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Biomedical subjects

R Rolland

Publications and source records attributed to R Rolland.

At least 19 recordsLinked to original sources

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.

Adolescent↗

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.

Aged↗

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.

Cardiovascular Diseases↗

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.

17-alpha-Hydroxyprogesterone↗

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.

Animals↗

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.

Adult↗

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.

Animals↗

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.

Adult↗

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.

Adult↗

Cigarette smoking, alcohol consumption, and caffeine intake and fecundability.

BACKGROUND: In a prospective study the effect of the behavioral risk factors of both partners on fecundability was studied. METHODS: Information was collected on smoking habits, alcohol consumption, and caffeine intake (e.g. coffee, tea, and cola consumption) by interviewing 259 female nonmedical hospital workers, i.e., clerical staff, cleaners, kitchen and restaurant workers, and their partners, who were planning a pregnancy. The occurrence of pregnancy was tested prospectively during the 12 months after enrollment. RESULTS: Among the participants as well as among their partners, smoking a moderate number of cigarettes (1-10/day) was associated with higher fecundability (i.e., the probability of becoming pregnant each month) than among those not smoking (participant: OR = 1.4 (95% CI, 0.9-2.2); partner: OR = 2.1 (95% CI, 1.2-3.5)). The level of alcohol consumption in the female partner was not related to fecundability. However, in the male partner, there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 (OR = 1.6; 95% CI, 1.0-2.4). Participants with a moderate caffeine intake (400-700 mg/day) showed a higher fecundability than those with a lower intake level (ORadjusted = 2.1 (95% CI, 1.2-3.7)). Heavy caffeine intake (> 700 mg/day) among partners was negatively related to fecundability when compared with the lowest intake level (ORadjusted = 0.6 (95% CI, 0.3-0.97)). CONCLUSIONS: This study does not support the hypothesis that moderate cigarette smoking, caffeine intake, and alcohol consumption have an adverse influence on fecundability.

Adolescent↗

Hormone replacement therapy increases serum 1,25-dihydroxyvitamin D: A 2-year prospective study.

Osteoporosis is a common disorder in postmenopausal women, which is probably due to decreased ovarian function. Currently, hormone replacement therapy (HRT), involving administration of estrogen and progestogen, is successfully applied to reduce bone resorption. We studied the effect of HRT on 23 postmenopausal women. This consisted of a combination of 17 beta-estradiol and dydrogesterone, on the serum level of 1,25-dihydroxyvitamin D (1,25(OH)2D) after 0, 6, 12, and 24 months. We found mean serum concentrations (+/- SD) of 1,25(OH)2D of 130.5 pmol/liter (46.1), 152.7 pmol/liter (45.1), 170.8 pmol/liter (64.0), and 155.2 pmol/liter (59.7), respectively. The baseline values in these women were found to be significantly lower than those during therapy (P < or = 0.005). No statistically significant differences were observed when comparing the estrogen-only phase with the combined estrogen-progestogen phase. It is concluded that HRT results in an increase in the serum 1,25(OH)2D concentration which lasts for at least 2 years. This increase may partly explain the preventive effect of HRT on osteoporosis. Furthermore, these results suggest that dydrogesterone does not influence the estrogen-induced changes in serum 1,25(OH)2D concentration.

Administration, Oral↗

Changes in the low-density lipoprotein profile during 17 beta-estradiol-dydrogesterone therapy in postmenopausal women.

Changes in the low-density lipoprotein (LDL) subfractions, determined with gradient gel electrophoresis (GGE), were prospectively studied during hormone replacement therapy (HRT) in 23 healthy nonhysterectomized postmenopausal women. LDL subfractions were analyzed by densitometric scanning of the gels. We observed significant changes in the LDL subfraction profile toward a smaller particle size (P < .001). These changes could almost completely be attributed to the hormonal treatment regimen (P < .01), and may indicate an effect partially opposite to the other reported changes in the lipid profile.

Dydrogesterone↗

Changes in the withdrawal bleeding pattern and endometrial histology during 17 beta-estradiol-dydrogesterone therapy in postmenopausal women: a 2 year prospective study.

OBJECTIVE: To describe changes in the withdrawal bleeding pattern and endometrial histology during a sequential 17 beta-estradiol-dydrogesterone regimen in postmenopausal women. DESIGN: Open-label, non-comparative, prospective study. SETTING: Gynecological outpatient department of a university hospital. PATIENTS: Twenty-seven healthy non-hysterectomized postmenopausal women. INTERVENTIONS: Continuous micronized 17 beta-estradiol supplementation, 2 mg daily, and cyclic administration of dydrogesterone, 10 mg daily for the first half of each 28 day treatment cycle. MAIN OUTCOME MEASURES: Changes in the characteristics of the withdrawal bleeding pattern and the endometrial biopsy histology during 2 years of treatment. RESULTS: The initial withdrawal bleeding was comparable to normal menstruation with respect to amount and duration. During the 2 years of treatment the bleeding showed a significant tendency to become shorter with less blood loss. This was mainly the result of the decrease (P < 0.001) in the number of days per cycle with bleeding grade II (normal menstruation). None of the women developed endometrial hyperplasia, and in almost all women the given hormone replacement therapy regimen induced secretory or atrophic changes of the endometrium. CONCLUSIONS: This sequential 17 beta-estradiol-dydrogesterone regimen can be regarded as safe with respect to the prevention of endometrial disease and appeared to foster patient compliance.

Biopsy↗

Effect of conjugated estrogens with and without medrogestone: a prospective study.

OBJECTIVE: To study the possible changes in serum lipids and lipoproteins during hormone replacement therapy with special emphasis on the possible effects brought about by the progestogen. DESIGN: Open-label randomized prospective comparative study. SETTING: Gynecological outpatient department of an university hospital. PATIENTS: Thirty-three healthy hysterectomized postmenopausal women. INTERVENTIONS: Continuous oral supplementation with conjugated estrogens, 0.625 mg daily, was administered either alone (group I; N = 18) or in combination with cyclic medrogestone, 5 mg daily during the last 12 days of each 28 days treatment cycle (group II; N = 15). MAIN OUTCOME MEASURE: Changes in serum lipids, lipoproteins and apolipoproteins after three, six and 13 treatment cycles. RESULTS: After 1 year of treatment significant increases were observed in mean high-density lipoprotein (HDL) cholesterol, its subfractions, and apolipoprotein A-I in group I and II: HDL cholesterol: +25.2% and +12.1%, respectively; HDL2 cholesterol: +47.4% and +23.5%, respectively; HDL3 cholesterol: +18.1% and +11.2%, respectively; apolipoprotein A-I: +23.0 and +14.8%, respectively. Comparing the two study groups no significant differences were found in lipid changes during the study period, except for HDL2 cholesterol. CONCLUSION: Supplementation with conjugated estrogens, with and without medrogestone, and given for a longer period, demonstrated a beneficial influence on serum lipoproteins with almost no differences between the two treatment regimens.

Administration, Oral↗

Circulating inhibin levels in lactating and nonlactating women.

OBJECTIVE: To investigate the role of inhibin in the human puerperium, by measuring serum levels of immunoreactive inhibin in both lactating and nonlactating women. DESIGN: Prospective, comparative, open study. SETTING: Department of obstetrics and gynecology of a university hospital. PATIENTS: Fourteen healthy women who delivered at term: seven lactating women and seven nonlactating women treated with the dopamine-agonist CV 205-502. MAIN OUTCOME MEASURES: Serum immunoreactive inhibin, PRL, FSH, LH, E2, and P. RESULTS: All women showed a rapid decline of immunoreactive inhibin levels during the first postpartum days. Thereafter the pattern depended on the way of feeding. Nonlactating women, with their rapid return of pituitary and ovarian function, showed increasing immunoreactive inhibin levels to a maximum on day 24 (950 +/- 180 U/L). Lactating women did not show ovarian activity despite high FSH levels, and immunoreactive inhibin stayed on a low level (230 +/- 40 U/L on day 24). There was a significant correlation between immunoreactive inhibin and E2. CONCLUSIONS: The rapid decline of immunoreactive inhibin (elimination of placental hormone) is followed by an increase in nonlactating women (production by the maturing follicle) and by persistently low levels in lactating women. The lack of adequate levels of immunoreactive inhibin in lactating women may be an explanation of the relatively high FSH levels during lactation.

Aminoquinolines↗

The influence of occupational physical activity on the menstrual cycle and fecundability.

We examined the influence of the level of occupational physical activity per working hour (intensity score) and per working day (fatigue score) on menstrual function and fecundability in a population of 260 nonmedical female workers who were employed at 39 Dutch hospitals and were planning a pregnancy. We studied the influence of the intensity and fatigue scores as such and in combination with unfavorable working hours (before 8:00 am or after 6:00 pm) and high working speed (working at high speed for more than 50% of the time). The data did not reveal a clear relation between the occupational physical activity levels (representing an estimated energy requirement of up to 3 times the basal metabolic rate) and menstrual function, but the presence of a small effect could have been missed. The fecundability of women with a high fatigue score, particularly in association with unfavorable working hours, was lower than that of women with a low fatigue score (fecundability odds ratio = 0.37; 95% confidence interval = 0.18-0.77). Moderate levels of physical activity, as found in cleaners, kitchen staff, and clerical workers at hospitals, appear to affect the female reproductive system. Fecundability, as measured by the time to pregnancy, seems to be a more sensitive parameter for these biological changes than menstrual function.

Adolescent↗

Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women.

In a prospective study we investigated the possible changes in fasting serum total homocysteine concentrations during continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily during the first 14 days of each 28 day cycle, in 21 healthy non-hysterectomized postmenopausal women. During the first six cycles mean serum homocysteine decreased by 10.9% (P = 0.013), after which no further significant changes were found during the 2 years of treatment. A 16.9% decrease (P = 0.017; n = 8) was found in women with high homocysteine concentrations, while in women with low homocysteine concentrations (n = 13) no significant changes were observed. The observed decrease in high homocysteine concentrations in postmenopausal women may in part contribute to the decreased risk of developing cardiovascular disease during hormone replacement therapy.

Drug Administration Schedule↗