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[Leptin and human reproduction].

Leptin is a secretory product of adipocytes. It has been suggested that leptin acts as an afferent satiety signal to the brain modulating the expression of the orexigenic hypothalamic peptide, neuropeptide Y (NPY). Therefore leptin can be regarded as a marker of the nutritional status of the body. It was proposed that human obesity may result from a central resistance to leptin due to different pathophysiological mechanisms: saturation of the leptin transport into the cerebrospinal fluid of the obese subjects, abnormalities in the hypothalamic receptor for leptin, or post-receptor transduction mechanisms. It was shown that circulating leptin levels in humans significantly correlate with the body mass index (BMI). Although most studies point to white adipose tissue as a primary source of leptin there is still some uncertainty towards the relative expression of leptin between various body fat compartments. LEPTIN AND ONSET OF PUBERTY: Studies on animal models recognized various metabolic candidates for modulation of GnRH neuronal activity. It was supposed that mild changes in the body's metabolic status can serve to regulate the central drive to the reproductive axis. It is likely that leptin can serve as a "metabolic cue" that transmits signals of those mild metabolic changes towards activation of the GnRH neuronal system at the end of the prepubertal period. On the other side there is a possibility of altered leptin pulsatility during prepubertal period that can consequently influence hypothalamus and GnRH neuronal system. LEPTIN AND SEXUAL DIMORPHISM: Leptin levels in humans are similar in both sexes during the prepubertal period. During puberty leptin has a tendency to decline in boys and to remain constant in girls. Puberty is also characterized with a similar circadian rhythm pattern between sexes whil girls express different pulse characteristics. It seems that sexual dimorphism is established in early phases of human development. There is a possibility of sex steroid influence on such sexual dimorphism. LEPTIN AND REPRODUCTIVE FUNCTION: It was shown that administration of recombinant leptin to ob ob mice could restore fertility in these infertile animals. There is certain difference in leptin levels according to the phase of the menstrual cycle. It was shown that leptin peak is in the luteal phase of the cycle and that correlates to the maximal progesterone level. It is possible that leptin could directly influence ovary and that disruption of such an effect could play a role in menstrual irregularities in both obese and mal nourished women. This could even become a pathophysiological mechanism in women with polycystic ovary syndrome (PCOS). It was supposed that leptin resistance could be involved in infertility impairment of the obese women with PCOS. Leptin increases during pregnancy. Appearance of placenta as a new, nonadipose source of leptin production, increases a possibility of different leptin mRNA expression through gestation.

Adipose Tissue↗

Evolution and dietary restriction.

Placing lifespan in the context of the life history of an organism, Alex Comfort's work has stimulated the analysis of dietary restriction (DR) and its effects on lifespan in an evolutionary context. DR results in the curtailment of energy-intensive nonfood-gathering activities, increased efficiency of food utilization, an increase in food acquisition activity, an increase in the reproductive lifespan, and an increase in the protection of genomic integrity. These result in further refinement of the Adaptive-Longevity Related Process Theory of the effects of dietary modulation to include increased protection of the genomic integrity of cells that result from delayed reproduction, and increased ability to compete for available food. These effects are discussed in the context of the "spacecraft" metaphor for the evolution of senescence. Also, the apparent paradox that increased body weight seems to be directly correlated to survival across species and inversely correlated to survival within a species is discussed in light of the importance of the cephalization index (a modified ratio of brain weight to body weight) for longevity.

Aging↗

Resurgence of active tuberculosis among pregnant women.

OBJECTIVE: To determine the frequency of active tuberculosis during pregnancy in two hospitals located in an area where tuberculosis is epidemic and to describe its course and association with human immunodeficiency virus (HIV) infection. METHODS: We reviewed and analyzed the medical records of 16 pregnant women diagnosed with tuberculosis between 1985-1992 at Kings County Hospital (n = 12) and Saint Vincent's Hospital (n = 4) in New York City. RESULTS: Ten of the 16 pregnant women with proven active tuberculosis had pulmonary tuberculosis, two had tuberculous meningitis, and one each had mediastinal, renal, gastrointestinal, and pleural tuberculosis. Eleven were tested for HIV, and seven were seropositive. One HIV-infected patient with pulmonary tuberculosis died of respiratory failure. In the 6 years between 1985-1990, five cases of active tuberculosis during pregnancy were identified (12.4 per 100,000 deliveries). During the 2 years of 1991-1992, 11 cases were recorded (94.8 per 100,000 deliveries). CONCLUSION: Cases of active tuberculosis are increasing among pregnant women in epidemic communities and are associated with HIV infection. Early tuberculin skin test screening with appropriate preventive therapy should reduce morbidity due to tuberculosis in HIV-infected women of reproductive age. Identification of pregnant women with tuberculosis requires a high index of suspicion.

Adult↗

Management of tuberculosis in pregnancy.

In the United States, escalating rates of homelessness and human immunodeficiency virus infection have provided a background for the resurgence of Mycobacterium tuberculosis. This scourge of tuberculosis has disproportionately affected groups of reproductive-age women who have limited access to health care. Despite wide reporting of an increased incidence of tuberculosis, a low index of suspicion continues to delay diagnosis of the disease in pregnant women. As a result, a newborn diagnosed with congenital infection often becomes the index case for maternal infection. To become proficient in the prenatal diagnosis of tuberculosis, clinicians must make an in-depth review of the clinical signs and symptoms consistent with tuberculosis a routine part of obstetrical screening. Once diagnosed, tuberculosis is treated as aggressively in pregnancy as it is in the nonpregnant patient.

Female↗

Waist-to-hip ratio and judgment of attractiveness and healthiness of female figures by male and female physicians.

Sexual dimorphism in body fat distribution as measured by waist-to-hip ratio (WHR) is unique to humans. The WHR has been shown to be an accurate predictor of risk for various diseases, premature mortality, degree of androgenicity/estrogenicity and fecundity of women, independent of overall body weight. This study investigated whether physicians would be influenced by body size or WHR in assessing health, youthfulness, and reproductive capability of a woman. Line drawings of 12 female figures representing three categories of body weight (normal, underweight and overweight) and four sizes of WHR (0.7, 0.8, 0.9 and 1.0) were ranked by male and female physicians for these qualities as well as for attractiveness and intelligence. Both males and females assigned higher ranking for many of these qualities to normal weight figures with low WHRs (0.7 and 0.8). Overweight figures were assigned low rankings for all these qualities except reproductive capability. Underweight figures, regardless of WHR size, were assigned low ranking for reproductive capability and those underweight figures that had high WHRs (0.9 and 1.0) were assigned low ranking for healthiness. While there were minor sex differences in ranking of some attributes for some figures, generally both male and female physicians utilized the WHR in a similar manner to infer healthiness, reproductive capability and attractiveness.

Adult↗

Reproductive factors, exogenous hormone use and bladder cancer risk in a prospective study.

Sex is a consistent predictor of bladder cancer: men experience 2-4-fold higher age-adjusted rates than women in the U.S. and Europe. The objective of this study was to examine whether hormone-related factors are associated with bladder cancer in women. We examined parity, age at menarche, age at first birth, age at menopause, oral contraceptive use and menopausal hormone therapy (HT) use and bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow-Up Study. Endpoint and exposure information was collected on 54,308 women, using annual telephone interviews (1980-86) and 3 mailed, self-administered questionnaires (1987-98). During an average follow-up time of 15.3 years, 167 cases of bladder cancer were identified. Univariate and adjusted rate ratios (RRs) were estimated using Poisson regression. Parity, age at menarche, age at first birth, age at menopause, and oral contraceptive use were not associated with bladder cancer risk. The majority of menopausal women who took HT used estrogen therapy (ET). Postmenopausal women with less than 4 years, 4-9 years, 10-19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96-2.51), 1.00 (95% CI = 0.49-2.04), 1.23 (95% CI = 0.62-2.43) and 0.57 (95% CI = 0.14-2.34), respectively, compared with nonusers (p = 0.50). Findings from this study are not consistent with the hypothesis that hormone-related factors in women are associated with bladder cancer.

Age Factors↗

Prevalence of menstrual pain in relation to the reproductive life history of women from the Mayan rural community.

BACKGROUND: The prevalence of menstrual pain in Western societies is relatively high and has been shown to be related to many factors (e.g. age, menarche age, parity, menstrual cycle regularity, cigarette smoking, dietary habits). However, less data are available for traditional societies, within which there are, presumably, not as many potentially disturbing factors that could influence menstrual symptoms as in Western societies. AIM: The study seeks to determine the prevalence of dysmenorrhoea, and the factors related to menstrual pains in women with natural fertility (i.e. without hormonal forms of contraception). SUBJECTS AND METHODS: 177 non-smoking women between 18 and 45 years of age living in one Mayan village (Yaxcaba, Yucatan, Mexico) were the subjects of this study. The method of logistic regression was used with the dichotomous dependent variable being the presence or absence of menstrual pain together with such independent variables as age, age at menarche, number of pregnancies, age when giving birth to the first child, the weight at interview and BMI. RESULTS: The general prevalence of the menstrual pains was 28%. There was only one variable influencing dysmenorrhoea, namely the age at which women give birth to their first children. Those mothers who gave birth to their first child at an earlier age (at mean age of 19.4 vs 21.1 years) had a lower prevalence of dysmenorrhoea. CONCLUSION: In the studied traditional society the main factor related to menstrual pain was the age at which woman first gave birth. It is hypothesized that an earlier start to reproductive life in some way decreases the sensitivity of the uterus to prostaglandins.

Adult↗

Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome.

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Adult↗

Evidence for competing effects of body mass, hyperinsulinemia, insulin resistance, and androgens on leptin levels among lean, overweight, and obese women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the relationships between leptin, body composition, insulin resistance, androgens, and reproductive indices among women with polycystic ovary syndrome (PCOS). DESIGN: Matched case-control study. SETTING: Academic reproductive endocrine practice; school of public health. PATIENT(S): Forty-six Caucasian women with PCOS and 46 population-based controls matched by age and body mass index (BMI). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Leptin, insulin, androgenic hormones, body composition parameters; reproductive parameters. RESULT(S): Overall, leptin levels among women with PCOS did not differ significantly from those of control women (20.4 +/- 14.9 vs. 21.9 +/- 14.3 ng/mL). However, within the lowest BMI tertile, women with PCOS had significantly lower leptin levels (9.6 vs. 18.3 ng/mL), comparable insulin, and higher testosterone concentrations than controls of similar body mass. Within the overweight and obese subgroups, both insulin and testosterone levels were increased among women with PCOS; leptin levels, although higher among obese cases, were not statistically different than those in controls. CONCLUSION(S): Below a certain BMI, hyperandrogenic women with PCOS have lower leptin levels than controls. Conversely, overweight and obese PCOS subjects appear to produce insufficient leptin for a given fat mass, relative to the degree of hyperinsulinemia, potentially because of the competing effects of adipocyte insulin resistance and androgens on leptin.

Adult↗

Normal uterine size in women of reproductive age in northern Islamic Republic of Iran.

To determine the efficacy of ultrasonographic assessment of uterus size in women of reproductive age, we conducted a cross-sectional analytic study of 231 women aged 15-45 years in Babol, northern Islamic Republic of Iran. Mean uterus size was 86.6 mm x 49.6 mm x 40.6 mm overall, 72.8 mm x 42.8 mm x 32.4 mm for nulliparous women and 90.8 mm x 51.7 mm x 43.0 mm for multiparous women. Mean age was 31.7 +/- 9.6 years and mean body mass index (BMI) was 24.7 +/- 4.0 kg/m2. Uterus size was significantly associated with parity and age; but not with BMI. Our findings show a greater mean uterus size than reported by others. Ultrasonographic measurement of uterus size is valuable for predicting pathologies associated with abnormal uterine size.

Adolescent↗

The beta 3-adrenergic receptor gene Trp64Arg mutation is overrepresented in obese women. Effects on weight, BMI, abdominal fat, blood pressure, and reproductive history in an elderly Australian population.

A tryptophan to arginine (Trp64Arg) mutation in the beta 3-adrenergic receptor (beta 3-AR) gene has been implicated in diabetes and obesity. We investigated the relationship of the beta 3-AR gene mutation with total body weight, BMI, central abdominal fat, blood pressure (BP), and reproductive history in 686 elderly subjects (429 women, 257 men; mean age 69.8 +/- 6.9 [+/-SD] years) from a cross section of a normal population in Australia. About 14% of the test population were heterozygote carriers of the Trp64Arg mutation; however, significant effects on clinical parameters were only observed in women. The frequency of the mutation was significantly increased in obese women compared with lean women (BMI > or = 27: 20% compared with BMI < 27: 11%, P = 0.02). Significantly higher total body weight (67.5 +/- 12.9 vs. 64.1 +/- 12.2 kg, P = 0.03) and BMI (26.3 +/- 4.7 vs. 25.1 +/- 4.5 kg/m2, P = 0.03) was observed in heterozygote women compared with normal subjects (homozygous for tryptophan). Central abdominal fat was not significantly different, except in women under 70 years, where heterozygotes had 16% higher abdominal fat compared with normal subjects. Female heterozygotes had significantly higher diastolic BP, even after adjustment for age and BMI (88.9 +/- 11.1 vs. 84.2 +/- 10.8 mmHg, P = 0.003) and a longer reproductive life, with an earlier menarche (12.8 +/- 1.3 vs. 13.4 +/- 1.5 years, P = 0.006), a higher gravidity (4.4 +/- 2.4 vs. 3.5 +/- 2.1, P = 0.01), and higher parity (3.8 +/- 2.0 vs. 3.0 +/- 1.9, P = 0.005). Clearly, the beta 3-AR mutation has pleiotrophic effects on a number of physiological systems, including BMI, BP, and reproductive history, perhaps suggesting evolutionary reasons for its maintenance in the population.

Aged↗

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Age Distribution↗

Determinants of age at menopause in women attending menopause clinics in Italy.

OBJECTIVE: We analysed the mean age at menopause and its determinants in 31,000 women attending menopause clinics in Italy. DESIGN: Between 1997 and 2003 we conducted a large cross-sectional study on the characteristics of peri- and post-menopausal women attending a network of first-level outpatient menopause clinics in Italy for general counseling or treatment of menopausal symptoms. Spontaneous menopause was defined as natural cessation of menses for 12 or more months. A total of 31,834 women with spontaneous menopause entered the study. RESULTS: The mean age at spontaneous menopause was 51.2. The age at menopause did not markedly changed with cohort of birth. Higher education was associated with lower age at menopause (51.1 in women with low education versus 51.3 for women with high school or university degree, p<0.05). A higher body mass index (BMI) was associated with later age at menopause. Smokers reported a lower age at menopause (51.2 in nonsmokers versus 51.1 in smokers, p<0.05). A later age at menarche was associated with a later age at menopause. Likewise, lifelong irregular menstrual cycles and higher parity were related with later age at menopause. No association emerged between ever oral contraceptive use and age at menopause. CONCLUSIONS: Low educational level, lower BMI, smoking, early menarche, nulliparity and regular cycles are independently associated with lower age at natural menopause in a large sample of women attending menopause clinics in Italy. However, in absolute terms the effect of these factors in our sample is very small.

Age of Onset↗

Association of diet and other lifestyle with onset of menopause in Japanese women.

OBJECTIVES: To evaluate the cross-sectional relationships of dietary and other lifestyle variables to menopause. METHODS: A total of 4186 female residents aged 45-55 in Takayama City, Japan, responded to a self-administered questionnaire (the response rate was 89.3%). Diet in the past year was assessed by semiquantitative food frequency questionnaire. Using the logistic regression model, associations between study variables and menopausal status were estimated in terms of odds ratio (OR). RESULTS: Nulliparity and lower relative weight were significantly associated with menopause after controlling for age (P < 0.05). The association of smoking with menopause was marginally significant after controlling for age (P = 0.06). Higher intakes of fat, cholesterol, and coffee were inversely and significantly associated with later menopause after controlling for age, total energy, parity, menarche age, and relative weight (ORs for the highest tertiles of fat, cholesterol and coffee intakes were 0.78, 0.79, and 0.70, respectively, P < 0.05). The highest tertiles of calcium and soy product intakes were significantly associated with menopause after controlling for the covariates (ORs = 1.25 and 1.42, respectively, P < 0.05), but postmenopausal women who had menopause at later age showed higher calcium intake than those who had menopause at early age. CONCLUSION: Dietary factors appear to be associated with onset of menopause.

Age of Onset↗

The association of dietary fat and plant foods with endometrial cancer (United States).

OBJECTIVES: To examine the associations of dietary fat and selected plant foods with endometrial cancer in a population-based case-control study. METHODS: Six hundred and seventy-nine incident cases of endometrial cancer diagnosed between 1985 and 1991, and 944 population-based controls completed a 98-item semi-quantitative food-frequency questionnaire and a detailed in-person interview which collected information on endometrial cancer risk factors. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of endometrial cancer, adjusted for age, county, energy intake, hormone use, smoking and, in separate models, for body mass index (BMI: kg/m2). RESULTS: Percent energy from fat was associated with an increased risk of endometrial cancer (highest quintile cf. lowest: OR = 1.8, 95% CI 1.3-2.6), with saturated and monounsaturated fats being the main contributors of risk. There was a stronger association between dietary fat and endometrial cancer among groups with higher circulating estrogen levels (i.e. women with higher BMI, users of unopposed estrogens, non-smokers, and younger age at menarche). Consumption of fruits or vegetables was inversely associated with endometrial cancer risk (highest quintile cf. lowest: OR = 0.65, 95% CI 0.46-0.93 and OR = 0.61, 95% CI 0.43-0.88, respectively). Further adjustment for BMI resulted in little or no attenuation of the ORs and associated CIs. CONCLUSIONS: These results provide support for the theory that a low-fat, high-fruit and high-vegetable diet may reduce the risk of endometrial cancer, and that these dietary factors may act independently of the effect of BMI.

Aged↗

Characteristics of women with cosmetic breast implants compared with women with other types of cosmetic surgery and population-based controls in Denmark.

Herein the authors describe characteristics of women with breast implants compared with women with other types of cosmetic surgery as well as population controls. All women who acquired breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Patient characteristics were obtained through a self-administered questionnaire. The magnitude of differences between patient and control groups was estimated using odds ratios and 95% confidence intervals. Women with breast implants had a significantly lower body mass index and reported a two-fold greater incidence of current smoking compared with women from the general population and compared with women with other cosmetic surgery. Women with implants reported a greater number of full-term pregnancies and were less likely than controls to have had their first birth at age 30 years or older. Women with implants were not more likely than women in either control group to report a history of diseases, including connective tissue diseases, cancer, or depression before their implant surgery. Women with cosmetic breast implants differ from women with other forms of cosmetic surgery and from general population controls with respect to characteristics that may importantly influence health outcomes and that need to be addressed in future breast implant studies.

Adult↗

A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women.

OBJECTIVE: Mood and reproductive function were prospectively evaluated in asymptomatic premenopausal women to determine whether the onset of depression was temporally linked to the perimenopause. METHOD: Twenty-nine asymptomatic, regularly cycling women were monitored longitudinally for an average of 5 years until at least 6 months of amenorrhea occurred. Outcome measures included mood ratings and menstrual diaries completed daily, the Structured Clinical Interview for DSM-IV, and plasma levels of follicle-stimulating hormone obtained at 3-6-month intervals. The number of episodes of depression and their timing relative to the final menstrual period were determined. Differences in outcome measures between women who did and did not become depressed during the perimenopause were determined by Student's t test, chi-square tests, and Fisher's exact test. RESULTS: The authors observed 11 episodes of new-onset depression in nine of the 29 women. In the 24 months surrounding the last menstrual period nine episodes of depression were observed. Six of the nine women who became depressed during the study had no prior depressive episodes. For the 24 months surrounding the final menses, the risk for onset of depression was 14 times as high as for a 31-year premenopausal period of time. Women who developed depression during the perimenopause were not distinguished from those who remained asymptomatic on the basis of symptom profile, duration of the perimenopause, endocrine measures, or past historical variables. CONCLUSIONS: These preliminary data suggest that events related to the late perimenopause may be associated with an increased susceptibility to develop depression in some women.

Adult↗