BACKGROUND: The aim of the study was to explore the extent to which accelerated ovarian ageing may lead to subfertility early in reproductive life and eventually cause early menopause. METHODS: The population studied (n = 2393) never used oral contraceptives, hormone replacement therapy or an intrauterine device. Logistic regression analyses were performed using age at menopause as proxy for accelerated ovarian ageing. Measures of ovarian ageing and subfertility were menstrual cycle irregularity, ever consulted a physician for fertility problems, nulliparity, uniparity, miscarriage(s) and time interval >5 years between birth of first and second child. RESULTS: For every 5 years later menopause, the probability of reporting menstrual cycle irregularity was reduced by 26% (OR = 0.74, 95% CI: 0.63-0.86); the probability of ever consulting a physician for fertility problems was reduced by 18% (OR = 0.82, 95% CI: 0.71-0.95); the probability of staying nulliparous was reduced by 22% (OR = 0.78, 95% CI: 0.64-0.96); the probability of being uniparous was reduced by 22% (OR = 0.78, 95% CI: 0.66-0.91); the probability of having a miscarriage was reduced by 11% (OR = 0.89, 95% CI: 0.79-1.01); the probability of a large time interval between birth of first two children was reduced by 27% (OR = 0.73, 95% CI: 0.61-0.89). CONCLUSIONS: Fertility problems are frequently followed by early menopause. The findings support the view that both are an expression of accelerated ovarian ageing. (+info)
Increased risk of early menopausal transition and natural menopause after poor response at first IVF treatment.
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BACKGROUND: Our aim was to examine whether women who had a low number of retrieved oocytes at their first IVF attempt reach the menopausal transition and/or the natural menopause earlier than women of similar ages with a high number of retrieved oocytes. METHODS: We conducted a retrospective cohort study among women in The Netherlands who received IVF treatment between 1983 and 1995. For the present study, we selected all cohort members who had a regular menstrual cycle at the time of the first visit to the gynaecologist (n = 4601). After a median follow-up of 5.5 years, 3871 (84%) women still had a regular menstrual cycle pattern, 547 (12%) women had entered the menopausal transition (i.e. no menses for 3-11 months, use of HRT or irregular menstrual cycles) and 27 (1%) women had reached natural menopause. We examined whether the quantity and the quality of the retrieved oocytes were related to an early menopausal transition and early menopause. The live birth rate per embryo transfer was used as indicative of the quality of the oocytes. RESULTS: The age-adjusted odds ratio (OR) for having entered the menopausal transition/natural menopause for women with a poor response (0-3 oocytes) at their first IVF attempt was 3.1 [95% confidence interval (CI) 2.4-3.8] compared with women with a normal response (>3 oocytes). Women who were stimulated with gonadotrophins during IVF treatment but did not undergo an IVF puncture because of an anticipated poor response (cancelled IVF cycle) had an age-adjusted OR of 3.2 (95% CI 2.3-4.3). There was no significant difference in the odds of reaching the menopausal transition/natural menopause, after adjustment for age and the number or retrieved oocytes, between women who did and did not have a live birth following their first embryo transfer (OR = 1.3; 95% CI 0.95-1.7). CONCLUSIONS: These results indicate that a low remaining quantity of oocytes, as reflected by a low number of retrieved oocytes at first IVF treatment, is an important predictor of the risk of an early menopausal transition/natural menopause. The quality of the oocytes did not affect the risk of an early menopausal transition/natural menopause once the number of retrieved oocytes had been taken into account. Our findings support the concept that the number of remaining follicles in the ovaries is one of the main aspects of reproductive ageing. (+info)
Prevention of coronary hyperreactivity in preatherogenic menopausal rhesus monkeys by transdermal progesterone.
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OBJECTIVE: To test if transdermal progesterone (P) confers coronary vascular protection in surgically menopausal preatherosclerotic rhesus monkeys. METHODS AND RESULTS: Ovariectomized rhesus monkeys fed an atherogenic diet (AD) for 19 months were treated with an investigational transdermal P cream (n=7) or identical placebo cream (n=5) for 4 weeks. Aorta and carotids showed fatty streaks and Oil Red O staining demonstrated lipid deposition. Serum P levels in P-treated rhesus monkeys (0.6 ng/mL) were significantly greater than placebo (0.2 ng/mL). Significant elevation of cholesterol, LDL cholesterol, and HDL cholesterol, was noted in all animals. Lp(a) was significantly attenuated in the AD-fed P-treated monkeys. Coronary angiographic experiments stimulating vasoconstriction by intracoronary injections of serotonin plus U46619 showed exaggerated prolonged actions amplified by AD, but significant protection against severe prolonged vasoconstriction in P-treated monkeys. Immunocytochemistry confirmed co-expression of P and thromboxane prostanoid (TP) receptors in coronaries and aorta. Western blotting demonstrated TP receptor attenuation in vascular muscle after P treatment. CONCLUSIONS: Coronary hyperreactivity, a putative component of coronary artery disease mediated via increased vascular muscle thromboxane prostanoid receptors, can be prevented by subphysiological levels of P, not only in nonatherosclerotic (previously shown) but also in preatherosclerotic primates. (+info)
A susceptibility gene for premature ovarian failure (POF) maps to proximal Xq28.
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Terminal deletions of the long arm of the human X chromosome have been described in women with premature ovarian failure (POF). We report here the molecular characterization of an inherited deletion in two affected women and in their mother. The two daughters presented secondary amenorrhea at 17 or 22 years respectively, while the mother was fertile. She had four children, but she eventually had premature menopause at 43 years of age. The fine molecular analysis of the deletion showed that the three women carried an identical deletion. We conclude that the phenotypic difference within the family must be attributed to genetic or environmental factors and not to the presence of different extent deletions. By comparison with other deletions in the region, we map a susceptibility gene for POF to 4.5 Mb, in the distal part of Xq. (+info)
Acute efficacy of a sublingual dose of nifedipine on uterine arterial blood flow: preliminary data in prematurely menopausal women.
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OBJECTIVES: To determine whether the calcium blocker nifedipine alters Doppler velocimetry and impedance parameters in the uterine artery in prematurely menopausal women. METHODS: Uterine artery Doppler examinations were performed transvaginally in seventeen prematurely menopausal women without the use of calcium blocker (T0). Following a 10-mg sublingual dose of nifedipine patients were subsequently rescanned at successive time intervals (T25 = 25, T40 = 40, T60 = 60 min). PI (normalized (NPI) for heart rate) and maximum, minimum and average velocities of the uterine artery were recorded and waveforms were qualitatively assessed using Goswamy and Steptoe's waveform classification. RESULTS: Quantitative analysis showed a significant decrease in NPI at T(25) in the right and left uterine arteries (T0: PI = 2.95 and 3.01; T25: PI = 1.52 and 1.52, respectively; P < 0.001) and until the end of the experiment. Minimum and average blood flow velocities increased strongly (P < 0.001) whereas the maximum velocities did not change significantly (P = 0.12). Qualitative analysis revealed more conspicuous results: eight subjects presented 'abnormal' spectra: one was type A (absence of protodiastole), three were type B (absence of telediastole) and four were type O (no diastolic blood flow); all of them recovered type C waveforms (normal spectrum) during the hour following nifedipine administration. CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in blood flow velocities in the uterine artery in prematurely menopausal women. These results suggest that nifedipine is a potent uterine arterial vasodilator. (+info)
The life mission theory VI. A theory for the human character: healing with holistic medicine through recovery of character and purpose of life.
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The human character can be understood as an extension of the life mission or purpose of life, and explained as the primary tool of a person to impact others and express the purpose of life. Repression of the human character makes it impossible for a person to realize his personal mission in life and, therefore, is one of the primary causes of self-repression resulting in poor quality of life, health, and ability. From Hippocrates to Hahnemann, repression of physical, mental, and spiritual character can be seen as the prime cause of disease, while recovery of character has been the primary intention of the treatment. In this paper, human character is explained as an intersubjective aspect of consciousness with the ability to influence the consciousness of another person directly. To understand consciousness, we reintroduce the seven-ray theory of consciousness explaining consciousness in accordance with a fractal ontology with a bifurcation number of seven (the numbers four to ten work almost as well). A case report on a female, aged 35 years, with severe hormonal disturbances, diagnosed with extremely early menopause, is presented and treated according to the theory of holistic existential healing (the holistic process theory of healing). After recovery of her character and purpose of life, her quality of life dramatically improved and hormonal status normalized. We believe that the recovery of human character and purpose of life was the central intention of Hippocrates and thus the original essence of western medicine. Interestingly, there are strong parallels to the peyote medicine of the Native Americans, the African Sangomas, the Australian Aboriginal healers, and the old Nordic medicine. The recovery of human character was also the intention of Hahnemann''s homeopathy. We believe that we are at the core of consciousness-based medicine, as recovery of purpose of life and human character has been practiced as medicine in most human cultures throughout time. We believe that such recovery can help some (motivated) patients to survive, even with severe disease. (+info)
Association of FMR1 repeat size with ovarian dysfunction.
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BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats). (+info)
Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy.
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PURPOSE: Young women who undergo chemotherapy for breast cancer face serious consequences to their reproductive health. Research in this area has previously focused on men, or on childhood cancer survivors. We sought to explore self-report of reproductive health counseling in young women undergoing chemotherapy for breast cancer. PATIENTS AND METHODS: A total of 166 premenopausal women aged < or = 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues. RESULTS: Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds. CONCLUSION: Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further. (+info)