Is the operative delivery rate in low-risk women dependent on the level of birth care? A randomised controlled trial.

OBJECTIVE: To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital. DESIGN: Randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway. POPULATION: A total of 1111 women assessed to be at low risk at onset of spontaneous labour. METHODS: Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit. MAIN OUTCOME MEASURES: Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score <7 at 5 minutes, metabolic acidosis and transfer to neonatal intensive care unit. RESULTS: There were no significant differences in total operative deliveries between the three units: 16.3% in the midwife-led unit; 18.0% in the normal unit; and 18.8% in the special unit. There were no significant differences in postpartum haemorrhage, sphincter injuries or in neonatal outcomes. There were statistically significant differences in augmentation (midwife-led unit versus normal unit RR 0.73, 95% CI 0.59-0.89; midwife-led unit versus special unit RR 0.69, 95% CI 0.56-0.86), in epidural analgesia (midwife-led unit versus normal unit RR 0.68, 95% CI 0.52-0.90; midwife-led unit versus special unit RR 0.64, 95% CI 0.47-0.86) and in acupuncture (midwife-led unit versus normal unit RR 1.45, 95% CI 1.25-1.69; midwife-led unit versus special unit RR 1.45, 95% CI 1.22-1.73). CONCLUSIONS: The level of birth care does not significantly affect the rate of operative deliveries in low-risk women without any expressed preference for level of birth care.

Prevalence of Cryptosporidium spp. and Giardia spp. in five marine mammal species.

Cryptosporidium spp. and Giardia spp. are protozoan parasites that are often associated with severe diarrheal disease in a variety of mammals. Although these parasites have been extensively studied in terrestrial ecosystems, little is known about either parasite in the marine environment. Therefore, the objective of this study was to determine the prevalence of both Cryptosporidium spp. and Giardia spp. in 5 marine mammal species. Fecal samples were collected from 39 bowhead whales (Balaena mysticetus), 49 North Atlantic right whales (Eubalaena glacialis), 31 ringed seals (Phoca hispida), 22 bearded seals (Erignathus barbatus), and 18 beluga whales (Delphinapterus leucas) between 1998 and 2003. Using an immunofluorescent assay, parasites were detected in the feces of bowhead whales, right whales, and ringed seals, while neither parasite was detected in samples from bearded seals or beluga whales. Overall, prevalences were highest in ringed seals (Cryptosporidium spp., 22.6%; Giardia spp., 64.5%) and right whales (Cryptosporidium spp., 24.5%; Giardia spp., 71.4%) and lowest in bowhead whales (Cryptosporidium spp., 5.1%; Giardia spp., 33.3%). To our knowledge, this is the first report of Cryptosporidium spp. and Giardia spp. in either whale species and of Cryptosporidium spp. in the ringed seal.

Effects of pond water, sediment and sediment extract samples from New Hampshire, USA on early Xenopus development and metamorphosis: comparison to native species.

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine.

Campylobacter-induced enteritis and diarrhea in captive cotton-top tamarins (Saguinus oedipus) during the first year of life.

A prospective study of 43 cotton-top tamarins, from infancy to 6 to 17 months of age, was conducted to determine the epidemiology of Campylobacter spp. infection. Nine infants followed for one year in an isolation unit, where attendants wore protective clothing, did not become infected. In the main facility where 32 of 34 animals had repeated infections with C. coli, 6% of the infections developed initially in incubators, 66% in the nursery room, and 28% after transfer to the main colony. Fifteen of these tamarins also were infected with C. jejuni. Twenty percent of the infections developed initially in the nursery room and 80% in the colony. Polyacrylamide gel electrophoresis analysis of C. jejuni cultures revealed multiple reinfections with different strains. Both types of infections were most prevalent between 3 and 9 months of age. Campylobacterjejuni infection developed most frequently between April and June and C. coli infection developed between October and December. In the nursery, diarrhea developed most frequently at times when there was no infection with Campylobacter spp. Forty percent of animals with diarrhea in the nursery had C. coli and none had C. jejuni, whereas, in the colony, 49% had C. jejuni and 11% had C. coli infections. There was no association between these infections and diet or idiopathic colitis.

A review of chemically-induced alterations in thyroid and vitamin A status from field studies of wildlife and fish.

This paper reviews 22 published field studies that have found an association between exposure to environmental contaminants and alterations in thyroid gland structure, circulating thyroid hormones and vitamin A (retinoid) status in free-ranging populations of wildlife and fish. Vitamin A and thyroid hormones play critical roles during development, growth and function 'throughout life. Studies of captive wildlife and laboratory studies support a relationship between alterations in thyroid hormones and vitamin A status and exposure to dioxins, furans, and planar polychlorinated biphenyls, which bind to the aryl hydrocarbon receptor. Some studies have found adverse health effects in wildlife associated with exposure to polyhalogenated aromatic hydrocarbons and altered thyroid and retinoid status including: decreased reproductive success, immune system changes, dermatologic abnormalities and developmental deformities. A direct causal relationship between these effects and thyroid and retinoid changes has not been demonstrated. Field researchers studying the responses to these synthetic chemicals in wildlife and fish should include measurement of thyroid hormones and retinoids and histological examination of the thyroid gland in their study design as biomarkers of exposure to these chemicals in the environment.

Omitting the first oral contraceptive pills of the cycle does not automatically lead to ovulation.

OBJECTIVE: Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation. STUDY DESIGN: Ninety-nine women, randomly assigned to 1 of 3 treatments of combined oral contraceptives, completed the study. Treatments contained ethinyl estradiol and either monophasic gestodene, triphasic gestodene, or monophasic desogestrel. Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol, progesterone, and follicle-stimulating hormone over 1 normal cycle (study period 1) and 1 cycle after an extended pill-free interval of 10 days (study period 2). RESULTS: None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations. However, follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery, and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation. During study period 2 we found follicles of >18 mm in 24%, 24%, and 40% of the monophasic gestodene, triphasic gestodene, and monophasic desogestrel groups, respectively. CONCLUSIONS: Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle. Although this creates the prerequisite for ovulation, normal ovulation did not occur when pill omissions were limited to only 3 days.

PIP: The hypothesis that omission of the first three pills of the oral contraceptive (OC) cycle leads to ovulation by extending further the pill-free period was investigated in 107 healthy women 18-35 years of age recruited from family planning programs in Finland, the Netherlands, and Belgium. Study participants were randomly allocated to one of the following treatment groups: 1) monophasic gestodene--75 mcg of gestodene and 30 mcg of ethinyl estradiol; 2) triphasic gestodene--6 days of 50 mcg gestodene and 30 mcg ethinyl estradiol, 5 days of 70 mcg gestodene and 40 mcg ethinyl estradiol, and 10 days of 100 mcg gestodene and 30 mcg ethinyl estradiol; or 3) monophasic desogestrel--150 mcg desogestrel and 20 mcg ethinyl estradiol. Noncompliance with OC taking was simulated by extending the pill-free period from 7 to 10 days. During or after the extended pill-free interval, follicular growth exceeding 18 mm occurred in 24% of women in the monophasic gestodene group, 24% in the triphasic gestodene group, and 40% in the monophasic desogestrel group. Follicle-stimulating hormone reached a maximum serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery. No normal ovulation was observed after either a 7- or 10-day pill-free period as evaluated by ultrasonography of follicles and serum progesterone assays. Since normal ovulation did not occur when pill omissions were limited to 3 days, OC users who forget to take these three tablets can be safely advised to start the pill cycle on day 11.

Environmental neurotoxic effects: the search for new protocols in functional teratology.

Large quantities of a number of man-made chemicals with the potential to disrupt the developing endocrine and nervous systems in wildlife and humans have been released into the environment. These chemicals are particularly damaging during the embryonic, fetal, and early postnatal periods because they resemble or interfere with the hormones, neurotransmitters, growth factors, and other signaling substances that normally control development. The effects are in many cases irreversible and often are expressed as changes in function rather than as obvious birth defects or clinical diseases. Functional changes pose challenges in documenting the extent of the lesion, especially in the case of neuroendocrinological damage. In the past decade, researchers have added new dimensions to their research strategies in order to compensate for these difficulties. The new approaches reveal more about the extent of the distribution of and exposure to chemicals that interfere with the endocrine and nervous systems and strengthen the links between exposure and damage in developing wildlife and humans. Based on this new knowledge, opportunities abound for extensive multi-disciplinary research involving developmental neurotoxicity.

Five spontaneous deaths associated with Clostridium difficile in a colony of cotton-top tamarins (Saguinus oedipus).

Clostridium difficile toxin was detected in the feces of five cotton-top tamarins (Saguinus oedipus) that died spontaneously over a period of 10 weeks. Deaths occurred subsequent to antibiotic therapy for infectious diarrhea associated with Campylobacter spp. Relevant clinical signs of disease prior to death included weight loss, watery diarrhea, hematochezia, weakness, and sudden collapse. On histologic examination of the colon at necropsy, pseudomembranous colitis was evident in two cases, a lesion consistent with C. difficile lesions in humans. This finding prompted submission of feces for C. difficile toxin analysis from these five cases. Four of the tamarins were from a single room, and the fifth was housed nearby. The proximity of the cases raises the possibility of environmental contamination by resistant C. difficile spores or fecal spread of the organism as reported in hospitals, day-care centers, and nurseries. The relative importance of C. difficile and its potential role as an unrecognized cause of enteric disease secondary to antibiotic therapy in nonhuman primates is discussed.

Mammographic changes in postmenopausal women on hormonal replacement therapy.

The purpose of this study was to investigate the extent of the effects of hormonal replacement therapy (HRT) on the mammographic breast pattern in postmenopausal women. In a hospital-based study mammographic examinations of 81 postmenopausal women were evaluated retrospectively, before and after 1-2 years of treatment with oestrogens or a combination of oestrogens and progestagens. Each individual mammographic film was examined separately, and the glandular tissue was classified according to a modified Wolfe classification. In a screening-centre-based study two consecutive mammograms, with a 2-year interval, of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated retrospectively. In the hospital-based study 31 % of patients treated with combination HRT showed an increase in fibroglandular tissue compared with only 8.7 % in the group treated with oestrogens alone. The difference was statistically significant (p = 0.046). In the screening-based study 14.3 % of the women using hormonal therapy showed an increase, whereas in the non-users no increase was found (p = 1.24 x 10(-10)). After beginning HRT many women (between 14 and 25 % in our experience) can be expected to undergo a mammographically detectable increase in fibroglandular tissue. Radiologists should be aware of the aetiology of such changes, and can obtain information on HRT most conveniently by having the technologist routinely question each patient.

A randomised study to compare the efficacy and safety of new 17 beta-oestradiol transdermal matrix patch with Estraderm TTS 50 in hysterectomised postmenopausal women. The Lyrelle Study Group.

This study was designed to compare the efficacy and safety of two sizes of Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50, a reservoir system. Three hundred and ninety-four (394) hysterectomised postmenopausal women between 30 and 65 years of age participated in this open-label, randomised, multicentre clinical trial. The main efficacy criterion was the reduction in the mean number of hot flushes per day at six months. Secondary efficacy end points included other climacteric symptoms as well as various psychofunctional and genitourinary disorders. A significant decrease from baseline in the mean number of hot flushes/day was observed in all three groups from the end of cycle 1, reaching 90% at the end of cycle 7. there was no statistically significant difference between Lyrelle 50 and Estraderm at any time point for any parameter; however, between-group differences between Lyrelle 80 and Estraderm for various parameters were seen in the first three cycles in favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all three groups, without significant between-group differences. We conclude that the new Lyrelle patch is a highly effective system for transdermal oestrogen replacement therapy that may enhance long-term patient compliance.

The effect of sequential three-monthly hormone replacement therapy on several cardiovascular risk estimators in postmenopausal women.

OBJECTIVE: To investigate the changes in plasma lipids and lipoproteins, low-density lipoprotein (LDL) oxidizability, and plasma homocysteine during postmenopausal sequential 3-monthly hormone replacement therapy. DESIGN: Open longitudinal prospective study. SETTING: Gynecological outpatient department of a university hospital. PATIENT(S): Thirty-nine healthy nonhysterectomized postmenopausal women. INTERVENTION(S): Oral conjugated estrogen, 0.625 mg/d, combined with oral medrogestone 10 mg/d during the last 14 days of each 84-day treatment cycle. The treatment was given for four treatment cycles of 84 days (1 year). MAIN OUTCOME MEASURE(S): Plasma lipids and lipoproteins, LDL oxidizability, and plasma homocysteine. RESULT(S): After 1 year of treatment plasma concentrations of total cholesterol and LDL cholesterol were 3.5% and 8.7% lower, respectively. High density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides were 6.5%, 9.0% and 16% higher, respectively. Apolipoprotein B concentration remained unchanged. The results on LDL oxidizability were inconsistent. Plasma homocysteine decreased with 12.3% during the first 6 months of treatment in women with higher homocysteine concentrations at baseline. These values returned to baseline levels during the second half year of treatment. CONCLUSION(S): This sequential hormone regimen induced beneficial changes in the conventional lipid and lipoprotein risk estimators, whereas the observed changes in the other markers remained inconclusive and/or of minor importance.

The effects of a low-dose gestodene-containing oral contraceptive on endometrial histology in healthy women.

OBJECTIVE: In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 micrograms gestodene and 20 micrograms ethinylestradiol were assessed. METHOD: Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15-21 in cycle 6 for 13 subjects (Group A) and during days 15-21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B). RESULTS: All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Pre-decidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6. CONCLUSIONS: With monophasic gestodene/ethinylestradiol 75 micrograms/20 micrograms, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Changes in androgens during treatment with four low-dose contraceptives.

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

PIP: Health researchers randomly assigned 100 healthy women aged 18-38 from the Netherlands and Saudi Arabia to one of four various oral contraceptive (OC) groups to undergo six cycles of OC therapy so they could evaluate changes in plasma concentrations of sex hormone binding globulin (SHBG), corticosteroid-binding globulin (CBG), albumin (Alb), testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A), dehydro-epiandrosterone-sulphate (DHEA-S), and 17 alpha-hydroxyprogesterone (17OHP). The four monophasic OCs were Cilest (35 mcg ethinyl estradiol [E2] and 250 mcg norgestimate), Femodeen (30 mcg E2 and 75 mcg gestodene), Marvelon (30 mcg E2 and 150 mcg desogestrel), and Mercilon (20 mcg E2 and 150 mcg desogestrel). There were 12 dropouts. Neither body weight nor blood pressure changed significantly during the study. All steroidal serum parameters (T, FT, DHT, A, DHEA-S, 17OHP, Alb) fell significantly during the six cycles of OC treatment (ratio of decrease, 1.3-3), regardless of OC type. These changes had appeared after cycle 4. The only significant difference between the OC groups was that the mean decrease of DHEA-S for Mercilon was lower than that for the other OC groups (21% vs. 43% for Cilest, 44% for Marvelon, and 34% for Femodeen; p 0.05). SHBG and CBG rose greatly during OC use in all four OC groups (mean increase = 263% and 94%, respectively; p 0.05). The increase in CBG was significantly less in the Mercilon group than in the other OC groups (74% vs. 96% for Cilest, 101% for Femodeen, and 102% for Marvelon; p 0.05). These findings show that OC use changed the endogenous androgen environment in the direction of hypoandrogenism. Thus, all four OCs can equally treat androgen-related syndromes (e.g., acne and hirsutism).

Gonadotropin hyperstimulation influences the 35S-methionine metabolism of mouse preimplantation embryos.

The effects of gonadotropin stimulation on mouse embryo uptake and incorporation of 35S-methionine were studied. We found that the uptake of 35S-methionine was reduced in embryos of stimulated females in both the two-cell and the blastocyst developmental stage. The incorporation of 35S-methionine into protein was not statistically significantly different between the embryos of stimulated and those of unstimulated females. Qualitatively, protein synthesis was equal in both groups as determined with one-dimensional SDS-PAGE. The results are discussed and we conclude that mouse embryo viability in vivo is decreased by ovarian stimulation.

Influence of occupational physical activity on pregnancy duration and birthweight.

OBJECTIVES: The influence of occupational physical activity on pregnancy duration and birthweight was examined. METHODS: In this prospective study information on levels of occupational physical activity was collected during a personal interview before pregnancy, and possible changes were registered during follow-up, which lasted until after birth. Data on pregnancy duration and birthweight were obtained from midwives, physicians, and obstetricians. The occupational energy expenditure was operationalized in intensity and fatigue scores, which were studied as such and in combination with workhours and work speed. The occupational biomechanical load was operationalized in a peak and a chronic pressure score. RESULTS: The participants were part of a group of 260 cleaners, kitchen staff, and clerical workers enrolled from 39 Dutch hospitals between August 1987 and January 1989 before they became pregnant. One hundred and twenty-eight of these women were eligible for study because they became pregnant, they worked at least six weeks during pregnancy, and information on work aspects during pregnancy and pregnancy outcome was complete. Work with a high intensity score, and to a less extent work with a high fatigue score, had the most outstanding effect (up to 18 d shorter) on pregnancy duration when the work speed was high. None of the studied aspects of occupational physical activity showed a relevant influence on birthweight when adjusted for pregnancy duration. CONCLUSIONS: This study indicates that the levels of occupational physical load found in the work of nonmedical hospital staff, especially when combined with high work speed, can lead to a shorter pregnancy period.

Semen quality and frequency of smoking and alcohol consumption--an explorative study.

OBJECTIVE: To study the contribution of smoking and alcohol consumption to semen quality. DESIGN: Retrospective analysis. SETTING: University-based fertility clinic. PATIENTS AND METHODS: Smoking and alcohol consumption were investigated in a control group (68) and in a group of 47 subjects with defined poor semen quality (PSQ). The control group was composed of subjects whose semen showed a greater than 60% morphological normality, a greater than 60% motility with a linear progression, and a density of greater than 20 million spermatozoa/mL. The group with PSQ was composed of subjects whose semen showed a less than 30% morphological normality, less than 60% motility, characterized by slow, weak motility, and a density of less than 20 million spermatozoa/mL. Medical dossiers were studied regarding the life style of the subjects. RESULTS: The distribution of heavy smokers and light smokers did not differ statistically between the groups. There appeared to be a higher, but statistically insignificant, proportion of heavy smokers in the PSQ group (50%) compared to the control group (32.3%; P < .1); nor were significant differences found between cases and controls with respect to alcohol consumption pattern. In the PSQ group, a comparison of the semen characteristics of the daily drinkers with those of all the other subfertile patients showed no statistical difference concerning semen volume (4.1 +/- 1.9 vs. 3.3 +/- 1.3 mL; P > .1), sperm density (10.6 +/- 7.8 vs. 8.9 +/- 5.8 million spermatozoa/mL; P > or = .1), and percentage of motile spermatozoa (27.0 +/- 15.1 vs. 25.5 +/- 16.1%; P > .1). However, a lower percentage of normal sperm morphology was observed in the daily-drinker group (17.6 +/- 7.2% vs. 23.0 +/- 6.5% for the other subfertile patients; P < .05). CONCLUSION: Factors such as smoking and alcohol consumption do not seem to play a pivotal role in the etiology of poor semen quality, but a pattern of excessive alcohol consumption may decrease further an already low percentage of sperm with normal morphology.

Comparative evaluation of the androgenicity of four low-dose, fixed-combination oral contraceptives.

Changes in endogenous androgen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives (OCs). One hundred women were randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4) 30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded, and plasma levels of the following variables were recorded: sex-hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and hydroxyprogesterone. The free androgen index was also calculated. These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles. There were no statistically significant differences in androgenic variables among the four OCs. The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations (20% vs. 45%). Concentrations of SHBG and CBG increased significantly in all four groups (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations (about 100%). The four modern, low-dose OCs tested had similar impacts on endogenous androgen metabolism, yielding significant decreases in testosterone, dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be beneficial in women with androgen-related syndromes such as acne and hirsutism. Large studies are under way to establish which of the third-generation OCs is the least androgenic. In vitro studies suggest that norgestimate has the least androgenic profile.