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Clomiphene therapy in epileptic women with menstrual disorders.

We studied the effects of clomiphene therapy on seizure frequency in 12 women who had clinical and EEG features of complex partial seizures as well as menstrual disorders with reproductive endocrine abnormalities. Ten of the 12 women improved (p less than 0.05); all ten developed normal cycles. The two women who did not improve continued to have irregular prolonged cycles. Average monthly seizure frequency for the entire group declined by 87% (p less than 0.01). Both complex partial and secondary generalized seizures decreased. During the investigation, one unwanted pregnancy occurred, two women developed severe abdominal pain with ultrasound-documented ovarian cysts, and three experienced breast tenderness and pelvic cramps.

Adult↗

Management issues for women with epilepsy: a review of the literature.

OBJECTIVE: A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter. BACKGROUND: Epilepsy is a common neurologic condition with gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life. METHODS: An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding. RESULTS: Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation. CONCLUSIONS: WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.

Anticonvulsants↗

Serum dioxin, testosterone, and subsequent risk of benign prostatic hyperplasia: a prospective cohort study of Air Force veterans.

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962-1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73-0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.

Dioxins↗

Hypogonadism, galactorrhoea and hyper-prolactinaemia: Evaluation of pituitary gonadotrophins reserve before and under bromocriptine.

Twenty patients with hypogonadism (19 women with amenorrhoea and 1 man with impotence and infertility), galactorrhoea and hyper-prolactinaemia (range: 36 to 344 ng/ml) were studied. The radiological study of the sella turcica, including in all cases hypocycloidal tomograms, allowed classification of the patients into 3 groups: group I (n = 4) had a grossly enlarged sella turcica, group II (n = 12) had localized alterations indicating the probable existence of a prolactin-secreting microadenoma ("microdeformation") while group III patients presented no radiological abnormality. Before treatment, all the patients were submitted to a complete evaluation of the function of their anterior pituitary, including the LH and FSH responses to iv administration of Gn-RH. All the group I patients had low basal LH levels and a blunted response to Gn-RH. The basal LH and in response to Gn-RH were normal in most of the group II patients and in all of the group III patients. An exaggerated FSH response to Gn-RH was observed in 6/12 patients with microdeformation (group II) but not in groups I and III patients. A low LH and a blunted LH response to Gn-RH is highly suggestive of the existence of a pituitary prolactin-secreting adenoma in case of amenorrhoea and hyper-prolactinaemia patients; a normal response does not however rule out such a diagnosis. The reasons for a exaggerated FSH response to Gn-RH in patients with suspected prolactin-secreting microadenoma remain to be investigated though this pattern can also occur in other cases of amenorrhoea. Hence the Gn-RH test might contribute to the assessment of the hypothalamo-pituitary axis of patients with hyper-prolactinaemia. Six patients treated for 4 months with bromocriptine (CB-154) were submitted to re-evaluation of their pituitary gonadotrophins reserve. All the women experienced restoration of menses with 39 days of treatment and the male patient regained potency. It was observed that bromocriptine treatment and subsequent normalized prolactin levels in the 4 group II women tested were associated with normalization of their previously exaggerated FSH response to Gn-RH; LH responses were also diminished in these cases. These data are compatible with the hypothesis that hyper-prolactinaemia per se could interfere with the endogenous secretion of Gn-RH at the hypothalamic level. In one patient with grossly enlarged sella turcica and a previous lack of an LH and FSH response to Gn-RH, bromocriptine treatment restored a normal gonadotrophins response, confirming that, in this case, the alteration of this response was indeed due to a prolonged lack of endogenous Gn-RH secretion.

Adolescent↗

Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome.

The amount of research into endocrine disruption has exploded over the past decade and a re-evaluation of the state of research in this area is timely. There are debates about whether human male reproductive health is really declining and whether endocrine disrupting chemicals play any role in the perceived decline. Most data currently conclude that there are wide geographical variations in semen quality and in the incidence of testicular cancer, cryptorchidism and hypospadias. This review aims to give a brief overview of the issues surrounding the perceived decline in human male reproductive health and the importance of the hormonal environment for the development of the testis and reproductive tract. The consequences for the male reproductive tract of abnormal androgen levels or action are discussed with reference to environmental anti-androgenic compounds. The in vivo data on several anti-androgenic compounds that have been administered to pregnant rodents during the period of male reproductive tract development are assessed with attention to the effects on the male offspring. Finally, the data on in utero phthalate administration are discussed in detail to illustrate the similarities between the effects of some phthalate esters and the human male reproductive tract disorders which comprise testicular dysgenesis syndrome (TDS).

Androgen Antagonists↗

Exogenous interferon-gamma alters murine inner cell mass and trophoblast development. Effect on the expression of ErbB1, ErbB4 and heparan sulfate proteoglycan (perlecan).

Implantation is a crucial event in human pregnancy. The participation of cytokines in the implantation process has been widely documented, although the role of many of these molecules is still a matter of controversy. In a previous report from our laboratory, we demonstrated that addition of interferon-gamma to the culture medium produces deleterious effects on mouse embryo development. In this study we investigated the effect of this cytokine on outgrowing embryo morphology and on the expression of epidermal growth factor receptors (ErbBs) and heparan sulfate proteoglycan (perlecan) in mouse embryos cultured in vitro. Morphological assessment of inner cell mass and trophoblast development was carried on in-situ fixed and stained outgrowths. Localization of ErbB1, ErbB4 and perlecan on pre- and peri-implantation embryos was investigated by immunocytochemistry. Addition of interferon-gamma produced a deleterious effect on both inner cell mass and trophoblast morphology. Immunostaining demonstrated that ErbB1, ErbB4 and perlecan are present on pre-implantation embryos and blastocysts; interferon-gamma altered the expression of ErbB4 and Perlecan at the blastocyst stage. We propose that the effects produced by this cytokine could be related to the altered acquisition of adhesion competence and low implantation rates observed in certain reproductive immunological disorders.

Animals↗

[Factors associated with minor psychiatric disorders among women selected from a healthcare center in Rio de Janeiro, Brazil].

The aim was to investigate factors potentially associated with minor psychiatric disorders, including maternal nutritional status variables. A cohort was studied with 479 women 15-45 years of age. The reduced General Health Questionnaire (GHQ-12 items) was applied at nine months post-partum with the 312 women who had completed follow-up. Minor psychiatric disorder was defined as a GHQ score of > or = 4 points and was treated as the response variable. Statistical analysis used hierarchical multivariate logistic regression models. The prevalence of minor psychiatric morbidity was 54.2% (95%CI: 48.6-59.7). According to the final model, the following variables remained statistically associated with minor psychiatric morbidity: level 1: total family income (1st quartile: OR = 2.71, 95%CI: 1.42-5.19; 2nd quartile: OR = 2.13; 95%CI: 1.13-4.04); level 3: body fat > or = 30% (OR = 1.66; 95%CI: 1.03-2.65). In conclusion, low income and obesity were the only factors potentially associated with minor psychiatric disorders, even after adjusting for confounding variables, while there are few studies relating maternal nutritional status and minor psychiatric morbidity.

Adolescent↗

[Syphilis positivity in puerperal women: still a challenge in Brazil].

OBJECTIVE: To investigate the factors associated with positive syphilis serology results in puerperal women who were receiving care at 24 health centers accredited by Brazil's National Program on Sexually Transmitted Diseases and AIDS. METHODS: This cross-sectional study included a probabilistic random sample of 3047 puerperal women. The eligibility criterion was being admitted for delivery or curettage in the selected centers. After an interview to collect demographic and clinical information, a blood sample was taken and then examined with the Venereal Disease Research Laboratory (VDRL) slide test. With positive VDRL results, the fluorescent treponemal antibody-absorption test (FTA-Abs) was used for confirmation. The event considered for analysis was positivity on the VDRL test, with confirmation by the FTA-Abs. For the statistical analysis, odds ratios and 95% confidence intervals were calculated. The model fit was assessed using the Hosmer-Lemeshow test. RESULTS: The prevalence of syphilis among the women studied was 1.7%. Multivariate analysis showed that increased risk for positive VDRL and FTA-Abs results was associated with the following characteristics: family income below one minimum wage, age < 17 years at first sexual intercourse, age < or = 14 years at first pregnancy, history of syphilis or of other sexually transmitted diseases prior to the current pregnancy, treatment for syphilis during the current pregnancy, partner having been tested for syphilis, having a positive HIV test result or having no HIV test result on record, previous preterm delivery, and stillbirth as an outcome of pregnancy. Only 43% of the women had had six or more prenatal visits, and only 3% had had one VDRL test during the first trimester of pregnancy and another VDRL test during the third trimester, as is recommended by Brazil's national Ministry of Health. CONCLUSIONS: This study shows that the problem of congenital syphilis is far from being solved in Brazil. It is necessary to provide adolescents with family planning services as well as guidance on sexual issues, to improve prenatal follow-up, and to research the history of sexually transmitted diseases in both the pregnant woman and her sexual partner.

Adolescent↗

The orphan Rev-erb nuclear receptors: a link between metabolism, circadian rhythm and inflammation?

Nuclear hormone receptors (NRs) function as ligand dependent DNA binding proteins that translate physiological/nutritional signals into gene regulation. Dysfunctional NR signaling leads to many disorders in reproduction, inflammation, and metabolism. The opportunity to identify novel regulatory pathways in the context of human health and disease drives the challenge to unravel the biological function of the "orphan nuclear hormone receptors". For example, the Rev-erb (NR1D) subgroup (Rev-erbalpha/NR1D1 and Rev-erbbeta/NR1D2) of orphan NRs are transcriptional silencers and negative regulators of RORalpha mediated trans-activation. The NR1D subgroup is highly enriched in peripheral tissues with onerous energy demands including skeletal muscle, brown and white adipose, brain, liver and kidney. This alludes to the involvement of this subgroup in metabolism. In this context, Rev-erbalpha-/- mice have a dyslipidemic phenotype. Recent studies in vascular smooth and skeletal muscle cells also suggest that the NR1D subgroup modulates inflammation by regulating IkappaBalpha/NFkappaB dependent gene expression. Rev-erbalpha has been identified as a critical regulator (and target) of circadian rhythm, a factor in blood pressure control and inflammation. Finally, two recent reports have demonstrated: (i) lithium mediated regulation of Rev-erbalpha stability and (ii) E75 (the Drosophila orthologue of human Rev-erbalpha) is tightly bound by heme, and functions as a "gas sensor" through interaction with CO/NO and interferes with the repression of DHR3 (the Drosophila orthologue of human RORalpha). In conclusion, the role of these receptors at the cross-roads of metabolism, inflammation, and circadian cycling underscores the importance of understanding the organ-specific function of the NR1D subgroup in homeostasis.

Journal Article↗

Reduced fertility and neuroendocrine dysfunction in women with epilepsy.

A reduction of fertility in women with epilepsy has been reported since 1950 and is confirmed in recent epidemiological studies. This phenomenon has usually been attributed to the increase of medical and socioeconomic problems in these patients or to hyposexuality, which has been consistently observed in epileptic subjects. Recently, a higher occurrence of reproductive endocrine diseases has been reported in epileptic women and proposed as an important cause of reduced fertility. In particular, polycystic ovary syndrome and hypothalamic ovarian failure have been reported in epileptic women with increased frequency compared to the general population. Moreover, an abnormal pattern of luteinizing hormone (LH) pulsatility has been observed in normally cycling, drug-free epileptic women. We suggest that epilepsy may interfere with the functional activity of the gonadotropin releasing hormone (GnRH) pulse generator. It is possible that paroxysmal discharges spreading within the hypothalamus might affect the regularity of the GnRH pulse generator; alternatively, a neurotransmitter dysfunction might at the same time be responsible both for the lowering of the seizure threshold and for the dysfunction of GnRH secretion. The consequent alteration of LH pulsatility might in the long run, under the effect of additional factors, give rise to a clinical reproductive endocrine disorder.

Epilepsy↗

Effects of prepartum milking on milk production and health performance.

A field study using seven Holstein herds was conducted to determine effects of prepartum milking on milk production, health disorders, and reproductive performance. In each herd, 80 cows (30% first lactation cows) were assigned 1 mo prior to expected calving date to one of two treatments: postpartum or prepartum milking. The group milked prepartum was machine-milked twice daily at regular milking intervals beginning 14 d prior to date of expected calving. The group milked postpartum was milked for the first time after calving. The day prior to calving, 36, 33, and 31% of the cows milked prepartum produced less than 4.5 kg, 4.5 to 9 kg, and greater than 9 kg of milk, respectively. No relationship existed between days milked prepartum and prepartum milk yield. Lactation milk yield and persistency were not affected by prepartum milking. Prepartum milking reduced incidence of milk fever and mastitis during the 1st mo after parturition. Treatment was not a significant source of variation for reproductive performance or body condition; however, culling was higher for cows milked postpartum. Results indicate no adverse effects on cow performance due to prepartum milking nor increase in lactation milk yield.

Animals↗

[[The duration of postpartum amenorrhea in a Sundanese village]].

"The duration of postpartum amenorrhea of women in a Sundanese agricultural village [in Indonesia] whose last pregnancy resulted in live birth in the past six years was studied. Data were collected from 197 women from September through November 1983....[The] results suggest that the duration of postpartum amenorrhea of women in a Sundanese agricultural village although relatively long, has recently become shorter." (SUMMARY IN ENG)

Amenorrhea↗

On a modification of life table technique for analysis of birth interval data and its application.

"This paper presents some modifications [of] the usual life table technique to analyse the data on the time of first birth and inter live birth intervals which are compiled from the birth histories of females, of varying marital durations, enumerated in a retrospective survey." The fact that a female may not be exposed to the risk of conception following childbirth or marriage, because of postpartum amenorrhea or of customs involving visits to parents, is taken into account. A method to obtain maximum likelihood estimates of the conditional risk of conception is given, and an analysis of birth intervals is presented using this technique and data for India from the Rural Development and Population Growth--A Sample Survey 1978.

Amenorrhea↗