natural ageing process, ageing amplifiers and an acute or chronic illness, or inter-current diseases. Partial endocrine deficiencies of ageing are associated with a decrease in the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEA-S), growth hormone, insulin-like growth factor and melatonin. There is also a concomitant increase in luteinising hormone and follicle stimulating hormone. The concentration of free biologically active testosterone is lowered further by an increase in sex hormone binding globulin (SHBG). Hormonal changes in the ageing male are associated with changes in the body mass index, osteoporosis, sleep and mood disorders. A number of testosterone replacement therapies are available. These therapies should maintain physiological levels not only of serum testosterone, but also of its metabolites, including dihydrotestosterone (DHT) and estradiol. Men on testosterone therapy should be monitored at 3-month intervals during the first year of use and, thereafter, at 1-year intervals if they are stable. The association of testosterone replacement with development of prostate cancer has not been determined.