Fertility awareness-based methods of family planning help women identify the days of the menstrual cycle when they are most likely to become pregnant. To prevent pregnancy, women avoid unprotected intercourse on these days. Efficacy of these methods may be improved if the users most likely to engage in unprotected intercourse on fertile days can be identified and counseled. Quantitative and qualitative data from efficacy studies of the Standard Days Method and the TwoDay Method of family planning, in which 928 women each contributed up to 13 cycles of method use, were examined. Multinomial logit analysis was used to compare characteristics of women who occasionally had unprotected intercourse on fertile days with those who consistently used their method correctly. The reasons participants gave for having unprotected intercourse on fertile days were also examined. Only 23% of women had unprotected intercourse on their fertile days in one or more of the cycles they contributed to the study. The method and study site appear to have the most significant effect on correct use. Earning an income was associated with increased odds of unprotected intercourse on fertile days; higher quality of housing was associated with decreased odds. The results confirm the importance of partner cooperation for correct method use. There was no clear profile of clients for whom these family planning methods would be inappropriate. However, programs offering these methods may help couples overcome potential difficulties in correct method use by including male partners and encouraging their participation in counseling sessions.
In the discussion of biologic differences between male and female fertility (April 6 issue),1 Federman states that women are fertile for only 12 hours each month. Although the egg is viable for 12 hours or less, the window of fertility in women is approximately five to six days in each menstrual cycle,24 depending on the presence of estrogenic cervical mucus that maximizes the storage, survival, and transport of sperm until ovulation.4,5 Dr. Stanford rightly calls attention to the elegant estrogen-dominated events that precede ovulation and that favor passage of sperm through the cervix . . .
Bone HealthPharmacological EffectsCOX-2 InhibitorsRisk Factors
The use of cyclooxygenase-2 (COX-2) inhibitors has been demonstrated to not only impair load-induced bone formation but also prevent menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be associated with increased bone mineral density (BMD) in postmenopausal women not using estrogen therapy and, conversely, with decreased BMD in men. The Canadian Multicentre Osteoporosis Study is a longitudinal, randomly selected, population-based community cohort. We present data from men (n=2,004) and postmenopausal women age 65 and older (n=2,776) who underwent a BMD measurement and structured interview in the 5th year of the study. The outcome measure was percent difference in BMD (g/cm(2)). Daily COX-2 inhibitor use was reported by 394 subjects. In men, daily use of COX-2 inhibitors was associated with a lower BMD at all hip sites, with a percent difference of -3.1% [95% confidence interval (CI), -6.0, -0.3] between users and nonusers at total hip. In postmenopausal women not using estrogen replacement therapy, daily COX-2 inhibitor use was associated with higher BMD at most sites [percent +3.0% (95% CI, 0.3, 5.8)]. These effects appeared to be dose-dependent. COX-2 inhibitor use was associated with a lower BMD in men and, on the other hand, with a higher BMD in postmenopausal women not using estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have utility in postmenopausal women if bone-selective analogs can be developed.
The concept of the ovarian cycle as a continuum considers that all types of ovarian activity encountered during the reproductive life are responses to different environmental conditions in order to ensure the health of the woman. During the normal ovulatory cycle, a series of sequential events have to occur in a highly synchronized manner. Fertility awareness is useful in helping women to identify the different stages of their reproductive life cycle. Fertility awareness is also a valuable tool in helping women to identify gynecological disorders. Persistence of irregularities within the mucus patterns and the menstrual cycle should be of concern to women presenting with these problems. These irregularities may be due to obstetrical, endocrine, gynecological or iatrogenic disorders. Insight into early pregnancy complications, ovulatory dysfunction and pelvic inflammatory disease can be ascertained from abnormalities within the menstrual cycle and mucus pattern. Thus, fertility awareness will also enable the recognition and early treatment of several metabolic, endocrine and infectious diseases.
Menstrual CyclePhase Length DistributionOvulation Day EstimationElectronic Fertility Monitors
Fehring RJ et al., 2006·J Obstet Gynecol Neonatal Nurs
To determine variability in the phases of the menstrual cycle among healthy, regularly cycling women.
A prospective descriptive study of a new data set with biological markers to estimate parameters of the menstrual cycles. One hundred forty one healthy women (mean age 29 years) who monitored 3 to 13 menstrual cycles with an electronic fertility monitor and produced 1,060 usable cycles of data. Variability in the length of the menstrual cycle and of the follicular, fertile, and luteal phases, and menses. The estimated day of ovulation and end of the fertile phase was the peak fertility reading on the monitor (i.e., the urinary luteinizing hormone surge). Mean total length was 28.9 days (SD = 3.4) with 95% of the cycles between 22 and 36 days. Intracycle variability of greater than 7 days was observed in 42.5% of the women. Ninety-five percent of the cycles had all 6 days of fertile phase between days 4 and 23, but only 25% of participants had all days of the fertile phase between days 10 and 17. Among regularly cycling women, there is considerable normal variability in the phases of the menstrual cycle. The follicular phase contributes most to this variability.
Amenorrhea is a diagnostic criterion for anorexia nervosa (AN), although menstrual cycles have been found to persist in some women with all the other features of AN. This study sought to determine factors that are associated with amenorrhea in 39 women with current primary spectrum AN. The use of exercise to control weight (odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.3-9.9; P = .02), low novelty seeking scores (OR = 0.7; 95% CI = 0.58-0.94; P = .02), and low systolic blood pressure (OR = 0.9; 95% CI = 0.84-0.99; P = .046) were predictors of amenorrhea independent of body mass index.
Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications. We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects. This was a prospective study. The study was conducted in the Department of Obstetrics and Gynecology. A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)). TPOAb(+) patients group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group. Rates of obstetrical complications in treated and untreated groups were measured. At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7). Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.
With the collaboration of Italian centres providing services on natural family planning, a prospective study collected data on 2755 menstrual cycles of 193 women. A database was constructed using information on the daily characteristics of cervical mucus and episodes of intercourse. Taking the day of peak mucus as a conventional marker of ovulation, the database identified the length (12 days) and location of a 'window' of potential fertility, the highest level of conception probability being confined to the central five to six days. Univariate analysis provided evidence of the impact on fecundability of the woman's age and the basic infertile pattern of a cycle. Several analytical approaches highlighted the relationship between daily mucus characteristics and levels of fecundability
Ethics/PhilosophyHistorical DevelopmentMedical Decision Making
The principle of informed consent, aimed at the lawfulness of health assistance, tends to reflect the concept of autonomy and of decisional autodetermination of the person requiring and requesting medical and/or surgical interventions. This legal formula, over the last few years, has gained not only considerable space but also importance in the doctrinal elaboration and approaches, as well as juridical interpretations, thereby influencing the everyday activities of the medical profession. Informed consent is still the object of continuous explorations, not only asfar as concerns the already confirmed theoretical profile but, instead, the ambiguous practical and consequential aspect. Analysing how the concept and role of consensus was born and developed with the more adequate and reasonable excursions to make it valid and obtain it, it is impossible not to take into consideration, on the one hand, the very ancient philosophical origins and, on the other, the fact that it was conditioned by religion with the moral aspects and the accelerated deontological evolution with pathways parallel to the needs and the progress offered by new forms of treatment and novel biotechnological applications. The principle of consent is a relatively new condition. In fact, already in the times of not only the Egyptian civilisation, but also the Greek and Roman, documents have been found which show how the doctor's intervention had, in some way, first to be approved by the patient. Plato (law IV) had already foreseen the problems, the procedures and the modes of information which are, in synthesis, at the root of the principles of the present formula of informed consent and correlated the practice of the information and consensus with the quality and social position of the patient. The only guarantee that the patient might have, derived from a fundamental principle "in disease, focus on two aims, to improve and not to cause damage". A figure can be recognised, in the Hippocratic physician, that cared about the patient's suffering, but never neglected looking after his own outcome, endeavouring to avoid becoming involved in lack of success and death of a patient. The concept of consensus is inexistent, albeit, there is an awareness of the presence of precautious and preventive information. In the behaviour of doctors, in ancient times, it is not difficult to recognize the true motives and the real reasons that, already in those days, give rise to the necessary "defensive medicine" particularly as far as concerns the social status of the patient. Already from the early origins, continuing the Hippocratic tradition, the relationship between doctor and patient was consolidated, based upon two very definite criteria, represented, on the one hand, by the professional duty of the physician to do what is bestfor the patient and, on the other, the duty of the patient to completely accept the physician's decisions and intervention. The Hippocratic physician respected a principle of professional responsibility which was more religious and of a moral type, but, from a legal point of view, very weak inasmuch as it depended upon regulations elaborated by human beings. The conviction and certainty that the physician acted, in the interest of his patient's well-being, has been passed down over the centuries endowing the physician with moral authority and a kind of legal impunity, conditions which corresponded, in an almost reflection-likefashion, with the duty of obedience and subjection, on the part of the patient. Christianity was grafted into this consolidated vision of the sacral character of medicine and medical practice, which did not substantially change the Hippocratic type of ethical behaviour. Non only the population but also the Christian physician was aware of the religious importance of his intense activity as a mission and compared to a special kind of priesthood in safe-guarding health, considered as a gift of God. Therefore, invested with this authority which derived from his professional role and from his very work, he felt it his duty to guide the patient, deciding and for him. The patient is an ignorant person who does not have the knowledge, the intellectual capacity or moral authority to oppose or disagree with the wishes and decisions of the physician who, instead, on account of his doctrine, knows exactly what is goodfor him. In this regard, if we were to speak of consensus concerning the physician's intervention, he would be considered useless in as much as obvious and understood when seeking help. The attitude of the patient towards the physician has always tended to one of strong faith and characterized by psychological subjection borne out by traditions thousands of years old. A patient who was sick, again, as an attitude of respect and gratitude, followed the treatment but never asked for any explanations regarding the therapeutic effects and the physician refrained from taking any initiative to inform the patient or his/her family. Each phenomenon, therefore, has a precise origin, a well-defined history and when its importance tends to significantly condition the activities concerning Man, a desire emerges to learn the origin and the history. As is well known, a trial commenced in Nuremberg, on December 19, 1946, of Nazi doctors and a code was defined in which the judges, all Americans, clearly emphasized a view of medical science should never transform or consider human beings as an instrument to be employed for scientific purposes. In actual fact, documents exist providing evidence that a few decades before the drawing up of the Nuremberg Code, the need had been expressed, in Germany itself to somehow make medical interventions and actions legal by means of the use and practice of consensus. The moral and ethical principles in those documents, even if not available as bibliographic references in the English literature, certainly merit, from a historical viewpoint to be considered as conceptual elements and doctrinal and socio-cultural products, even if at that time, of little practical importance, which belong to the European culture and, in particular, and almost paradoxically, in the light of what happened, to the German culture. The United States of America is held to be the country of origin of informed consent, the initial aim of which was make sure that the correct dignity of the patient's independence be reserved at the time of decision making and choice of medical options. Reports on this topic, in fact, first appeared in the USA, at the beginning of the 18th Century, with problems focusing on and limited to only the simple rights of the patient in giving his/her approval of the health intervention later to be conceptually developed, along the lines of an itinerary with, at intervals, famous legal actions, until in the 20th Century, informed consent was reached, a criterion that, as is well known, foresees and includes not only the important and fundamental autonomy of the patient to decide, which stems ones personal rights, but also the essential objective element, which is, information. The expression informed consent has simply been transposed in Italian and roughly translated in an ambiguous fashion into "consenso informato" when, on the contrary, it should be referred to as "informazione per il consenso" "information for consensus" not only to respect the concept but, surely, for a more correct deciphering and a more precise interpretation related to the numerous concepts it presupposes and implies. Information and consent may be compared to the two sides of the same coin. These are the two important pillars that coincide and are joined giving weight to the medical responsibility, as far as concerns consent on the one hand, having obtained consent,following correct and sincere information interpreted and deciphered as an important phase and an essential indicator of correct, scrupulous medico-professional procedure and, on the other, the consensus itself conceived as a duty aiming at the maximum respect of the rights to autodetermination, independence and autonomy of the patient, as a person. At the beginning of the Nineties, as we have seen, we were made aware of a series of legal actions regarding medical responsibility which was greatly conditioned by the Anglosaxon influence which initially induced many Italian magistrates and forensic physicians to adopt an extremely rigid attitude with no attempt to comply, in any way, with the culture and traditions of our country and our tradition which has always been inspired by good common sense, both medical and human. The American experience has been very rapidly adopted, by some, without a profound, complete and necessary historical and evolutional analysis aimed at those intertwined principles that have been motifs that have gradually led to the legal references in those emblematic cases referred to, the conclusions of which continue to attract a great deal of attention. In Italy, the legal and doctrinal evolution of informed consent, even if following a little more rapidly the traces, steps, problems and interpretations of the various aspects drawn up, characterized and applied in the United States, has not only occurred at a later time, but, despite reaching the same meaningful objectives, the same considerations, the same importance, and, unfortunately, the same inconveniences, has had quite different aims, approaches and articulations. In this respect, it is enough to focus attention on the different cultural traditions and religious routes, on the different doctrinal background, the particular historical origins and the individual legal aspects, all extremely different one from the other. (ABSTRACT TRUNCATED)
AndrologyDNA IntegrityChemotherapy Effects on FertilityChromatin Analysis
While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood. Semen and serum from 22 patients treated for testicular cancer were analysed preand post-chemotherapy. Besides routine semen analysis, sperm samples were evaluated by computerized karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage). Serum FSH, LH and testosterone concentrations were measured. Ejaculate volume decreased post-chemotherapy (P<0.05). External sperm characteristics (CKIA morphometry) and sperm counts did not deteriorate after chemotherapy. An improvement in DNA condensation was assessed after chemotherapy (37 versus 50% and 47.5 versus 63.7% for CMA3 and CKIA respectively; both P<0.005); yet a high percentage of TUNEL-positive sperm was found in the samples (21 versus 25% for preand post-chemotherapy samples respectively). These values were significantly higher than those of a convenience sample of normozoospermic males attending pre-IVF screening. Serum FSH and LH (IU/l) increased after chemotherapy compared with pretreatment levels (8.1 versus 16.7 and 4.5 vs 6.8; both P<0.05, respectively). Despite the improvement in sperm chromatin packaging after chemotherapy, an abnormally high percentage of DNA-damaged sperm was found in these samples. As sperm quality does not reach normal levels after treatment, it remains difficult to outline the best strategy and guidance concerning fertility potential of testicular cancer patients.
Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of disparity were examined. Retrospective cohort study. University-based ART program. PATIENT(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate. RESULT(S): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98). CONCLUSION(S): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success, regardless of race. The persistence of racial differences in an equal-access-to-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women.
Effective tubal transport of ova, sperm and embryos is a prerequisite for successful spontaneous pregnancy. Although there is much yet to be discovered about the mechanisms involved, it is evident that tubal transit is a far more complicated process than initially thought. Propulsion of gametes and embryos is achieved by complex interaction between muscle contractions, ciliary activity and the flow of tubal secretions. Evidence is accumulating of the important and possibly pre-eminent role of ciliary motion in this process; and this review describes current knowledge about ciliary activity and its physiological regulation. There is also a description of the effects on ciliary function of cigarette smoking and various pathological states, including endometriosis and microbial infection, with consideration given as to how altered ciliary activity may impact upon fertility.
Research MethodologyQuality of Life AssessmentCanadian Multicentre Osteoporosis Study
Limited information exists regarding the natural progression of health-related quality of life (HRQOL) in the general population, as most research has been cross-sectional or has followed populations with specific medical conditions. Such norms are important to establish, because the effect of any intervention may be confounded by changes due to the natural progression of HRQOL over time. Participants were randomly selected from 9 Canadian cities and surrounding rural areas. Changes in the eight domains and 2 summary component scores of the Medical Outcomes Study 36-item short form (SF-36) were examined over a 5 year period (1996/1997-2001/2002). Mean changes were calculated for men and women within 10 year age categories. Multiple imputation was used to adjust for potential selection bias due to missing data. The baseline sample included 6539 women and 2884 men. Loss to follow-up was 17% for women and 23% for men. Mean changes tended to be small, but there was an overall trend towards decreasing HRQOL over time. Changes were more pronounced in the older age groups and in the physically oriented domains. Younger age groups tended towards small mean improvements, particularly in the mentally oriented domains. Large standard errors suggest that on an individual level, large improvements in some participants are balanced by large declines in others. In general, the HRQOL of Canadians appears relatively stable over a 5 year period. However, care should be taken when assessing HRQOL longitudinally in certain age or gender groups, as changes associated with an intervention can potentially be confounded by the natural progression of HRQOL.
Prior studies have suggested that oral contraceptives (OCs) may be associated with an increased fracture risk. However, the previous studies have only performed a limited adjustment for other potential risk factors. Subjects and methodsAll women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was use of OCs between January 1, 1996, and December 31, 2000. Adjustments were made for use of other drugs, pregnancy, prior fracture, other diseases and social variables. In the unadjusted analysis, use of OCs in low dose was associated with a small increase in overall fracture risk. However, upon adjustment, no increase in fracture risk could be demonstrated in any age or dose group. Oral contraceptives are not associated with an increase or a decrease in fracture risk. Any change in fracture risk may be due to confounders.
Gonzales C et al., 2006·Journal of ethnopharmacology
Lepidium meyenii (Brassicaceae), known as Maca, is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m above sea level in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The study aimed to test the hypothesis that different ecotypes of Maca (Red, Yellow and Black) after short-term (7 days) and long-term (42 days) treatment affects differentially spermatogenesis adult rats. After 7 days of treatment with Yellow and Red Maca, the length of stage VIII was increased (P<0.05), whereas with Black Maca stages II-VI and VIII were increased (P<0.05). Daily sperm production (DSP) was increased in the group treated with Black Maca compared with control values (P<0.05). Red or Yellow Maca did not alter DSP and epididymal sperm motility was not affected by treatment with any ecotype of Maca. After 42 days of treatment, Black Maca was the only ecotype that enhanced DSP (P<0.05). Moreover, Black Maca was the only that increased epididymal sperm motility (P<0.05). In relation to the control group, Red Maca did not affect testicular and epididymal weight nor epididymal sperm motility and sperm count; however, prostate weight was reduced (P<0.05). Black or Yellow Maca did not affect prostate weight. In conclusion, there were differences in the biological response of the three ecotypes of Maca (Yellow, Red and Black). Black Maca appeared to have more beneficial effect on sperm counts and epididymal sperm motility.
Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.
Increased menstrual bleeding and pain are the primary side effects that lead to early removal of the copper intrauterine device (IUD). Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) are proven treatments for such IUD-induced problems, but their effect on early IUD removal is unknown. A total of 2019 first-time IUD users were recruited in Chile for this double-blind, randomized, placebo-controlled trial. Half of the participants were given ibuprofen and instructions to take 1200 mg daily during menses (for up to 5 days each cycle) for the first 6 months of IUD use. The other half were asked to take an identical appearing placebo in the same manner. The primary outcome was IUD removal within 12 months of insertion. A total of 1011 and 1008 women were randomly assigned to ibuprofen and placebo, respectively. During 12 months of observation, 190 had the device removed because of dysmenorrhoea and/or 85 in the placebo group and 105 in the ibuprofen group. For ibuprofen users, the hazard ratio for removal for these IUD-induced side effects was 1.0 and 1.2 at 6 and 12 months, respectively (both not significant). Although increased menstrual bleeding and pain are common reasons for early IUD removal, prophylactic use of ibuprofen, at the dosage used here, does not reduce removal rates.
This systematic review examines evidence evaluating whether women with headaches who use combined oral contraceptives (COCs) have a greater risk of stroke than women with headaches who do not use COCs. We searched MEDLINE for articles published from 1966 through March 2005 relevant to headaches and COC use as risk factors for stroke. Of the 79 articles identified, nine met our selection criteria (eight reports of six observational studies plus one meta-analysis). All studies reported specifically on migraine headaches. Evidence from six case-control studies suggested that COC users with a history of migraine were two to four times as likely to have an ischemic stroke as nonusers with a history of migraine. The odds ratios for ischemic stroke ranged from 6 to almost 14 for COC users with migraine compared with nonusers without migraine. The three studies that provided evidence on hemorrhagic stroke reported low or no risk associated with migraine or with COC use.
Estrogen exposure is a major determinant of the risk of breast cancer. This article reviews how genotoxic, mutagenic metabolites of estrogen and stimulation of tissue growth by the hormone participate in the pathogenesis of breast cancer.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2005. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Fertility AwarenessScientific EvidenceNatural Family PlanningResearch Overview
Assessing the psychological acceptability of technologies designed to assist couples in achieving pregnancy is complex. The current study developed measures relating to the impact of one such technology on 52 couples' relationships, their feelings relating to pregnancy status and their feelings about the technology itself. Pregnancy status and daily logs of sexual activity were recorded for four menstrual cycles, in addition to the completion of acceptability questionnaires. Baseline acceptability measures were more favorable among couples eventually achieving pregnancy. For couples not becoming pregnant, acceptability declined over time and relationships became more strained. Behavioral data clearly indicated a "targeting" and focusing of sexual activity in response to the information displayed by the monitor. Expectations of success, couple disagreements about prior failure and partner communication patterns appear to be related to pregnancy success when using such technology.
Body LiteracyAdolescent Sexual Health ProgramsTeen ProgramsAbstinence Education Outcomes
Open Access
Urgent measures are required to stop the increase in the frequency of pregnancies and sexually transmitted diseases among teenagers. A means of facing this problem is promoting sexual abstinence among youngsters. There are studies that confirm the efficacy of this approach. To show the results of the application of a holistic sexuality program (TeenSTAR) among Chilean teenagers. Students attending basic or high school were divided into a control or study group. The control group (342 students) received the usual education on sexuality given by their schools and the study group (398 students) participated in twelve TeenSTAR sessions lasting 1.5 hours each, given by a trained professor. Assessment of achievements was made using an anonymous questionnaire answered at the start and end of the program. The rates of sexual initiation among control and study groups were 15 and 6.5%, respectively. Among sexually active students, 20% of those in the study group and 9% of those in the control group discontinued sexual activity. A higher proportion of students in the TeenSTAR program retarded their sexual initiation or discontinued sexual activity and found more reasons to maintain sexual abstinence than control students.
Nagle CA et al., 2005·General and comparative endocrinology
The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.
Contraception/ComparisonSide EffectsDepression and MoodHormonal Influences
Although there have been numerous studies investigating the relationship between the use of oral contraceptives and depressive symptoms, they have differed widely in both their methods and findings. A particular problem is determining and quantifying depression. The authors onducted a pilot study using well validated depression rating scales. (non-author abstract)
To investigate the molecular mechanism for declining sperm motility in older men. Retrospective and prospective study. University-based andrology unit. PATIENT(S): Semen was collected from 2,111 patients and sperm donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, sperm concentration, ejaculate volume, sperm motility (including velocity average path, velocity straight line, velocity curvilinear, linearity, and lateral head displacement), normal sperm morphology, percentage of abnormally blue-stained flagella, and total and free T, FSH, and LH concentrations were analyzed. In addition, the zinc concentration in the seminal fluid, flagella, and the whole spermatozoa was measured by means of atomic absorption spectrometry. RESULT(S): Patient age correlated negatively with T concentration and sperm motility, including velocity, but positively with the percentage of abnormally stained flagella and the flagellar zinc. Whereas the percentage of abnormally stained flagella correlated negatively with motility and sperm velocity, there was a positive relationship with the flagellar zinc content. Flagellar zinc content was negatively correlated with motility. Testosterone showed a positive relationship with motility and sperm concentration. CONCLUSION(S): Because the epididymis is functionally T-dependent, our data suggest that the removal of zinc from the outer dense fibers during epididymal sperm maturation is affected in aging men, which in turn will result in decreased sperm motility.
A meta-analysis was performed on 11 cohort studies of Assisted Reproductive Technologies (ART) and subsequent childhood cancer, published up to February 2005, which reported comparable, nonoverlapping data, and then restricted to eight studies which presented a similar research design. The overall Standardised Incidence Ratio was 1.33 (95% CI 0.62-2.85), and 0.77 (95% CI 0.41-1.42) when the analysis was restricted to eight studies. No evidence of publication bias was observed for the overall analysis. The data are consistent with a lack of increase in risk of childhood cancer, though the amount of data on ART and cancer is still limited; larger multicentric studies as well as a pooled analysis on the available data are warranted.
Perimenopause/MenopauseReproductive Endocrinology
Open Access
Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STATS, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.
General OB/GYNRisk FactorsCancer RiskSmoking and Cofactors
Cervical cancer is a complex and multifactorial disease. Although there are substantial data supporting the causative role of persistent human papillomavirus (HPV) infection in the development of cervical cancer, the complete course of the disease has never been completely understood. Several risk cofactors have been suggested with controversial results. Portugal has the highest incidence of squamous cell carcinoma (SCC) within western Europe and there are no known studies regarding the role of cofactors in SCC. The aim of our study was to evaluate the role of smoking, sexual behaviour, reproductive and contraceptive history, in the time-to-onset (TTO) of severe cervical lesions (HGSIL/SCC) in the Portuguese population. We verified that age of first sexual intercourse under 18 years (odds ratio (OR) 2.8), pregnancy (OR 2.9), first pregnancy under 21 years (2.6), number of pregnancies (OR 2.3-5.4) and parity (OR 1.9-5.7) are risk factors in the development of cervical neoplasia. Smoke exposure index (SEI) was significantly different (P=0.002) between cases and controls. Our results regarding time-to-onset demonstrate that smoking (P<0.001, log rank test), number of sexual partners (P<0.001, log rank test) and use of oral contraceptives (P<0.001, log rank test) are important determinants in the earlier onset of severe cervical lesions. Using this approach, our findings may help to clarify the role of smoking and other cofactors in the persistence and progression of cervical lesions.
Contraception/ComparisonBreast Cancer RiskFamily History and Risk FactorsCancer Epidemiology
Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrollment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73-1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (p(trend)=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47-1.19, p(trend)=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer.
Fertility AwarenessElectronic Hormonal Fertility MonitorReturn of FertilityBreastfeeding Protocols
A protocol was developed and evaluated for nonovulating breastfeeding women to determine potential fertility with an electronic hormonal fertility monitor. The amount of required abstinence (i.e., days of potential fertility) through the first menstrual cycle indicated by the fertility monitor was significantly lower (17% of the total days) compared with the amount of abstinence (50% of the total days) indicated by the self-observation of cervical mucus.
Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS). To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners. One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records. The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity. The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS.
Fertility AwarenessBasal Body TemperatureOvulation DetectionClinical Counseling
Advanced practice nurses in primary care settings are often asked to give appropriate advice to couples seeking pregnancy. This article examines the issue of basal body temperature (BBT), a time-honored way to establish the presence of ovulatory cycles, and asks if BBT is an outdated recommendation. The article also reviews the benefits and limitations of recommending BBT to couples seeking pregnancy in light of recent fecundity research.
Contraception/ComparisonBreast Cancer RiskBreast Cancer GeneticsLong-term Health Outcomes
Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.
Bone HealthQuality of LifePopulation-Based StudiesHealth Utility Index
The objective of this research was to determine the relative decrement in health-related quality of life, as measured by the health utilities index mark 3 (HUI3), in osteoporosis compared to other chronic medical conditions. The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey (NPHS). The Canadian Multicentre Osteoporosis Study (CaMos) is a national population-based study in which regional participants were randomly recruited, regardless of presence of osteoporosis. We analyzed data from participants aged > or = 65 years who completed a baseline HUI3 questionnaire and provided information on their medical history (n=3,750). We determined the ageand gender-adjusted mean decrement in HUI3 for several chronic medical conditions, including osteoporosis. The mean changes in HUI3 adjusted for age and gender (with 95% confidence intervals) arthritis -0.10 (-0.11, -0.09), chronic obstructive pulmonary disease (COPD) -0.07 (-0.09, -0.05), diabetes mellitus -0.05 (-0.08, -0.03), heart disease -0.06 (-0.08, -0.04), hypertension -0.02 (-0.03, -0.01), and osteoporosis -0.08 (-0.11, -0.06), respectively (model r2=0.17; P<0.0001). These findings were comparable to those observed in the NPHS, with the exception of osteoporosis, which had not been previously studied in this fashion. The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions, such as arthritis, COPD, diabetes mellitus or heart disease.
Contraception/ComparisonGastrointestinal DiseaseInflammatory Bowel DiseaseLong-term Health Outcomes
García Rodríguez LA et al., 2005·Aliment Pharmacol Ther
The aetiology of inflammatory bowel disease remains largely unknown. We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.
To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.
A prospective cohort of 93,725 postmenopausal women.
Forty Women's Health Initiative (WHI) clinical centers across the United States. PATIENT(S): Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire. RESULT(S): The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users. CONCLUSION(S): This study does not support the idea that past OC use protects against later fracture.
The purpose of this review is to put into a useful clinical context the changing over time of basic ovarian-pituitary-hypothalamic relationships during perimenopause. "Perimenopause" means changes in ovarian hormones, feedback relationships, and clinical experiences beginning in women ages 35-50 with regular flow and ending 1 yr after the final menstrual flow. A key observation must be explained--estradiol levels are increased in perimenopause. Inhibin B levels are lower and activin may be higher in midlife, menstruating women. These changes probably cause higher follicular phase FSH levels--"endogenous ovarian hyperstimulation" results. The positive estradiol feedback on LH is also disturbed--midcycle LH peaks and mid-luteal slow-frequency, high-amplitude LH pulses are less frequent. In addition to higher levels, estradiol receptors may increase in tissues of symptomatic women. Despite hyperstimulation of follicles, progesterone levels and luteal phase lengths are paradoxically decreased--reasons probably include LH peak disruptions and estrogen-stimulated greater corticotrophin-mediated reproductive suppression. In summary, disturbed feedback relationships causing higher and unpredictable estrogen and lower progesterone levels occur throughout perimenopause, especially during regular cycles. Prospective, population-based research is needed to systematically relate these feedback hormonal changes to clinical characteristics and to allow a diagnosis of perimenopause in regularly cycling midlife women.
The objective of the present paper is to review the main results of recent European cycle databases on ovulation detection and determination of the fertile window performed by the women themselves. The ongoing German Long-term Cycle Database currently comprises 32788 prospectively collected cycle charts of 1551 women, the I European Cycle Database (10 countries) 1328 women/19048 cycles, the II European Cycle Database (six countries) 782 women/6724 cycles, and the World Health Organization Database (one European country) 234 women/2808 cycles. The women record cycle parameters (cervical mucus changes, temperature rise, etc.), family planning intention and sexual behavior. With the symptothermal method of natural family planning it has become possible to determine the fertile window in order to avoid pregnancy with a method effectiveness of 0.3%. According to a small sub-study, the ovulation time observed by the women themselves correlates closely with ovulation detected by ultrasound and measurement of luteinizing hormone (correlation within 1 day in 89% of the 62 cycles). Fertility awareness methods can be integrated into the management of sub-fertility. They seem to shorten the time to pregnancy. Self-observation of the fertile window puts women into a position to develop a high level of reproductive competence that could be used much more in different areas than is currently the case.
Menstrual CycleUltrastructureScanning Electron MicroscopyCervical Mucus Patterns
Two main types of cervical mucus have been described oestrogenic and progestative. Each category shows diverse morphological and functional features from the reproductive point of view. Traditionally, this change has been approached by analysing morphological patterns. In fact, a mesh model has been described for cervical mucus, structurally composed of fibrillar subunits with a parallel orientation, together with another model in a characteristic network shape with canalicular units, but the real model is not clear. The objective of our work was to study the different morphological structures of the mucus, as related to the day of follicular rupture (considered as day 0) determined by ultrasound. Cervical mucus samples were obtained from the cervical canal with an ASPIRETTEtrade mark from day -4 to day +1 of the menstrual cycle. Samples were fixed and dried by critical point. The ultrastructure was examined with scanning electron microscopy. The presence of three types of oestrogenic and one type of progestative cervical mucus was confirmed in this period. Our paper shows different types of ultrastructure in the oestrogenic mucus in relation to ovulation, which would help to understand the interaction between male gametes and cervical mucus in migration through the female genital tract.
This review summarizes the numerous observations published in recent years which have shown that one of the most significant of melatonin's pleiotropic effects is the regulation of the immune system. The overview summarizes the immune effects of pinealectomy and the association between rhythmic melatonin production and adjustments in the immune system as markers of melatonin's immunomodulatory actions. The effects of both in vivo and in vitromelatonin administration on non-specific, humoral, and cellular immune responses as well as on cellular proliferation and immune mediator production are presented. One of the main features that distinguishes melatonin from the classical hormones is its synthesis by a number of non-endocrine extrapineal organs, including the immune system. Herein, we summarize the presence of immune system-synthesized melatonin, its direct immunomodulatory effects on cytokine production, and its masking effects on exogenous melatonin action. The mechanisms of action of melatonin in the immune system are also discussed, focusing attention on the presence of membrane and nuclear receptors and the characterization of several physiological roles mediated by some receptor analogs in immune cells. The review focuses on melatonin's actions in several immune pathologies including infection, inflammation, and autoimmunity together with the relation between melatonin, immunity, and cancer.
Farquhar CM et al., 2005·BJOG : an international journal of obstetrics and gynaecology
To determine whether or not hysterectomy leads to an earlier onset of the menopause. A prospective cohort study. Gynaecology service of large urban hospital. Premenopausal women with and without hysterectomy. Multivariate survival analysis techniques were used to adjust for differences in initial follicle stimulating hormone (FSH) levels, body mass index, smoking and unilateral oophorectomy between the groups. FSH levels were measured for five years following hysterectomy and compared with the comparison group. Menopause was defined as a single FSH measurement of at least 40 IU/L. Two hundred and fifty-seven women undergoing hysterectomy were compared with 259 women who had not undergone a hysterectomy. Fifty-three women (20.6%) in the hysterectomy group and 19 women (7.3%) in the comparison group reached menopause over the five years of the study. Women in the hysterectomy group with a pre-operative FSH <10 IU/L reached menopause 3.7 years (95% CI 1.5-6.0 years) earlier than women in the comparison group independent of BMI, smoking and unilateral oophorectomy. Twenty-eight women in the hysterectomy group had unilateral oophorectomy and 10 (35.7%) of these women reached menopause over the five years of follow up. Women in the hysterectomy group with unilateral oophorectomy reached menopause 4.4 years (95% CI 0.6, 7.9 years) earlier than women with both ovaries in the hysterectomy group independent of baseline FSH, BMI and smoking. Hysterectomy is associated with an earlier onset of menopause. Hysterectomy with unilateral oophorectomy is associated with an even earlier onset of the menopause in this study.
Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins.
Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively).
Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.
To develop a new method for estimating the effectiveness of emergency contraception (EC) by using information about previous menstrual cycle length, accounting for the variation in the day of ovulation within the menstrual cycle, and comparing the validity of the new and previous methods. METHOD(S): Secondary analysis of a data set with a biological marker of ovulation and its distribution in the cycle. Based on a sample of cycles with known length and a known biological marker of ovulation, we simulated trials of predetermined EC effectiveness and then calculated estimates of EC effectiveness based on old and new methods. RESULT(S): Under some conditions, all methods produced biased estimates of effectiveness with simulated trials, especially when the actual effectiveness was low. The systematic bias was minimized with the new method. The new method was robust with regard to the distribution of the day of intercourse in women presenting for EC. CONCLUSION(S): Future studies of EC effectiveness should consider both the uncertainty in predicting the day of ovulation and previous cycle length. Our estimates of daily fecundity should be replicated with other data sets.
Progesterone products are available in prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design, the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase), whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing the cream to oral capsules (median AUC(0-24) 12.5 ng x h/mL vs 10.5 ng x h/mL, respectively; P = .81). In light of the potential risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available OTC.
Ruiz-Luna AC et al., 2005·Reproductive biology and endocrinology : RB&E
Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Adult female Balb/C mice were divided at i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility.
Empson M et al., 2005·The Cochrane database of systematic reviews
A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks. To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL. We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999. Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL. Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999. Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials. Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes. AUTHORS' Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.
Menstrual CycleRespiratory FunctionEstradiol and ProgesteroneRepeated Measures
Catherine J Bacon et al., 2005·Respir Physiol Neurobiol
To determine whether lung transfer factor for carbon monoxide (T(L(CO))) alters during menstrual phase and if steroid hormone levels relate to these changes, T(L(CO)) and T(L(CO)) adjusted for both alveolar volume (T(L)/V(A)) and haemoglobin concentration, were measured at five predefined and hormonally confirmed menstrual phases in 13 women. No difference between phases was observed in T(L(CO)) or adjusted values. Moreover, there was no association between the maximal change in oestradiol, progesterone, progesterone ratio and the change in T(L(CO)) measured at the same time. When the first five chronological measurements, regardless of the menstrual phase at which they were measured, were analysed, T(L(CO)) changed significantly (p<0.05) with a maximal change between the first and fourth test (-2.69+/-2.53, 95% confidence interval). Although these results indicate that the first in a series of T(L(CO)) measurements may be higher, we found neither menstrual cycle phase nor ovarian hormone-related changes in T(L(CO)), and conclude that its adjustment for menstrual phase may not be necessary.