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PubMed1991

Parity factors and prevalence of fibrocystic breast change in a forensic autopsy series.

The relationship of reproductive factors, such as nulliparous vs ever-parous status, age at first birth, and total parity, with morphologic prevalence of fibrocystic changes were examined using autopsy material from three ethnic/racial groups at varying risks for breast cancer. Although there was a trend toward a protective effect of ever-parous status, there was no statistically significant difference in the prevalence of fibrocystic disease in any group defined by parity status. The ethnic differences in the prevalence of fibrocystic changes were not explained by the differences in parity status distribution for the three ethnic/racial groups.

Adolescent↗

PubMed1996

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.

Adult↗

PubMed1996

Reproductive factors and prognosis of uterine cervical cancer in Norway.

Based on Norwegian registry and census data, the influence of reproductive factors on excess mortality from cervical cancer was examined. Parity level had no impact on the excess mortality. In parous women, a beneficial effect of an early first birth was found, most pronounced in 20- to 39-year-old women with squamous cell carcinoma.

Adult↗

PubMed1998

Do urinary oestrogen metabolites predict breast cancer? Guernsey III cohort follow-up.

This is the first prospective study of urinary measures of the two major competing pathways of oestrogen metabolism, 16alpha-hydroxyoestrone (16alpha-OHE1) and 2-hydroxyoestrone (2-OHE1), in relation to incident breast cancer risk. Experimental and case-control study results suggest that metabolism favouring the more oestrogenic 16alpha-OHE1 pathway may be linked to higher breast cancer risk. Women aged 35 and older from Guernsey (n = 5104) were surveyed in 1977-85 and have been continuously monitored for breast cancer and mortality up to the present (Guernsey III, Imperial Cancer Research Fund). Incident cases of breast cancer were matched to three control subjects for comparison of urinary oestrogen metabolite levels measured by enzyme immunoassay (EIA) in spot urine samples collected at baseline and stored frozen for up to 19 years. Consistent with case-control study results, post-menopausal (but not premenopausal) women at baseline who went on to develop breast cancer showed about a 15% lower 2:16alpha-OHE1 ratio than matched control subjects. Further, subjects with metabolite ratios in the highest tertile of 2:16alpha-OHE1 had about a 30% lower risk than women with ratios in the lowest two-thirds, although results were not statistically significant (OR = 0.71, 95% CI = 0.29-1.75). It is of potential importance that, in contrast to most risk factors for breast cancer, such as late age at first birth, oestrogen metabolism appears to be modifiable via diet and exercise, offering women the possibility of lowering breast cancer risk through non-pharmacological measures, although this remains to be tested.

Adult↗

PubMed2003

Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National Case-Control Study of Cervical Cancer.

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20-44 years from the UK National Case-Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of sexual partners, and, independently, to age at first intercourse. The risk of both types of cervical cancer increased with increasing duration of use of oral contraceptives, and this effect was most marked in current and recent users of oral contraceptives. The risk of squamous cell carcinoma was associated with high parity and the risk of both squamous cell and adenocarcinoma increased with early age at first birth. Long duration smoking (20 or more years) was associated with a two-fold increase in the risk of squamous cell carcinoma, but smoking was not associated with the risk of adenocarcinoma. Further studies are needed to confirm the suggestion from this and other studies of differences in risk related to smoking between squamous cell and adenocarcinomas of the cervix.

Adenocarcinoma↗

PubMed2006

Cancer risk among users of neuroleptic medication: a population-based cohort study.

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25,264 users (>or=2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989-2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41-0.91) and 0.82 (0.56-1.19), respectively) and for colon cancer in female users (0.78; 0.62-0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69-1.08), but breast cancer risk was close to unity (0.93; 0.74-1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.

Adolescent↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2001

Hospitalization for early bonding of the genetic mother after a surrogate pregnancy: report of two cases.

BACKGROUND: In surrogate pregnancies the genetic parents have little opportunity for early bonding to their infant, either prenatally (in utero) or in the immediate postnatal period. The purpose of this article is to describe a new method for encouraging early parent-infant bonding after surrogate pregnancy by hospitalizing the genetic mother in the maternity ward immediately after the delivery. METHODS: Two genetic mothers were hospitalized in the maternity ward (rooming-in system) at the Rabin Medical Center in Israel immediately after delivery of their infants by surrogate arrangement. The first birth was a singleton pregnancy with vaginal delivery and the second, a twin pregnancy with delivery by cesarean section. The genetic parents were counseled by a social worker from the adoption agency, starting 3 months before the estimated date of delivery. The parents were referred to the hospital social worker before the delivery. To assess attachment, we observed the parents' behavior toward their children during two daily 15-minute periods of free, unstructured interaction. RESULTS: The parents showed good primary caregiving functions and established affective verbal and physical contact with the infants. They began to recognize the infants' needs and temperament, and exhibited an aura of self-confidence during their interactions. All expressed satisfaction with the method at discharge and reported on reduction of their fears about returning home with the infants. CONCLUSIONS: We believe that early hospitalization of the genetic mother in a surrogate delivery may be desirable to establish good and safe early mother-infant bonding, and that it should be considered for adoption as regular hospital policy. Further randomized studies with larger samples over the long term are warranted.

Adult↗

PubMedDate not supplied

From adjuvant therapy to breast cancer prevention: BCPT and STAR.

The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women > or = 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women > or = 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events.

Antineoplastic Agents, Hormonal↗

PubMed2000

Immature germ cell conception-in vitro germ cell manipulation.

Experimental studies in laboratory animals have shown that successful conception can be achieved by fertilizing oocytes with immature male germ cells. This gave rise to the concept that immature germ cells recovered from the testes of azoospermic men with maturation arrest may be used for assisted reproduction. However, in contrast to using germ cells recovered from healthy animals, clinical application to the treatment of male sterility is burdened by inherent defects in germ cells attributable to underlying testicular pathology. The recent introduction of in vitro germ cell culture/manipulation techniques makes it possible, in some cases, to overcome the in vivo maturation arrest by allowing an additional meiotic and post-meiotic differentiation and the selective harvesting of cells devoid of apoptosis-related nuclear and cytoplasmic damage. These techniques enabled the first births of normal infants fathered by azoospermic men with maturation arrest at the primary spermatocyte stage and improved the efficacy of assisted reproduction in men with maturation arrest at the round spermatid stage.

Animals↗

PubMed2005

Ultrasound screening for congenital pyelectasis in term pregnancies.

The purpose of this study was to compare the role of antenatal ultrasound screening for congenital pyelectasis at term with postnatal screening. An ultrasonographic prospective study of 231 fetuses of low-risk pregnancies was performed, evaluating the renal pelvis at term (38 to 42 weeks gestation) and after birth (first and third months of life). Cut-off points used were 9 mm antenatally, and 10 and 12 mm, respectively postnatally, all in an anteroposterior view. A sensitivity of 20% and a specificity of 93.4% was obtained when comparing the antenatal versus the third-month scan, whereas when we compared the sonograms from the first versus the third month of life, we found a sensitivity of 60% and a specificity of 89.7%, with a positive predictive value of 14.7% in the first case and 25% in the second case. A p value < 0.001 was obtained when comparing the sensitivities; a p value of 0.2 was reported when comparing the specificities. Data on a comparative screening of the renal pelvis measured antenatally at term and postnatally do not exist. Although it is extremely feasible, the measurement of the fetal renal pelvis during the routine ultrasound scan at term of gestation seems of no benefit in terms of sensitivity and positive predictive values in identifying infants affected by congenital pyelectasis. Because of the low values of sensitivity obtained in our study, a screening program for the renal pelvis dilation both in fetuses and newborns cannot be recommended.

Female↗

PubMed2005

Cryopreservation in assisted reproductive technology: new trends.

During the last few years, cryopreservation has become a relevant addition to therapeutic concepts in reproductive medicine. New data and publications have made it difficult to maintain an overview of all of the new developments and their results. The focus of interest more recently, especially with the cryopreservation of human oocytes and human ovarian tissue, has been vitrification as an interesting alternative to slow freezing methods. Even though studies investigating the slow freezing of human mature oocytes have resulted in very different survival rates, it could be an option for donor oocyte programs, in the case of threatened ovarian loss or when there is an objection to embryo freezing. An optimal freezing protocol and later use of thawed human ovarian tissue is still a point of discussion. There are encouraging results regarding different kinds of autotransplantation, and recently the first birth after orthotopic autotransplantation of cryopreserved/thawed human ovarian tissue was described in the literature. Independent of any objections to cryopreservation in general, vitrification is a potential and effective alternative to conventional slow cryopreservation, especially for oocytes and embryos. Vitrification might be also be an option for human ovarian tissue; however this is only in its infancy and requires much additional investigation. Our article discusses new trends and results of actual studies regarding these issues.

Cryopreservation↗

PubMed1990

[Incidence and prognosis of breast cancer in young women in relation to changes in the risk factor profile].

Trends in breast cancer incidence in women aged 25-44 years are assessed in detail based on data from the population-based cancer registry of Saarland-Germany. Compared to 1968-72, from 1978-82 and 1983-87, a highly significant increase in age-standardised incidence by more than 30% was observed. The increase in incidence was most pronounced among women of 25-29 years of age (relative incidence rate 1978-87, compared to 1968-77: 2.03, 95% confidence interval: 1.11-3.71). The role of changes in prevalence of known and suspected risk factors, mainly the age at the onset of menarche, the age at first birth, parity and early and long-term use of oral contraceptives in adolescence, which may partly explain the observed trends, are discussed. The results have important public health implications, such as the need for extended cancer surveillance and epidemiologic research in the Federal Republic of Germany, and offer a quantitative basis for the development and implementation of future early detection programmes as well as the need for medical care facilities.

Adult↗

PubMed2002

Low serum level of mannan-binding lectin is a determinant for pregnancy outcome in women with recurrent spontaneous abortion.

OBJECTIVE: The purpose of this study was to investigate the genetic background for the previously reported finding of an increased frequency of low levels of mannan-binding lectin in couples with unexplained recurrent spontaneous abortion and to evaluate the impact of low mannan-binding lectin levels on future pregnancy outcome. STUDY DESIGNS: Mannan-binding lectin levels were measured in 217 women with unexplained recurrent spontaneous abortion and 111 of their husbands and were compared with corresponding measurements in 104 couples with uncomplicated reproductive histories and 210 blood donors. An investigation of the genetic polymorphism, which is largely responsible for serum mannan- binding lectin levels, was done by polymerase chain reaction methods with DNA from a subset of the patients and control subjects. Information was collected about the outcome of the patients' next pregnancies, together with perinatal data concerning the patients' first birth that occurred before or after being assigned to the study. RESULTS: Among women with recurrent spontaneous abortion, 18.9% of the women had mannan-binding lectin levels of </= 100 ng/mL compared with 12.2% of control subjects ( P =.02). An investigation of mannan-binding lectin levels and genetic analyses gave no evidence that paternal mannan- binding lectin deficiency plays a role for recurrent spontaneous abortion. Patients with mannan-binding lectin levels of </=100 ng/mL had a higher abortion rate than patients with normal mannan- binding lectin levels (P <.05). The median birth weight of children who were born at term of women with recurrent spontaneous abortion was 287 g less in women with mannan-binding lectin levels of </= 100 ng/mL than that of patients with normal mannan-binding lectin levels (P =.04). CONCLUSION: Low maternal serum mannan-binding lectin levels exhibit a negative impact on pregnancy outcome in women with unexplained recurrent spontaneous abortion.

Abortion, Habitual↗

PubMed2005

The path to lowest-low fertility in Ukraine.

The phenomenon of lowest-low fertility, defined as total fertility below 1.3, is now emerging throughout Europe and is attributed by many to postponement of the initiation of childbearing. Here an investigation of the case of Ukraine, where total fertility--1.1 in 2001--is one of the world's lowest, shows that there is more than one pathway to lowest-low fertility. Although Ukraine has undergone immense political and economic transformations in the past decade, it has maintained a young age at first birth and nearly universal childbearing. Analyses of official national statistics and the Ukrainian Reproductive Health Survey show that fertility declined to very low levels without a transition to a later pattern of childbearing. Findings from focus-group interviews are used to suggest explanations of the early fertility pattern. These include the persistence of traditional norms for childbearing and the roles of men and women, concerns about medical complications and infertility at a later age, and the link between early fertility and early marriage.

Adult↗

PubMed1998

Pregnancy outcome in the elderly primigravidae.

We assessed the effect of advancing maternal age ( 35 years) on the outcome of pregnancy in first births among 50 elderly primigravidae compared with a control group of 50 younger primigravidae (20-29 years) at the University College Hospital Ibadan from 1 January 1988 to 31 December 1992. Most of the elderly primigravidae were professionals and the majority of them (68%) had involuntary infertility. Frequent hospital admissions, preterm delivery, low birth weights and very high caesarean section rates were the major problems highlighted in the elderly primigravidae, while anaemia was more frequent in the younger primigravidae. Unnecessary caesarean sections on the excuse of 'precious' baby in the elderly primigravidae should be discouraged bearing in mind its medico-social implications. It is concluded that although the elderly primigravidae may have higher rates of complications of pregnancy, delivery and neonatal deaths their overall risk of referral to special care baby unit is not appreciably increased.

Journal Article↗

PubMed1977

Age at puberty in relation to age at marriage and parenthood: a national longitudinal study.

A longitudinal study of a British cohort has collected information on puberty, judged by menarcheal age for the girls and the pubertal stage of the boys at age 14 3/4. This information has now been related to the ages at which these young people married and became parents. For the young men there was evidence of a direct relationship between degree of sexual maturity at age 14 3/4 and their ages at entry into marriage and fatherhood. For the young women, if pregnancy did not intervene between menarche and marriage, there was evidence of a direct relationship between menarcheal age and marriage age. But there was no evidence that these earlier-maturing young women became mothers at earlier ages than later maturers. This arose through the later-maturing young women having shorter first birth intervals than the earlier maturers. Premarital conceptions were also more prevalent amongst the later maturers.

Aging↗

PubMedDate not supplied

Dermal ridge patterns and fertility in a Polish rural sample.

The relationship between ridge counts and pattern intensities on fingers, palms and soles, and number of pregnancies, number of surviving children, maternal age at birth of first child, and miscarriages was investigated in a rural Polish sample of 273 females. All subjects had completed their reproduction by the time of investigation and the use of contraceptives was negligible. Results show that females with a history of miscarriage have lower mean ridge counts on all fingers and lower pattern intensity on all fingers except V, with statistically significant differences for fingers III and IV. The results also suggest a relationship between the intensity of patterns on fingers II and V and in thenar areas, with the number of pregnancies and/or surviving offspring. The limitations of the present data and a need for more specific investigations are discussed.

Abortion, Spontaneous↗