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Controversial issues of dietary fat and experimental mammary carcinogenesis.

Epidemiological evidence from different countries worldwide has suggested a positive association between the availability of fat in the diet and variations in breast cancer mortality rate. A voluminous amount of information is also available in the literature linking increased fat consumption, particularly polyunsaturated fat, and stimulation of mammary tumorigenesis in animal models. In the past few years, our laboratory has been studying the impact of several confounding factors that could modulate the enhancing effect of fat on neoplastic development of the mammary gland in female rats which are treated with a carcinogen. It is our conclusion that fat promotes mammary carcinogenesis only under a very stringent set of conditions which might not be duplicated in the arena of fat intake and human breast cancer risk. Previous studies on fat and mammary cancer in experimental models have used young virgin rats which are given a dose of carcinogen at a particular age. The question arises as to whether the promoting effect of fat might be a consequence of the characteristics of the model. We have supportive evidence showing that the following criteria must be satisfied in order for fat enhancement of mammary carcinogenesis to be manifested: (a) carcinogen administered at a time when the mammary gland is exquisitely susceptible to tumor induction, (b) animals maintained on a semipurified diet, (c) ad libitum feeding necessary, and (d) unusually high requirement of linoleic acid for tumor development. On the other hand, the stimulatory effect of fat is attenuated or sometimes even negated by (a) feeding of a natural ingredient diet, (b) submaximal calorie intake, and (c) previous history of pregnancy and lactation. Given the spectrum of confounders that are inherent in epidemiological studies linking fat intake and breast cancer, including differences in lifestyle, reproductive history, eating habits, as well as complexity of the total diet, our findings suggest that there may be a need to reevaluate the validity of extrapolating animal data that are obtained under a highly defined set of conditions to the etiological significance of dietary fat in human breast cancer.

Animals↗

Evidence of improved pregnancy outcome with diethylstilbestrol (DES) treatment of women with previous pregnancy failures: a retrospective analysis.

In a longitudinal study of 2378 pregnancies, diethylstilbestrol (DES) therapy was associated with an increased live-birth rate in patients with a history of prior pregnancy wastage. The data were analyzed statistically by comparing the rates of success with and without DES treatment in pregnancies grouped according to similar reproductive histories. The effect of DES on the outcome of pregnancy has not been assessed previously in this manner.

Abortion, Threatened↗

Clinical approach to infertility in the cycling bitch.

The majority of "infertile" bitches presented to the practitioner are victims of mismanagement. Careful evaluation of reproductive history, physical examination, and vaginal cytologic evaluation permit conception in these patients. Measurement of serum progesterone levels can help establish occurrence and timing of ovulation. Diagnosing true reproductive problems may require a minimum data base, guarded cultures, vaginoscopy, vaginography, ultrasound, and ultimately laparotomy for uterine biopsy and culture. The majority of these diagnostic procedures are readily available for the interested practitioner.

Animals↗

Abortion and subsequent substance abuse.

A statistical association between a history of substance abuse and a history of abortion has been identified in several studies, but this association has not yet been thoroughly analyzed. This study draws on a subset of data from a reproductive history survey that included a nonparametric self-assessment of past substance abuse distributed to a random sample of American women. Analysis of this substance abuse variable showed that a report of substance abuse following a first pregnancy was associated significantly with (a) abortion for all women, (b) abortion for adolescents, and (c) abortion for women over 19 years of age. Women who aborted a first pregnancy were five times more likely to report subsequent substance abuse than women who carried to term, and they were four times more likely to report substance abuse compared to those who suffered a natural loss of their first pregnancy (i.e., due to miscarriage, ectopic pregnancy, or stillbirth). Women with a history of abortion or a history of substance abuse were significantly more likely to feel discomfort in responding to the survey. The findings of this study have important implications for the design of future studies examining substance abuse, adolescents, and women. These findings may also have clinical and counseling implications.

Abortion, Induced↗

Reproduction in high altitude Aymara: physiological stress and fertility planning?

Reproductive characteristics at high altitude are described based on the reproductive histories of 720 Aymara women, collected in 1998 and 1999 in a group of twelve peasant communities at a mean altitude of 4000 m in the Bolivian Altiplano. The reproductive pattern is shaped by a late onset of childbearing, associated with a rather short reproductive span and large birth intervals. Environmental conditions could explain the particularly late age at menarche of rural girls compared with their urban counterparts, whereas the age at first birth is likely to be under cultural control. The short reproductive span appears to result from a large mean interval between last birth and menopause, which is essentially determined by cultural decisions. The birth intervals, which are longer than in many traditional societies, could be the result of a slower restoration of postpartum fecundability induced by the hard way of life inherent in the Altiplano (including poor sanitary and nutritional conditions and high workload), perhaps aggravated by hypoxia. However, a secular trend in fertility is perceptible, towards earlier menarche, earlier age at first birth, increasing reproductive span and a slight increase in live births and surviving offspring, which is probably the result of a slow improvement in living conditions. The existence of birth control on the one hand, and a total fertility rate averaging six live births among the couples who do not practise contraception on the other, are other arguments against the hypothesis of a low natural fecundity in these Aymara groups.

Adolescent↗

Determinants of utilization of Tay-Sachs screening.

OBJECTIVE: To identify the characteristics of patients associated with optimal utilization of Tay-Sachs screening. METHODS: Medical records of patients undergoing amniocentesis for genetic diagnosis were reviewed. Three hundred twenty-nine of 537 charts evaluated were from individuals at risk for Tay-Sachs heterozygosity. Among these, 213 couples had previously been screened for Tay-Sachs. In 116 couples, neither member of the couple had been screened before amniocentesis. A concurrent reference group consisted of 208 couples without an indication for Tay-Sachs screening. Patient characteristics, including ethnicity, genetic screening history, parental ages, and pregnancy history, were reviewed for each group. Analysis of variance and likelihood chi 2 test were used for statistical analysis. RESULTS: There were no significant differences in maternal age or reproductive history among the groups. The most common indication for amniocentesis was advanced maternal age for all three groups. However, the previously screened group was more than twice as likely to self-refer because of a positive family history or patient anxiety than was the unscreened group (P = .006). Conversely, the unscreened group was more than twice as likely as screened couples to be referred because of a positive high or positive low maternal serum alpha-fetoprotein level (P = .002). CONCLUSION: Despite 2 decades of professional and lay education, many couples are unaware of their individual risk for Tay-Sachs heterozygosity. Additional education, most likely at the professional level, is needed to maximize informed participation.

Fathers↗

History of childbearing and colorectal cancer risk in women aged less than 60: an analysis of Swedish routine registry data 1960-1984.

Data from a computerised linkage between the Swedish Cancer Registry and the Fertility Registry were used to study the influence of reproductive history on the risk of colorectal cancer in women aged less than 60, in the period 1960 to 1984. A "nested" case-control design was used with 1,415 colon cancer cases and 733 rectal cancer cases, and 7,073 and 3,665 age-matched controls, respectively. Conditional logistic regression was employed to study the independent effects of parity, age at first birth and years since last birth on the risk of colorectal cancer. High parity was associated with reduced risk in women older then 50 years at diagnosis, both for the colon as a whole and for colon subsites. Women having had 5 children or more had an odds of colon cancer of 0.44 (95% confidence interval 0.24-0.82) relative to that of nulliparous woman. Contrary to the hypothesis advanced by McMichael and Potter (J. Nat. Cancer Inst., 75, 185-191 [1985]), which predicted a strong protective effect of parity in the proximal compared to the distal colon, we found the reverse. Increasing years since last birth seemed to be associated with a reduced risk of rectal cancer. A significant positive trend with increasing age at first birth was suggested with respect to distal colon cancer and rectal cancer risk. The mutually adjusted effects of the reproductive variables under study were similar to the unadjusted effects. Our data suggest that increasing parity is associated with a decline in risk of colon cancer but not rectal cancer, although the association with colon cancer is restricted to women aged 50 or more. The effects of age at first birth and years since last birth are not consistent or pronounced.

Adult↗

Arab Americans, African Americans, and infertility: barriers to reproduction and medical care.

OBJECTIVE: To compare barriers to infertility care among African Americans and Arab Americans. DESIGN: Qualitative study using semi-structured reproductive histories and open-ended ethnographic interviews. SETTING: Infertile volunteers in a private IVF clinic in Dearborn, Michigan, an Arab American ethnic enclave community in metropolitan Detroit. PATIENT(S): Arab American men presenting for infertility diagnosis and treatment, including assisted reproductive technologies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Perceived barriers to effective infertility care. RESULT(S): Arab Americans and African Americans living in metropolitan Detroit are at increased risk of infertility and share similar histories of poverty, racism, and cultural barriers to medical treatment. This study, which focused on infertile Arab American men living in or near Dearborn (an ethnic enclave community composed mainly of recent immigrants and war refugees), revealed significant barriers to effective infertility care, including economic constraints, linguistic and cultural barriers, and social marginalization in mainstream U.S. society, particularly after September 11, 2001. CONCLUSION(S): Arab Americans experience disparities in access to infertility care, largely because of poverty and social marginalization in post-September 11th America.

Adult↗

Unmet need for reproductive health in India.

Using data from the National Family Health Survey of 1992-93 and the individual reproductive histories of a cross-section of 70 women from rural Tamil Nadu, this paper exposes the limited extent to which women in India have been able to achieve their reproductive intentions and the failure of health services to meet their considerable reproductive health needs. Of the 70 women, 69 had been unable to achieve their reproductive intentions, not only non-users of contraception but also ever-users, and all 69 had an unmet need for reproductive health services. Sterilisation is often the first and only method of contraception taken up and only after a series of wanted, mistimed and unwanted pregnancies, miscarriages, induced abortions and neonatal and infant deaths. Women who wanted to have more children than they were able to were also found. Given the paradigm policy shift in India from promoting fertility reduction only to meeting women's reproductive and sexual health needs, a more useful concept for measuring 'unmet need' for services in programme planning is required, one such as the HARI index, that would capture the extent to which individual women are achieving their reproductive intentions in good health. Without this, the same problems will only recur in younger women.

Birth Intervals↗

Nuclear industry family study:methods and description of a United Kingdom study linking occupational information held by employers to reproduction and child health.

OBJECTIVE: To describe the methods used in the nuclear industry family study for which a comprehensive database has been assembled that links employment in the nuclear industry and dosimetry records to information on employees' reproductive health and the health of their children. To discuss the response rates and characteristics of the study population. METHODS: Occupational cohort design leading to a retrospective cohort study of reproductive outcomes reported by 46 396 current and former employees of both sexes in the nuclear industry. Employees of nuclear establishments in the United Kingdom operated by the Atomic Energy Authority, the Atomic Weapons Establishment, and British Nuclear Fuels were surveyed with postal questionnaires ot collect information on pregnancies, children,and periods of infertility. Information on employment and monitoring for ionising radiation was supplied by the employing nuclear authority and was linked to pregnancies and periods of infertility with unique personal identification numbers. RESULTS: The design and completion of this study resulted in high quality data on a representative population of the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels workforces. The response to the survey was extremely good (82% for male workers and 88% for female workers, excluding undelivered questionnaires), and a unique relational database has been created which will enable infertility, pregnancy, and child health outcomes to be examined with respect to the employment and radiation monitoring characteristics of parents. CONCLUSION: This is the first United Kingdom study to link detailed reproductive history data to occupational information held by employers. The methods developed for the study were found to be feasible and successful. The design can be adapted for other investigations of reproductive hazards to men and women in the workplace and is currently in use to survey over 100 000 armed forces personnel in an investigation of reproductive outcome among veterans of the Gulf war.

Adult↗

Frequent reproductive cycling: does it lead to nutritional depletion of mothers?

Is frequent reproductive cycling (episodes of pregnancy and/or lactation) in poor women from developing countries a cause of poor maternal nutritional status? This review seeks to examine the evidence available to answer this question. The measurement of reproductive cycling, maternal nutritional status, and the energetic costs of pregnancy and lactation are reviewed. The data available on the anthropometric changes during pregnancy and lactation are described. Against this background, the evidence in support of the hypothesis that repeated reproductive cycling leads to a maternal depletion syndrome is examined. It is concluded that although the data are inadequate to unequivocally establish or rule out the existence of maternal nutritional depletion due to a demanding reproductive history, the data suggest this relationship does exist. Weaknesses of current measurement and study design methodologies are identified and priorities for future research aimed at clarifying the extent to which reproductive cycling affects maternal nutritional status are identified.

Developing Countries↗

Lactation history and bone mineral density among perimenopausal women.

To examine the relation between lactation and bone mineral density, we conducted a cross-sectional study among white, nonsmoking, perimenopausal women age 40-54. Three hundred fifty-two women completed a questionnaire covering medical and reproductive histories, physical activity, and diet. We measured the bone density of lumbar vertebrae 2-4 with dual photon absorptiometry, and the midradius and distal radius with single photon absorptiometry. Women with a history of lactation had 41 mg per cm2 higher lumbar bone mineral density than women with no lactation (95% confidence interval = 8-74 mg per cm2), controlling for parity, body mass, physical activity, and menopausal status. We found no important increase at mid- or distal radius.

Adult↗

Chromosome abnormality in couples with histories of multiple abortions. The outcome of pregnancies subsequent to ascertainment and a study of familial translocation carriers.

A series of couples with histories of recurrent abortions and in whom one partner had been shown to have a major chromosomal anomaly were investigated with respect to the karyotypes of conceptions subsequent to ascertainment. The reproductive histories of translocation carriers amongst relatives were also studied. Results were compatible with previous reports of the behaviour of translocation chromosomes at meiosis with an additional previously undescribed outcome as a result of a maternal 13/14 Robertsonian translocation.

Abortion, Habitual↗

Reproductive pattern in consanguineous and non-consanguineous marriages in La Cabrera, Spain.

BACKGROUND: Among determinants of the structure of human populations, consanguineous marriages can be useful in determining to what extent they influence the genetic structure of the population. This knowledge may be gained by comparing the reproductive performance of related and non-related couples. The population studied, La Cabrera, is a mountainous region in the Leon province (north-western Spain). It includes four neighbouring municipalities with similar geographic, climatic and ecological features with 37 parishes occupying an area of 784.2 km(2), of which only 1.5% is arable. The number of inhabitants remained stable from 1887 (9526 inhabitants) to 1960 (8984), when due to emigration it began to decrease. The average inbreeding coefficient (alpha) for the period 1880-1989 (up to third degree) was 4.82 x 10(-3). AIM: The objective of this analysis was to evaluate the possible factors determining the differences between consanguineous and non-consanguineous families residing in La Cabrera during the period 1880-1959. SUBJECTS AND METHODS: To study the structure and dynamics of each couple, families were reconstituted for the period 1880-1959 using demographic data corresponding to births, deaths and marriages obtained from parish registers. This procedure provided information on each couple's reproductive history through information concerning the mates' deaths as well as their offspring's births and deaths. Principal component analysis revealed the existence of three factors that together explained 57% of the reproductive pattern variability of La Cabrera. RESULTS: The first component (eigenvalue: 3.56) correlated positively with the number of live births and with the duration of the reproductive period. Component II (eigenvalue: 1.54) had a positive correlation with variables describing the beginning of the marital union, and with those indicating its ending. Finally, component III (eigenvalue: 1.13) reflected a negative association with the two variables that described neonatal and post-neonatal mortality. The above demographic variables represented the reproductive process in La Cabrera adequately. Fertility was the variable that offered the best explanation of the reproductive pattern (32%), followed by the marital structure (13%) and the infant mortality (12%). CONCLUSION: In the La Cabrera population, consanguinity appears as a socio-cultural process that affects the reproductive dynamic. Consanguinity modifies the marital structure and alters the reproductive pattern, prolonging the reproductive period, which results in a greater number of offspring. Lower infertility rates and the possible compensatory effect for infant mortality may reflect biological factors making the wife's reproductive period more efficient.

Adult↗

X chromosome aneuploidy in lymphocyte cultures from women with recurrent spontaneous abortions.

Occasional metaphases with X chromosome aneuploidy can be detected in short-term lymphocyte cultures from women with recurrent abortions. The significance of this finding is unknown. It has been suggested that it may reflect a genetic tendency to nondisjunction that predisposes these women to an increased risk of producing aneuploid offspring. We have investigated prospectively the frequency of X chromosome aneuploidy in lymphocyte cultures from 104 women with a normal chromosome constitution and a history of recurrent pregnancy loss defined as 2 or more spontaneous abortions. Seventeen women (16%) had a significant number (2-10%) of X aneuploid cells in cultured lymphocytes but no evidence of constitutional chromosome mosaicism, based on analysis of fibroblast cultures. A control group of age-matched fertile women without a history of recurrent abortions showed a similar level of X chromosome aneuploidy in lymphocyte cultures. No increased risk for production of liveborn children with aneuploidy was found on retrospective analysis of the reproductive histories of these women. A significant effect of culture conditions on X chromosome gain or loss has been demonstrated by comparison of medium 199 with Dulbecco's modified Eagle medium.

Abortion, Habitual↗

Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer.

There are sex differences in the occurrence of microsatellite instability (MSI) in colon tumors. Taken together with the epidemiological evidence that hormone replacement therapy (HRT) and, less consistently, parity, are inversely associated with colon cancer, it has been hypothesized that estrogens are associated with MSI. The purpose of this study was to evaluate sex-specific differences in the prevalence of MSI in colon tumors and to determine whether reproductive history and hormonal exposures are associated with MSI. Using data from a population-based case-control study of 1836 cases with MSI data and 2410 population-based controls, we evaluated sex, reproductive factors, and hormone exposure in relation to the presence or absence of MSI in tumors. MSI was evaluated by a panel of 10 tetranucleotide repeats, the noncoding mononucleotide repeat BAT-26, and the coding mononucleotide repeat in transforming growth factor beta receptor type II (TGFbetaRII). Exposure data on reproduction, hormone use, obesity, and physical activity were obtained from an interviewer-administered questionnaire. Women were less likely then men to have MSI+ tumors at a young age and more likely to have unstable tumors at an older age; we observed a significant interaction (P < 0.01) between age, sex, and MSI. Evaluation of reproductive factors showed that women who had ever been pregnant had half the risk of MSI+ tumors compared with women who had never been pregnant. In complementary fashion, total ovulatory months were associated with an increased risk of MSI+ tumors [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-4.0 comparing MSI+ versus MSI- tumors]. Age at first and last pregnancy did not influence the association. The observed associations were strongest among women <60 years of age at the time of diagnosis. Having used oral contraceptives was associated with a lower risk of MSI+ tumors (OR, 0.7; 95% CI, 0.4-1.2); recent users of HRT were at a reduced risk of MSI+ tumors (OR, 0.8; 95% CI, 0.5-1.4); and women who were former HRT users were at an increased risk of MSI+ tumors (OR, 1.8; 95% CI, 1.1-3.0). Obesity and lack of physical activity were associated with an elevated risk of both MSI+ (OR, 1.7; 95% CI, 0.7-3.3) and MSI- (OR, 2.2; 95% CI, 1.7-3.) tumors in men, but only with MSI- (OR, 1.5; 95% CI, 1.1-2.2) tumors in women. The excess of MSI+ tumors in women is explained by the excess of MSI+ tumors at older ages. Our data suggest that estrogen exposure in women protects against MSI, whereas the lack of estrogen in older women increases risk of instability. HRT in these older women may, again, reduce the risk of unstable tumors. A model for the way in which estrogens (endogenous, exogenous, and obesity-associated) modify the risk of MSI+ tumors is proposed.

Adipose Tissue↗

Predictors of menopausal hot flashes.

There are limited data on the factors associated with menopausal hot flashes, a common and potentially morbid condition. The objective of this study was to identify predictors of menopausal hot flashes. To meet this objective, 233 naturally perimenopausal or post-menopausal women (ages 45-65) attending a large urban hospital center primary care clinic, mammography unit, or women's health practice were enrolled. The women responded to a self-administered questionnaire assessing selected demographic factors, reproductive history, and behavioral factors. Sixty-seven percent of respondents experienced hot flashes, with 63% reporting frequent hot flashes (at least one hot flash per day) and 60% with hot flashes describing the hot flashes as severe. Women with hot flashes were significantly more likely to have mothers who experienced hot flashes (OR = 4.4, CI = 2.0-10.0) or to be smokers (OR = 2.0, CI = 1.2-3.5). There were no statistically significant associations between hot flashes and other selected demographic, reproductive, or behavior characteristics. These results reveal that menopausal hot flashes are associated with a maternal history of hot flashes as well as with cigarette smoking. These results may help physicians to counsel their patients about smoking cessation.

Aged↗

Sociality and individual fitness in yellow-bellied marmots: insights from a long-term study (1962-2001).

Theoretical and empirical studies suggest that the age of first reproduction (the age at which reproduction begins) can have a substantial influence on population dynamics and individual fitness. Using complete survival and reproductive histories of 428 female yellow-bellied marmots (Marmota flaviventris) from a 40-year study (1962-2001), we investigated causes and fitness consequences of delayed maturity. Most females (86%) died without reproducing. The age of first reproduction of females that survived to reproduce at least once (n=60) ranged from 2 to 6 years. Females maturing later did not have a larger lifetime number of successful reproductive events or offspring production, nor did they experience improved survival. Females reproducing earlier had a higher fitness than those that delayed maturity. These results suggest that the net cost of early maturity was less than fitness benefits associated with early onset of reproduction, and that age of first reproduction in our study population is under substantial directional selection favoring early maturity. We conclude that female yellow-bellied marmots delay onset of reproduction not because of fitness benefits of foregoing reproduction at an earlier age, but due to the social suppression of reproduction by older, reproductive females, which enhances their own fitness to the detriment of the fitness of young females. Our results indicate that female yellow-bellied marmots that survive to reproduce may act to increase their own direct fitness, and that social suppression of reproduction of young females is a part of that strategy.

Adaptation, Physiological↗