Hormonal contraception and chemoprevention of female cancers.
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Oral contraceptive (OC) use significantly reduces the risk of endometrial and ovarian cancer, has only a minimal effect on breast cancer, but may increase the risk of cervical cancer. These effects can be readily explained in terms of the effects of OCs on cell proliferation in these tissues. This analysis suggests how a hormonal contraceptive based on a GnRH agonist plus low-dose add-back sex steroids could be made that would greatly reduce lifetime risk of breast and ovarian cancer. Such a hormonal contraceptive is also likely to significantly reduce the lifetime risk of cervical cancer. It is also likely to reduce the risk of endometrial cancer, although not to the same extent as OCs. (+info)
Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood).
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The impact of male age on fecundity remains controversial. Here, a large population study was used to investigate the effect of paternal age on time to conception. All couples in the Avon Health district expecting a baby between 1 April 1991 and 31 December 1992 were eligible. Questionnaires completed by both the man and the woman at 18 weeks gestation covered specific fertility factors, e.g. parity, paternity, cohabitation and oral contraception; and non-specific factors, e.g. educational achievement, housing, cigarette smoking, alcohol consumption, obesity. Logistic regression was used to identify factors independently related to conception in < or =6 or < or =12 months. Of 8515 planned pregnancies, 74% were conceived in < or =6 months, 14% in the second 6 months and 12% after more than a year. Nine variables, including the age of the woman, were independently related to time to conception. After adjustment for these, the likelihood of conception within 6 or 12 months was lower in older men. Compared to men <25 years old, the adjusted odds ratios (95% confidence interval) for conception in < or =12 months were 0.62 (0.40, 0.98), 0.50 (0.31, 0.81) and 0.51 (0.31, 0.86) in men aged 30-34, 35-39 and > or =40 years respectively. (+info)
Continuation rates for oral contraceptives and hormone replacement therapy. The ESHRE Capri Workshop Group.
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Despite the safety and effectiveness of low oestrogen-dose oral contraceptives (OC) and postmenopausal hormone replacement there is poor continuity of use of these agents by women. Patterns of use and the reasons affecting different frequencies of use in different countries are presented. Continuity and discontinuation rates are difficult to assess accurately but it is believed that the main reasons why women discontinue use of these agents are concerns about their perceived health risks and the presence of, or fear of, adverse clinical effects, particularly unscheduled uterine bleeding and weight gain. More information is needed about OC continuation rates in order to improve the acceptability of these safe, effective agents. Most women discontinue use of postmenopausal hormonal replacement within 2 years of initiating the therapy. Reasons include disappearance of symptoms of oestrogen deficiency, lack of awareness of health benefits of oestrogen, presence of side-effects (such as breast tenderness and weight gain), presence of uterine bleeding and increasing age. Suggestions to increase continuation of OC include extensive individual pretreatment counselling with a different emphasis in different age groups, education at the time of follow-up visits and telephone calls, and extensive use of educational aids such as brochures, pamphlets and audio tapes, and improvement of pharmaceutical packaging information. In conclusion there is an urgent need to assess the value of these strategies by long-term large controlled studies. (+info)
Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.
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It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time. (+info)
Humoral hyporesponsiveness to a conjugate contraceptive vaccine and its bypass by diverse carriers using permissible adjuvant.
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A contraceptive vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical testing that demonstrated the feasibility of the approach in preventing pregnancy in women. Some immunized volunteers however, did not respond with an adequate anti-hCG antibody response despite employing highly immunogenic bacterial toxoids as carriers. Since there is some evidence that T cell responses to a complex protein typically focus on a few immunodominant epitopes, we investigated the responsiveness to hCG in mice of different haplotypes using the protein carrier diphtheria toxoid (DT). Our data showed a differential carrier effect of DT. With the aim of making a more potent immunogen employing promiscuous pathogen-derived Th peptides as carriers, peptide:antigen stoichiometric ratios were optimized. When tested individually using alum as the adjuvant, three such peptide conjugates improved the anti-hCG response, though not consistently to levels higher than the DT conjugate. Immunization with a combination of these synthetic epitopes generated anti-hCG responses higher than those achieved with DT or with the individual peptides. Antibodies were of high affinity and capable of neutralizing the bioactivity of hCG, but were devoid of anti-peptide reactivity. These results support our view that differential hyporesponsiveness in a diverse population may arise from inadequate carrier effect and that it can be overcome by use of pathogen-derived broadly reactive non-B Th epitopes employing only alum, a permissible adjuvant. (+info)
Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception.
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Inhibins and activins are dimeric hormones which share common subunits and which have diverse endocrine and paracrine roles in regulating reproductive function. Endometrial expression of inhibin alpha, ssA and ssB subunits was examined by immunohistochemistry and in-situ hybridization, across the menstrual cycle and in early pregnancy. All three subunits were found to be expressed in endometrium, primarily by glandular epithelium in the early stages of the cycle. Following the onset of decidualization, expression of alpha, ssA and ssB subunits was up-regulated in decidualized stromal cells. A marked down-regulation of alpha subunit was detected in glandular epithelium, whilst expression of ssA and ssB subunits was maintained. This pattern was consistent in decidua from early pregnancy and additionally in endometrium from women using progestin-only contraceptives, either subdermal implants (Norplant((R))) or levonorgestrel-releasing intrauterine systems (Lng-IUS). Immunostaining was also observed for both ssA and ssB subunits in subpopulations of endometrial leukocytes, identified to be distinct subsets of macrophages, neutrophils and mast cells. Potential paracrine roles for activins may be envisaged in facilitating tissue remodelling during decidualization, in tissue repair following menstruation, and additionally in modulating premenstrual inflammatory events. (+info)
Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women.
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BACKGROUND: Studies showed that hormonal fluctuations that occur over the human menstrual cycle affect energy intake and expenditure. However, little is known about the possible effects on body weight regulation that may arise when these cyclic changes are suppressed with hormonal contraceptives. OBJECTIVE: The aim of this study was to examine how a progestational contraceptive drug (depot medroxyprogesterone acetate) affects food intake, resting energy expenditure (REE), and body weight in young women. DESIGN: Twenty normal-weight women were tested in a single-blind, placebo-controlled experiment. Body weight, REE, and 3-d food intake (food provided) were measured in the follicular and luteal phases of 2 menstrual cycles before a single injection of depot medroxyprogesterone or saline solution was administered. Measurements were also taken 4 times after injection: in the luteal and follicular phases of 2 cycles in the placebo group and 2 wk apart (to mimic timing of the menstrual phases) in the drug group. RESULTS: Before injection, the phase of the menstrual cycle affected both energy intake and REE. The study participants consumed more energy (4.3%; P = 0.02) and expended more energy at rest (4.3%; P = 0.0002) in the luteal phase than in the follicular phase. Comparison of pre- and postinjection means showed that treatment with the contraceptive drug had no significant effects on energy intake, REE, or body weight. CONCLUSIONS: This study showed that, although phases of the menstrual cycle affected energy intake and REE, depot medroxyprogesterone acetate did not alter energy intake or expenditure or cause weight gain in young women. (+info)
Increased adhesiveness and internalization of Neisseria gonorrhoeae and changes in the expression of epithelial gonococcal receptors in the Fallopian tube of copper T and Norplant users.
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Interaction of Neisseria gonorrhoeae with the oviductal epithelium in vitro was examined in 2 cm length segments obtained after surgical sterilization from users of copper T intrauterine device (IUD) or Norplant and control women. Segments perfused with N.gonorrhoeae suspensions were incubated from 30 min up to 4 h, fixed, frozen and cut in 6--10 microm sections. Bacteria were detected immunohistochemically with rabbit anti-gonococcal serum followed by light and confocal microscopy. Adhesion and internalization of gonococci by epithelial cells were observed at all incubation times, and both were higher in explants from users of copper T IUD or Norplant implants than controls. The epithelium of controls expressed CD66 and syndecan-1; but CD46 was found in only one out of six cases. The epithelium of copper T IUD users expressed CD66 but not syndecan-1 or CD46. Users of Norplant exhibited expression of CD46, CD66 and syndecan-1. Label was always found along the luminal border of the epithelium. There were more intraepithelial lymphocytes in users of contraceptive methods than in controls. Results indicate that (i) N.gonorrhoeae invade the oviductal epithelium from the first minutes of exposure, (ii) the epithelium is constitutively endowed with two known receptors for the gonococcus, CD66 and syndecan-1, (iii) copper T IUD and Norplant users exhibit higher rates of attachment and internalization of the gonococcus into the oviductal epithelium associated with changes in expression of gonococcal receptors. (+info)