Changes in breast volume during normal menstrual cycle and after oral contraceptives.

The volume of the left and right breasts was measured daily in four nulliparous women during normal menstrual cycles and after the use of oral contraceptives. Breast volume increased significantly in the second half of both normal and contraceptive-controlled cycles. The mean total change in volume throughout the cycle was 100 ml under natural conditions and 66 ml on oral contraceptives.     

Cortisol and memory retrieval in women: influence of menstrual cycle and oral contraceptives

Rationale Studies in rodents observed that the effects of stress on memory are modulated by gonadal hormones. In animals and humans, stress and cortisol treatment impairs memory retrieval.Objectives To investigate if the acute impairing effect of cortisol on memory retrieval in women is influenced by endogenous or exogenous gonadal steroids.Methods Three groups of women were studied: women during mensis (n=13), women in the luteal phase (n=14), and women using oral contraceptives (OCs; n=20). In a double-blind crossover fashion, they received cortisol (30 mg) or placebo 1 h prior to memory retrieval testing.Results Overall cortisol led to a significant impairment of memory retrieval. Further exploratory analysis using t tests showed that both groups of naturally cycling women were significantly impaired (p<0.05), while no effect was apparent in the OC users (p=0.29).Conclusions The current results could suggest that OC use is associated with a reduced sensitivity of the brain to acute cortisol elevations. In contrast, menstrual-cycle-associated changes in estradiol and progesterone concentrations appear to have no strong influence on this acute cortisol effect. The underlying neurobiological mechanisms of these behavioral findings remain to be elucidated.     

Effects of acute ethanol administration on rat plasma amino acids and related compounds

Using high performance liquid chromatography (HPLC) with fluorometric detection, thirty-three amino acids (AA) and related compounds were measured in plasma obtained from catheterized rats over a 3-hr period following a 2 g/kg, i.p., injection of ethanol. The concentrations of twenty-three of these compounds had decreased significantly 15 min after the injection, and twenty-three remained depressed for the 3-hr period. Marked reductions were noted for alanine and arginine. Glutamic acid, 1-methylhistidine and 3-methylhistidine were unaffected by ethanol. During these studies individual differences were observed in that some rats showed marked biochemical changes, whereas other rats showed only minimal responses. These observations indicate that ethanol administration may have a significant and long-lasting impact on plasma amino acid biochemistry.     

Disposition of serum steroids in response to combined oral contraceptives and menstrual cycle phases: A double-blind,randomized, placebo-controlled study

To analyze doping control samples from female athletes demands understanding of non-doping factors that affect the steroid profile. These could be physiological factors such as exercise, alcohol consumption, hormonal changes during the menstrual cycle, or the effect of commonly used approved drugs like combined oral contraceptives. Urine samples have been the main way of doping testing, but serum samples are proposed as a complement. Testosterone, dihydrotestosterone, or the ratio of testosterone and androstenedione has been proposed as a biomarker for testosterone doping because it increases after transdermal testosterone administration. In this double-blind, randomized, placebo-controlled study of 340 healthy females, we analyzed the serum steroid levels, including glucuronide metabolites, before and after 3 months of combined oral contraceptives or placebo. At follow up, sample collection in the placebo group was randomly distributed between different menstrual cycle phases. This enabled to analyze changes in concentrations between the follicular, ovulation, and luteal phases. Combined oral contraceptives decreased all serum steroids including the glucuronide metabolites. As expected, serum testosterone levels increased during the ovulation phase, and also androstenedione and androstenediol, whereas the glucuronide metabolites remained unaffected. Neither combined oral contraceptives nor menstrual cycle phases did affect the ratio of testosterone and androstenedione in serum, and consequently this ratio seems promising as a marker of doping with endogenous anabolic androgenic steroids in women.     

Effects of manufacturing oral contraceptives on blood clotting.

In monitoring the effects of industrial exposure resulting from the pharmaceutical manufacture of oestrogen-progestogen combinations by coagulation studies acceleration of some clotting tests was found. The most pronounced changes were in workers most closely associated with the industrial process. Less pronounced changes were found in women employees not closely concerned with the processing and may have been secondary to the postmenopausal bleeding to which they were prone. A safer work procedure elaborated by the Employment Medical Advisory Service was monitored by clotting studies for over a year but the three most highly exposed subjects showed no substantial improvement.     

Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers.

The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle. Female volunteers (n = 16) with a regular menstrual cycle (28 +/- 4 days) received a single oral dose of 80 mg eletriptan during each of the four cycle phases: phase 1 (menses), days 1 to 4; phase 2 (follicular), days 6 to 10; phase 3 (ovulatory), days 11 to 13; and phase 4 (luteal), days 21 to 24. Eletriptan plasma concentrations were determined from serial plasma samples taken during a 24-hourperiod after dosing. Blood pressure, pulse rate, and ECG measurements were performed at baseline, 1 and 24 hours after dosing. No significant differences between phases were observed for maximum plasma concentration (cmax, range of means = 188-234 ng/ml), time to maximum concentration (tmax, range of means = 1.8-2.5 h), or systemic exposure (area under the curve [AUC], range of means = 1194-1514 ng x h/ml). Although there was a statistically significant difference in the terminal phase elimination rate constant (kel) between phases 1 and2 (0.175/h vs. 0.158/h, p = 0.044), the corresponding difference in terminal phase half-life (t 1/2) (4.0 h vs. 4.4 h) was not considered to be clinicallyrelevant. No clinically relevant differences in blood pressure, pulse rate, or ECG were observed, and the incidence, nature, and severity of adverse events were similar in all phases. The different phases of the menstrual cycle had no clinically significant effect on the pharmacokinetics, safety, or tolerability of oral 80 mg eletriptan in healthy females.     

Effects of subjects' sex, and intake of tobacco, alcohol and oral contraceptives on plasma phenytoin levels.

1. Steady state plasma phenytoin levels in 210 epileptic patients were studied by computerized analysis of covariance to determine whether the subject's sex, alcohol intake, tobacco smoking or use of oral contraceptives influenced the relation between plasma drug level and drug dose. 2. Sex, tobacco smoking and alcohol usage had no statistically significant effect. There was a trend towards higher phenytoin levels relative to drug dose in oral contraceptive users. 3. This finding prompted an additional study of plasma phenytoin levels in 40 oral contraceptive users and 135 aged matched non-users. Analysis of covariance again showed higher plasma phenytoin levels relative to drug dose in users of oral contraceptives (P = 0.061). 4. This finding raised the possibility that the relation between plasma phenytoin level and drug dose differed between males and females who did not use oral contraceptives. However, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use oral contraceptives and 101 males (both groups aged 15 to 70 years) no statistically significant difference was found.     

Urinary steroid profile in females – the impact of menstrual cycle and emergency contraceptives

Today's doping tests involving longitudinal monitoring of steroid profiles are difficult in women. Women have more complex hormonal fluctuations than men and commonly take drugs such as hormonal contraceptives that are shown to affect biomarkers used in these doping tests. In this study, we followed six women's urinary steroid profile during one menstrual cycle, including both glucuronides and sulfate conjugated fractions. Additionally, we studied what happens to the steroidal module of the Athlete Biological Passport (ABP) after administration of an emergency contraceptive (levonorgestrel, NorLevo®). The study shows that there are large individual variations in all metabolites included in the ABP and that the administration of emergency contraceptives may lead to suspicious steroid profile findings in the ABP. Urinary epitestosterone concentration increased during the menstrual cycle, leading to a decrease in the testosterone/epitestosterone ratio. The ratios followed in the ABP varied widely throughout the menstrual cycle, the coefficient of variation (CV) ranging from 4 to 99%. There was a 3‐fold decrease in epitestosterone 24 h post administration of the emergency contraceptive pill and androsterone, etiocholanolone, and 5β‐ androstan‐3α,17β‐diol concentrations decreased about 2‐fold. When analyzed with the ABP software, one of the six women had an atypical profile after taking the emergency contraceptive. Furthermore, we could not find any alterations in excretion routes (i.e., if the metabolites are excreted as glucuronide or sulfate conjugates) during the menstrual cycle or after administration of emergency contraceptive, indicating no direct effect on phase II enzymes. Copyright © 2016 John Wiley & Sons, Ltd.     

Value of ultrasound during the menstrual cycle and early pregnancy

Ultrasound is a recently introduced technique that allows repeated noninvasive imaging of the uterus, ovaries and associated structures. It offers a relatively simple method for the repeated examination of the abdominal organs including growing fetuses, and is increasingly being used to measure blood flow in the identification of disease states. The clinical applications of real time pelvic ultrasonography are principally in the field of gynaecology to assess anatomical normality, and to monitor the progress of natural and stimulated cycles in assisted reproductive techniques. Once infertility treatment has been successful, ultrasound has proved to have a great value, when combined with established endocrinological parameters, to monitor the development of pregnancy, and the normality of fetal growth.     

Variation of sex chromatin percentage during menstrual cycle and menopause

Buccal smears were obtained from 2 groups of women to study the percentage of Barr bodies. The first group comprised of normal women with regular menstrual cycle between the age group 18-22 years. The second group comprised of Menopausal women in the age group 47-55 years. A definite variation in percentage of barr bodies was observed in the first group whereas the percentage remained normal in the second group.