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Declining semen quality and increasing incidence of testicular cancer: is there a common cause?

Male reproduction has been given little attention in science and in medical practice. However, a recent metaanalysis on semen quality, which clearly pointed to a decrease over the past 50 years, has been repeatedly quoted. Three recent reports have found that semen quality has declined among candidate semen donors during the past 20 years. The evidence of decline in the quality of semen is not the only indicator that the human testis is at risk. During the past 50 years, cancer of the testis has also become more common. This is a disorder of young men, and it is associated with a high rate of other abnormalities of the testis including undescended testis and poor semen quality. Furthermore, the incidence of both hypospadias and undescended testis has been reported to be rising in the general population. We believe that the evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders of men. However, the etiology is unknown. A recent hypothesis that links the trends in the health of the male reproductive system to xenoestrogens in the environment is discussed.

Adult↗

Limbic seizures alter reproductive function in the female rat.

PURPOSE: Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction. METHODS: Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. RESULTS: Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P4 administration restored cyclicity in all five sham-kindled controls that had spontaneously stopped cycling. P4 treatment to kindled females in PVC resulted in a different endocrine profile than that in non-P4-treated, kindled rats in PVC. P4-treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers. CONCLUSIONS: Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.

Amygdala↗

Gender-specific considerations in the treatment of mood disorders in women across the life cycle.

Major depressive disorder in women is a significant health concern. Rates of depression in women are approximately twice those seen in men. Observations of gender-based differences in prevalence, presentation, and treatment response in depression raise questions about the underlying causes of such differences. In addition, the specific factors that predict vulnerability to reproductive-associated mood disturbance, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal mood disturbance, remain to be delineated. While a growing amount of controlled data is emerging that describes response to treatment in women who suffer from these disorders, further investigation is needed to identify subgroups of women who are most at risk for depression and to define the most effective treatments for these patients.

Adult↗

Polycystic ovary syndrome: the influence of environmental and genetic factors.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Collagen↗

More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders.

In women, menorrhagia may be the most common manifestation of a bleeding disorder, but it is not the only reproductive tract abnormality that women with bleeding disorders experience. Women with bleeding disorders appear to be at an increased risk of developing haemorrhagic ovarian cysts and possibly endometriosis. As they grow older, they may be more likely to manifest conditions, which present with bleeding such as fibroids, endometrial hyperplasia and polyps. Women with bleeding disorders are more likely to undergo a hysterectomy and are more likely to have the operation at a younger age. During pregnancy, they may be at greater risk of miscarriage and bleeding complications. At the time of childbirth, women with bleeding disorders appear to be more likely to experience postpartum haemorrhage, particularly delayed or secondary postpartum haemorrhage. Vaginal or vulvar haematomas, extremely rare in women without bleeding disorders, are not uncommon. While women with bleeding disorders are at risk for the same obstetrical and gynaecological problems that affect all women, they appear to be disproportionately affected by conditions that manifest with bleeding.

Abortion, Spontaneous↗

Congenital malformations, reproductive wastage and consanguineous mating.

A study was undertaken in Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, South India, to understand the relation between congenital developmental disorders and consanguinity and also reproductive wastage and consanguinity. Four hundred children with existing congenital developmental disorders were studied with regard to their consanguineous parentage and compared with 1,000 randomly selected patients attending the paediatric outpatient department. There was a significantly higher prevalence of consanguinity in the study group (p < 0.001) and greater frequency in rural areas. The common types of consanguineous marriages were between first cousins (50.6%) and uncle and niece (42.4%). Frequency of consanguinity was not significantly related to religion and caste. The mean coefficient of inbreeding was 0.056. Consanguinity had no significant effect on average pregnancy rate and reproductive wastage. The frequency of consanguinity was significantly higher especially with autosomal recessive disorders (p < 0.001), congenital heart diseases (p < 0.001), multiple malformations (p < 0.001), neurological malformations (p < 0.005), chromosomal disorders (p < 0.01), genitourinary disorders (p < 0.02) and mental retardation-developmental disorders (p < 0.02). These observations stress the need for communicating the deleterious effects of inbreeding to the public through regular health education.

Abortion, Spontaneous↗

Energy availability, not body fatness, regulates reproductive function in women.

The morbid consequences of menstrual disorders in athletes require medical diagnosis and treatment. Reproductive disruption appears to occur when energy availability (dietary energy intake minus exercise energy expenditure) falls below a threshold between 20 and 30 kcal x kgLBM(-1) x d(-1), and some women may be more severely affected than others by subthreshold energy availability.

Body Composition↗

Alcoholism and antisocial personality. The sociobiology of an addiction.

Alcohol consumption may become adaptive from the evolutionary viewpoint when drinking settings and intoxication can be used to enhance the "cheating" reproductive strategy of antisocial personality disorder. This may explain the selective pressures leading to the association of familial alcoholism and antisocial personality disorder.

Adaptation, Physiological↗

The second law of thermodynamics is the first law of psychology: evolutionary developmental psychology and the theory of tandem, coordinated inheritances: comment on Lickliter and Honeycutt (2003).

Organisms inherit a set of environmental regularities as well as genes, and these two inheritances repeatedly encounter each other across generations. This repetition drives natural selection to coordinate the interplay of stably replicated genes with stably persisting environmental regularities, so that this web of interactions produces the reliable development of a functionally organized design. Selection is the only known counterweight to the tendency of physical systems to lose rather than grow functional organization. This means that the individually unique and unpredictable factors in the web of developmental interactions are a disordering threat to normal development. Selection built anti-entropic mechanisms into organisms to orchestrate transactions with environments so that they have some chance of being organization-building and reproduction-enhancing rather than disordering.

Biological Evolution↗

Exposure to hazardous substances and male reproductive health: a research framework.

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

Biomarkers↗

Reproductive options for individuals at risk for transmission of a genetic disorder.

The basis of human growth and development has long been considered to be one of the great mysteries of science and mankind. The portal to understanding this mystery was achieved by the Human Genome Project and Celera Genomics in 2001, with their joint announcement of the sequencing of 99% of the human genome map. Current reproductive options, however, remain restricted to the prevention of transmitting an at-risk gene or genes, but do not include treatment or cure. It is anticipated that this state of "halfway technology" will continue for years to come. As such, the scientific and ethical issues associated with each of these reproductive options will continue to affect the decision making of at-risk individuals. As the omnipresent health care provider, nurses have a duty to know and disseminate accurate and current information about reproductive options for individuals at risk for transmission of a genetic disorder. Nurses also have a duty to advocate for and ensure the privacy and confidentiality of genetic information.

Decision Making↗

Menstrual disorders in rural Gambia.

As part of a community-based reproductive morbidity survey in rural Gambia, the prevalence and association of menstrual disorders with sociodemographic characteristics and other reproductive morbidities, and with knowledge, attitudes, and beliefs concerning menstrual problems were assessed. A questionnaire was administered by a field-worker and by a gynecologist, who also examined the women. Semistructured interviews were conducted to assess knowledge, attitudes, and beliefs in a subsample. Of 607 menstruating women not using hormonal contraceptives, 16 percent complained to the gynecologist of irregular cycles, 14 percent of dysmenorrhea, 8 percent of spotting, and 4 percent of heavy or prolonged bleeding. Each complaint was associated with other reproductive morbidities. A minority of women with menstrual problems had sought health care, and menstruation was revealed to be a highly personal and secretive topic in this population. Menstrual disorders constitute an important unaddressed area of reproductive health service needs in developing countries for which relatively simple and inexpensive therapies are often available. Information, education, and support combined with clinical management of menstrual problems should be core elements of reproductive health programs.

Adolescent↗

[Does menstrual cycle affect mood disorders?].

OBJECTIVE: This paper will present a review of the literature on the relationship between the menstrual cycle and mood disorders. METHOD: We performed a MEDLINE search of the Turkish and English language literature for the years 1955-2005 using the following terms: depression, bipolar disorder, premenstrual syndrome, premenstrual exacerbation, premenstrual dysphoric disorder, menstrual cycle, and suicide. Earlier reports had shown higher psychiatric admission during premenstrual period of the menstrual cycle and higher prevalence of suicide attempts during specific phase of the menstrual cycle. RESULTS: Women of reproductive age with mental disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest that for a subset of women there is a relationship between phases of the menstrual cycle and increased vulnerability for an exacerbation of ongoing mood disorders (especially major depressive episode) or the development of a new episode. The question of whether the direction of mood shifts in the course of bipolar disorder is associated with specific cycle phase has been raised, albeit with limited and inconsistent data. CONCLUSION: There are a limited number of studies to elucidate these relationships and most of them lack prospective assessments, include the small number of patients and use unreliable methods of determining menstrual-cycle phases. Additionally, many reports do not specify whether the exacerbations reflect an aggravation of the underlying mood disorder or a new subset of symptoms that occur only during certain phases of the menstrual cycle. Further studies should provide more information about the contribution of premenstrual fluctuation or worsening to increased illness severity of mood disorder and treatment resistance.

Adult↗

[Limitations of reproduction medicine in male subfertility. Treatment of severe spermatogenesis disorders].

Treatment of severe male subfertility has become available since the intracytoplasmic injection of a single sperm into an oocyte was successfully applied for the first time in 1992. Moreover, also with the use of testicular spermatozoa for this procedure fertilization and pregnancies could be accomplished. This review addresses the development of these techniques and discusses achievements and problems as well as future aspects of the feasibility of early spermatid injection are stressed. Furthermore it includes the basic elements of spermatogenesis and the major concerns regarding the underlying genetic reasons for spermatogenic failure.

Chromosome Aberrations↗

Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus.

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. Recent prevalence estimates suggest that 5-10% of premenopausal women have the full-blown syndrome of hyperandrogenism, chronic anovulation, and polycystic ovaries. Evidence suggests that women with polycystic ovary syndrome have a unique disorder of insulin action and are at increased risk to develop non-insulin-dependent diabetes mellitus. Further, non-insulin-dependent diabetes mellitus in women with polycystic ovary syndrome has a substantially earlier age of onset (third to fourth decades) than it does in the general population (sixth to seventh decades). Studies assessing whether abnormalities in insulin action are intrinsic or secondary to the hormonal milieu have found that insulin-induced receptor autophosphorylation is markedly diminished in approximately 50% of polycystic ovary syndrome women. This defect is unique to women with polycystic ovary syndrome and is not seen in other common insulin-resistant states of obesity and non-insulin-dependent diabetes mellitus. In polycystic ovary syndrome women who have normal receptor autophosphorylation, it remains likely that signaling mechanisms downstream of the receptor are abnormal, since these women are also insulin resistant. This distinctive post-insulin-binding defect appears to be genetic, since it is present in cells removed from the in vivo environment for generations.

Anovulation↗

The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD).

Currently it is estimated that 3-8% of women of reproductive age meet strict criteria for premenstrual dysphoric disorder (PMDD). Assessment of published reports demonstrate that the prevalence of clinically relevant dysphoric premenstrual disorder is probably higher. 13-18% of women of reproductive age may have premenstrual dysphoric symptoms severe enough to induce impairment and distress, though the number of symptoms may not meet the arbitrary count of 5 symptoms on the PMDD list. The impairment and lowered quality of life for PMDD is similar to that of dysthymic disorder and is not much lower than major depressive disorder. Nevertheless, PMS/PMDD is still under-recognized in large published epidemiological studies, as well as assessments of burden of disease. It is demonstrated here that the burden of PMS/PMDD as well as the disability adjusted life years (DALY) lost due to this repeated-cyclic disorder is in the same magnitude as major recognized disorders. Appropriate recognition of the disorder and its impact should lead to treatment of more women with PMS/PMDD. Efficacious treatments are available. They should reduce individual suffering and impact on family, society, and economy.

Adolescent↗

Management strategies for male factor infertility.

Although modern assisted reproduction techniques contribute a lot to overcoming severe male factor infertility, application of these methods in every infertile couple would represent an over-treatment. Therefore, conventional treatment modalities are still the first approach to male fertility disorders. Apart from assisted reproduction techniques, these include surgical procedures and the administration of drugs. Causal treatment regimens of proven effectiveness are only available for patients with infertility resulting from hypogonadotrophic hypogonadism. Drug treatment of retrograde ejaculation is also effective. Inconsistent results have been obtained with empirical treatment including antiestrogens, androgens, aromatase-inhibitors, mast cell blockers, zinc and pentoxifylline. Anti-inflammatory and immunosuppressive therapy as well as treatment with antioxidants in the presence of reactive oxygen species has not yet been demonstrated to be effective by controlled studies but represent at least a rational approach which should be investigated more thoroughly. High dosage administration of follicle stimulating hormone aimed particularly at improving disturbed sperm structures, and the combination of tamoxifen with androgens, may be promising developments. A careful diagnostic work-up is necessary before any andrological treatment is commenced so that adequate treatment options can be selected for individual patients.

Adrenal Cortex Hormones↗