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PubMed1981

Reproductive wastage and developmental disorders in relation to consanguinity in south India.

The effect of consanguinity on fertility, reproductive loss and developmental disorders were studied in 156 consanguineous marriages in comparison with 221 non-consanguineous marriages. Although fertility was greater (P less than 0.05) in consanguineous than in non-consanguineous marriages, the number of living children were approximately equal in both groups, on account of increased child mortality in the former (P less than 0.05). The frequencies of abortion and stillbirth were (also) approximately equal in both groups. Developmental anomalies were significantly more frequent (P less than 0.001) among the offspring of consanguineous parents. These results indicate the continued presence of deleterious genes in this population, in spite of the practice of consanguinity over many generations.

Abortion, Spontaneous↗
PubMed2005

Longitudinal evaluation of reproductive function in women treated for bipolar disorder.

BACKGROUND: We assessed reproductive endocrine and metabolic markers in women treated for bipolar disorder over a 2-year time period, controlling for valproate use. METHODS: Twenty-five women ages 18-45 with bipolar disorder underwent longitudinal evaluations. Subjects completed a reproductive health questionnaire and endocrinological exam at baseline. Total and free testosterone, progesterone, LH, FSH, fasting insulin and glucose, and other hormones were measured across the menstrual cycle at baseline and at 2-year follow-up. RESULTS: Ten subjects were currently receiving valproate as a mood stabilizing agent; of the remaining subjects, six received lithium and five received atypical antipsychotics. Of all subjects, 41.7% reported current oligomenorrhea, while 40% reported oligomenorrhea before starting medication. Rates of oligomenorrhea and clinical hyperandrogenism did not differ by medication use. Eighty percent of women had a high homeostatic model assessment of insulin resistance (HOMA-IR) at baseline; all other measures were normal. Over time, all subjects exhibited a significant decrease in luteal phase progesterone and increase in free testosterone concentrations. Valproate use was associated with an increase over time in total testosterone. Baseline values and changes in BMI were similar across groups. LIMITATIONS: Limitations include small sample size and the absence of a control group. CONCLUSION: We confirm our previous observations of high rates of menstrual abnormalities, hyperandrogenemia and insulin resistance in women with bipolar disorder. These results tentatively support the role of valproate in hyperandrogenemia; however, rates of oligomenorrhea and clinical hyperandrogenism did not differ between medication groups.

Adolescent↗
PubMed2000

Valproate, hyperandrogenism, and polycystic ovaries: a report of 3 cases.

BACKGROUND: Reproductive endocrine disorders characterized by menstrual disorders, polycystic ovaries, and hyperandrogenism seem to be common among women treated with sodium valproate for epilepsy. OBJECTIVE: To describe the development of valproate-related reproductive endocrine disorders in women with epilepsy. DESIGN: Case report. PATIENTS: Three patients developed a reproductive endocrine disorder during treatment with valproate. It was characterized by hyperandrogenism and polycystic ovaries in all cases, and it was associated with weight gain and menstrual disorders in 2 of the 3 women. RESULTS: Replacing valproate with lamotrigine resulted in a decrease in serum testosterone concentrations in all 3 women. The polycystic changes disappeared from the ovaries in 2 of the women after valproate therapy was discontinued, and the 2 women who had gained weight and developed amenorrhea while being treated with valproate lost weight and resumed menstruating after the change in medication. CONCLUSIONS: The 3 cases presented here illustrate the development of reproductive endocrine disorders after the initiation of valproate therapy in women with epilepsy. The disorders were characterized by hyperandrogenism and polycystic ovaries in all cases, and were associated with weight gain and menstrual disorders in 2 of the 3 women. An evaluation of ovarian structure and function should be considered in women of reproductive age being treated with valproate for epilepsy, especially if they develop menstrual cycle disturbances during treatment.

Adolescent↗
PubMedDate not supplied

Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics.

The reproductive effects of metabolic disorders in women can be divided into four categories. The first of these is infertility. Galactosemia with its complication of ovarian failure is the disorder in this category. This complication may be prenatal in origin but whether this is so and its cause are unknown. The second category includes pregnancy effects of maternal metabolic disorders. The urea cycle disorder ornithine transcarbamylase (OTC) deficiency, maternal maple syrup urine disease and maternal homocystinuria are in this category. In the first two disorders, postpartum life-threatening illness due to metabolic crisis has occurred. Maternal homocystinuria is associated with a high risk for postpartum thromboembolic complications. The third category is the pregnancy effect of a fetal metabolic disorder. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) have been complicated by the life-threatening (HELLP) syndrome during the third trimester. Rapid recovery of the mothers followed delivery, on occasion by emergency cesarean section. The fourth category is the fetal effects (teratogenicity) from a maternal metabolic disorder. The best-known example of this is maternal phenylketonuria (PKU), which produces microcephaly, mental retardation, congenital heart disease and intrauterine growth retardation. Treatment with a low phenylalanine diet begun before conception or no later than the earliest weeks of the first trimester markedly reduces the risk to the fetus and can result in normal offspring. Other examples of teratogenicity may include maternal homocystinuria and maternal hypothyroidism.

Female↗
PubMed2002

Work-related reproductive, musculoskeletal and mental disorders among working women--history, current issues and future research directions.

According to the recent changes of working environments and socio-economical conditions, the proportion of working women are increasing in Japan. Characteristics of occupational workload and stress of Japanese working women are consistent with those in many industrialized countries except man-dominant culture. In this review we describe the history, current issues, and future research directions on occupational health of working women, especially focused on reproductive health, work-related musculo-skeletal disorders (WMSDs), and mental disorders. In the reproductive health survey, traditionally main concern was about pregnancy outcomes, then fecundity studies, such as time to pregnancy, became topics recently. Future research will be shifted to outcomes not only during pregnancy but also disorders of hormonal balance and climacterium or health conditions after menopause. WMSDs are reviewed on mainly gender difference and its causative factors. Historically, mental health of working women in Japan has focused on the job stress of nurses. We compare results with a lot of recent researches in Europe and U.S.A., where interaction between occupational stress and family roles were studied. It is not easy to predict the prospective status of female workers in Japan, but social, workplace and familial supports will enhance their health promotion.

Female↗
PubMed2004

Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility.

The observed to expected episodes of care experience of 652 employees at a fluorochemical (perfluorooctanesulfonyl fluoride) production facility was compared with 659 film plant (nonfluorochemical) employees at the same site (Decatur, AL). Episodes of care were defined by a hierarchical analysis of health claims data from 1993 through 1998. The age- and sex-adjusted expected number of episodes of care was calculated from the company's U.S. manufacturing workforce. For a priori interests, the observed to expected episodes of care ratios were comparable for fluorochemical and film plant employees for liver tumors or diseases, bladder cancer, thyroid and lipid metabolism disorders, and reproductive, pregnancy, and perinatal disorders and higher for biliary tract disorders and cystitis recurrence. Non-a priori associations among the fluorochemical plant workers included benign colon polyps, malignant colorectal tumors, and malignant melanoma.

Adult↗
PubMed2005

Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy.

It is well known that epilepsy, antiepileptic drugs (AEDs), and the reproductive system have complex interactions. Fertility is lower in both men and women with epilepsy than in the general population. Moreover, reproductive endocrine disorders are more common among patients with epilepsy than among the population in general. These disorders have been attributed both to epilepsy itself and to use of AEDs. The use of the liver enzyme-inducing AEDs phenobarbital, phenytoin and carbamazepine increases serum sex hormone-binding globulin (SHBG) concentrations in both men and women with epilepsy. Over time, the increase in serum SHBG levels leads to diminished bioactivity of testosterone and estradiol, which may result in diminished potency in men and menstrual disorders in some women, and thus to reduced fertility. Liver enzyme-inducing AEDs also reduce the efficacy of oral contraceptives. Valproic acid medication may have effects on serum androgen concentrations and it reduces serum follicle stimulating hormone levels in men with epilepsy. However, the clinical significance of valproic acid-related reproductive endocrine changes in men is unknown. On the other hand, in women, use of valproic acid appears to be associated with a frequent occurrence of reproductive endocrine disorders characterised by polycystic changes in the ovaries, high serum testosterone concentrations (hyperandrogenism) and menstrual disorders. These disorders are especially common among women who have gained weight during valproic acid treatment. There are some discrepancies regarding the reported occurrence of reproductive endocrine disorders in women taking valproic acid for epilepsy. However, most studies also including patients receiving valproic acid for other reasons than epilepsy, and studies in different non-epileptic animal models, have shown an association between valproic acid medication and hyperandrogenism and related reproductive endocrine disorders. From a practical point of view, the length of the menstrual cycles and bodyweight should be monitored in women with epilepsy after commencement of treatment with valproic acid. A serum testosterone assay is helpful in following the possible biochemical endocrine changes. Ultrasonography of the ovaries (preferably transvaginal) is indicated if clinical assessment and serum testosterone measurement imply that there is a clinically significant valproic acid-related reproductive endocrine problem. That would be the case if the menstrual cycles were irregular or prolonged (usually >35 days) and serum testosterone levels elevated, especially with associated weight gain. The endocrine effects of the new AEDs have not been widely studied. However, it seems they may offer an alternative if reproductive endocrine problems emerge during treatment with the older AEDs.

Anticonvulsants↗
PubMed2005

Genetic manipulations to study reproduction.

Fertility disorders affect approximately 15% of individuals worldwide. With the imminent completion of the human and mouse genome sequence, it will be more feasible to identify the relevant genes underlying many fertility disorders. Already, the mouse has been utilized extensively as a genetic tool for the dissection of gene function, often providing significant insights into the relationship between gene and disease. In fact, there are over 200 mouse models that display reproductive defects. However, the available mouse mutant resources provide functional information for a mere 10% of the total number of genes in the mouse or human genomes at best. The improvement of available genome annotations together with more powerful techniques to manipulate the mouse genome provide substantial improvements in our ability to identify genes involved in reproduction, and in the future will likely benefit patients with fertility problems.

Animals↗
PubMed2005

Sexual hormones and epilepsy: threat and opportunities.

PURPOSE OF REVIEW: This article reviews recent developments in our knowledge of the reciprocal interactions between epilepsy and sex hormones and how these interactions may play a role in the pathophysiology and treatment of both. RECENT FINDINGS: Community studies confirm that menstrual disorders are overrepresented among women with epilepsy, especially among women with high seizure frequency and in those on valproate or polytherapy. Reproductive function is not affected in women with epilepsy who discontinued antiepileptic drug therapy during pubertal maturation. While valproate has been implicated as having particularly notable disruptive effects on reproductive function in women with epilepsy (polycystic ovaries and hyperandrogenemia), this was not evident in non-epileptic primates. The role of epilepsy itself is evident from a study that showed that the laterality of unilateral temporolimbic discharges is associated with predictable directional changes in hormonal secretion at all levels of the reproductive neuroendocrine axis. Epilepsy in men is associated with reduced levels of sexual function, bioactive testosterone and sperm. Various antiepileptic drugs may differ in this regard. SUMMARY: Epilepsy and antiepileptic drugs can alter sex hormone levels to promote the development of reproductive endocrine disorders in both women and men. Reproductive endocrine disorders may adversely affect both reproductive function and seizure control. Treatment of epilepsy and selection of antiepileptic drugs may be important to reproductive health in women and men with epilepsy. Sex steroids and their metabolites may also provide treatment for seizures.

Epilepsy↗
PubMed2005

Assisted reproductive therapies and imprinting disorders--a preliminary British survey.

BACKGROUND: Recent reports have suggested a higher risk of Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) after assisted reproductive technologies (ARTs), but it is unclear whether this might also apply to other disorders of genomic imprinting. METHODS: We contacted families of children with BWS, AS, Prader-Willi syndrome (PWS) and transient neonatal diabetes mellitus (TNDM) to determine use of ART. RESULTS: A statistically significant increased frequency of ART in children with BWS was confirmed [2.9%, 95% confidence interval (CI) 1.4-6.3% vs 0.8% expected] but there was no significant association with PWS or TNDM. Consideration of the molecular subgroup of BWS and AS suggested the feasibility of association with ART. CONCLUSIONS: These differences may relate to variations in (i) the molecular mechanisms for disordered imprinting in the different disorders and (ii) the susceptibility of specific imprinting control regions to ART-associated methylation alterations (epimutations).

Angelman Syndrome↗
PubMed2006

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.

Adolescent↗
PubMed2002

The effect of reproductive compensation on recessive disorders within consanguineous human populations.

We investigate the effects of consanguinity and population substructure on genetic health using the UK Asian population as an example. We review and expand upon previous treatments dealing with the deleterious effects of consanguinity on recessive disorders and consider how other factors, such as population substructure, may be of equal importance. For illustration, we quantify the relative risks of recessive lethal disorders by presenting some simple calculations that demonstrate the effect 'reproductive compensation' has on the maintenance of recessive alleles. The results show how reproductive compensation can effectively counteract the purging of deleterious alleles within consanguineous populations. Whereas inbreeding does not elevate the equilibrium frequency of affected individuals, reproductive compensation does. We suggest this effect must be built into interpretations of the incidence of genetic disease within populations such as the UK Asians. Information of this nature will benefit health care workers who inform such communities.

Alleles↗
PubMed2002

Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management.

BACKGROUND: Epilepsy is commonly associated with reproductive endocrine disorders. These include polycystic ovary syndrome (PCOS), isolated components of this syndrome such as polycystic ovaries, hyperandrogenaemia, hypothalamic amenorrhoea, and functional hyperprolactinaemia. OBJECTIVE: To summarise the currently known relations between epilepsy and reproductive endocrine disorders. METHODS: A review of clinical experience and published reports. RESULTS: The most likely explanations for endocrine disorders related to epilepsy or antiepileptic drugs are: (1) a direct influence of the epileptogenic lesion, epilepsy, or antiepileptic drugs on the endocrine control centres in the brain; (2) the effects of antiepileptic drugs on peripheral endocrine glands; (3) the effects of antiepileptic drugs on the metabolism of hormones and binding proteins; and (4) secondary endocrine complications of antiepileptic drug related weight changes or changes of insulin sensitivity. Regular monitoring of reproductive function at visits is recommended, including questioning about menstrual disorders, fertility, weight, hirsutism, and galactorrhoea. Particular attention should be paid to patients on valproate and obese patients or those experiencing significant weight gain. Single abnormal laboratory or imaging findings without symptoms may not constitute a clinically relevant endocrine disorder. However, patients with these kinds of abnormalities should be monitored to detect the possible development of a symptomatic disorder associated with, for example, menstrual disorders or fertility problems. CONCLUSIONS: If a reproductive endocrine disorder is found, antiepileptic drug treatment should be reviewed to ensure that it is correct for the particular seizure type and that it is not contributing to the endocrine problem. The possible benefits of a change in treatment must be balanced against seizure control and the cumulative side effect of alternative agents.

Anticonvulsants↗
PubMedDate not supplied

Psychoneuroendocrine aspects of temporolimbic epilepsy. Part II: Epilepsy and reproductive steroids.

Reproductive dysfunction is unusually common among men and women with epilepsy. Reproductive endocrine disorders are also common and may be causal. The association between particular reproductive endocrine disorders and the laterality and focality of epileptiform discharges suggests an etiologic role for epilepsy. Gonadal steroids are neuroactive and influence seizure occurrence: estrogen is epileptogenic whereas progesterone has antiseizure effects. Fluctuations in the absolute and relative serum levels of these hormones may play a critical role in establishing three distinct patterns of catamenial epilepsy: 1) perimenstrual and 2) preovulatory in women with ovulatory cycles, and 3) entire luteal phase of the cycle in women with anovulatory cycles. Treatment with progesterone reduces seizure frequency by more than half. In men, testosterone effects may depend on the relative concentrations of two major testosterone metabolites that exert opposing influences on neuronal excitability: estrogen potentiates whereas dihydrotestosterone inhibits NMDA-mediated conductance. Combined therapy using an aromatase inhibitor along with testosterone improves sexual function and may reduce seizures in men with epilepsy.

Animals↗
PubMedDate not supplied

Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men.

BACKGROUND: The Men in Australia Telephone Survey (MATeS) describes the prevalence of self-reported reproductive health disorders as well as related concerns and health behaviours among middle-aged and older Australian men. METHODS: A representative sample population (n=5990) of Australian men (>or=40 years) was obtained by contacting a random selection of households with unbiased sampling, stratified by age and state. A 20-min computer-assisted telephone interview was done to assess reproductive health and related knowledge and beliefs, sociodemographic factors, general health, and lifestyle factors. FINDINGS: A response rate of 78% (5990/7636) was achieved. 34% (1627/4737) of men surveyed reported one or more reproductive health disorder, all of which were most common in the oldest age group. Age-standardised prevalence of significant lower urinary tract symptoms was 16%, erectile dysfunction was 21%, and prostate disease was 14%. About 50% of participants reported having had a prostate cancer test whereas only 30% (300/1012) of men with erectile dysfunction sought medical help. Willingness to seek medical help for erectile dysfunction was related to age and ethnic origin. Although men aged 40-69 years expressed a moderate or high level of concern about prostate cancer and loss of erectile function, concern about reproductive health was less in the oldest age group (>or=70 years). INTERPRETATION: The high prevalence of reproductive health disorders and associated concerns in middle-aged and older Australian men draws attention to the need to develop appropriate services and education strategies specifically directed to improving reproductive health in these men.

Adult↗
PubMed1994

Altered pulsatile secretion of luteinizing hormone in women with epilepsy.

Menstrual disorders and infertility are common among women with epilepsy of temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause. Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic hypogonadism, HH), in particular, are significantly overrepresented and attributable to hypothalamic dysfunction. We therefore compared the hypothalamic function of 14 women with clinically and electrographically documented TLE with that of eight age-matched normal controls by determining the interictal pulse frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse frequency values were significantly more variable (p < 0.05) and lower (p < 0.05) among women with TLE than among controls. Women with left temporal EEG foci showed a trend toward higher pulse frequencies compared to women with right foci (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the three with PCO had left-sided foci and average LH pulse frequency two times higher than that of the two women with HH, who had right-sided foci. Eight reproductively normal, medically treated women with TLE had significantly lower LH pulse frequencies than did the one reproductively normal, untreated woman with TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest that LH pulse frequencies in women with TLE may be influenced by the laterality of the epileptic focus, the reproductive endocrine status, and the use of antiseizure medications.

Adult↗
PubMedDate not supplied

Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology.

Recent studies suggest a possible link between human assisted reproductive technology and genomic imprinting disorders. Assisted reproductive technology includes the isolation, handling and culture of gametes and early embryos at times when imprinted genes are likely to be particularly vulnerable to external influences. Evidence of sex-specific differences in imprint acquisition suggests that male and female germ cells may be susceptible to perturbations in imprinted genes at specific prenatal and postnatal stages. Imprints acquired first during gametogenesis must be maintained during preimplantation development when reprogramming of the overall genome occurs. In this review, we will discuss both new developments in our understanding of genomic imprinting including the mechanisms and timing of imprint erasure, acquisition and maintenance during germ cell development and early embryogenesis as well as the implications of this research for future epigenetic studies in reproduction and assisted reproductive technology.

Angelman Syndrome↗
PubMed2002

GnRH-immunoreactive fiber changes with unilateral amygdala-kindled seizures.

PURPOSE: To assess whether unilateral amygdala seizures are associated with a change in the number and lateral distribution of gonadotropin releasing hormone (GnRH)-staining fibers in the ventromedial hypothalamus of female rats. METHODS: The study compared three groups of female rats: (1) amygdala seizures induced by focal injection of kainic acid (KA); (2) saline injected controls; and (3) nai;ve controls. The animals were sacrificed at 4 weeks in the diestrus phase. GnRH fibers were counted in the ventromedial hypothalamus and compared among groups. RESULTS: GnRH fiber counts were significantly lower in KA than saline and nai;ve animals ipsilaterally but not contralaterally. CONCLUSIONS: This finding may support a potential mechanism by which (1) temporolimbic epilepsy may promote the development of reproductive endocrine disorders and (2) the laterality of the epilepsy may influence the particular nature of the reproductive endocrine disorder.

Amygdala↗