Britt-Marie Landgren

Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age

Normal probability plots were used to analyse the distribution of follicular phase length in a population of 293 apparently ovulatory menstrual cycles from women aged between 18 and 39 years. The length of the follicular phase was defined as the interval (in days) from the onset of menstruation up to, but not including, the day of the LH peak. Follicular phase length appeared to be log‐normally distributed and graphical inspection of the probability plot suggested that the geometric mean (and 95% confidence limits) of follicular phase length in this study group was 12–9 (10–3 to 16–3) days. There was a significant decrease (P<0.001) in follicular phase length with chronological age, from 14–2 days in women aged 18–24 years to 10.4 days in women aged 40–44 years.

The influence of stress and state anxiety on the outcome of IVF-treatment: Psychological and endocrinological assessment of Swedish women entering IVF-treatment

Background. Comparing stress levels in women entering IVF treatment with those of fertile controls as well as relating these levels to the outcome of IVF.

Reproductive health, use of estrogen and experience of symptoms in perimenopausal women : a population-based study

OBJECTIVE The aim of the study was to examine reproductive health, use of estrogen, lifestyle, experience of menopausal symptoms and work-role related issues in a population-based sample of perimenopausal women. METHODS All women aged 48 years and residing in the catchment area of the Karolinska Hospital were recruited through the Swedish population register. They received a questionnaire covering sociodemographic background, reproductive health and gynaecological characteristics, social and work role related issues as well as a symptom rating scale. RESULTS Seventy percent of the women returned the questionnaire. Of these, 73% were premenopausal, 21% were postmenopausal and 6% were perimenopausal. Hormone replacement therapy was used by 7.5% of the respondents and the rate of hysterectomy was 8.6%. Regular exercise was reported by 44.4%. Factor analysis of the symptom ratings yielded four independent dimensions: Negative Moods, Vasomotor symptoms, Decreased Sexual Desire and Well-being. Multiple regression analyses showed that only vasomotor symptoms were significantly related to menopausal status. Negative Mood and Reduced Sexual Interest were better explained by the presence of vasomotor symptoms and by reproductive health and lifestyle variables such as current or previous PMS, dysmenorrhea, smoking and lack of exercise. CONCLUSIONS Only vasomotor symptoms were significantly related to menopausal status. Psychosocial and lifestyle variables as well as past or current reproductive health are more important determinants of womens psychological well-being during transition to menopause than menopausal status.

Coexpression of pinopodes and leukemia inhibitory factor, as well as its receptor, in human endometrium

OBJECTIVE To determine cell-type-specific expression of leukemia inhibitory factor (LIF) and LIF receptor (LIFR) proteins relative to formation of pinopodes in human endometrial samples. DESIGN Prospective clinical study. SETTING Hospital-based unit for reproductive health and university-affiliated reproductive research laboratories. PATIENT(S) Twenty-six healthy fertile women with normal menstrual cycles. MAIN OUTCOME MEASURE(S) Routine blood and urine samples were obtained, and vaginal ultrasonography and endometrial biopsy were performed. Pinopode formation and expression of LIF and LIFR were examined in endometrial samples. RESULT(S) Samples obtained during LH days 6 through 9 had pinopodes at different developmental stages. Both surface and glandular epithelial cells expressed maximal levels of LIF and LIFR protein, in biopsy samples showed fully developed pinopodes. Immunostaining of LIF was more intense in the glandular epithelium, whereas immunostaining of LIFR was most intense in the surface epithelium. Before and after the appearance of pinopodes, LIF and LIFR immunostaining was less intense or faint. Stromal endometrial cells showed faint LIF accumulation. CONCLUSION(S) The simultaneous positive spatial and temporal expression of pinopodes and LIF and LIFR proteins in endometrial samples from healthy women suggests that both molecular and structural cell changes are important in the initiation of human blastocyst implantation.

STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE

In an attempt to analyze the multiple changes and interactions in circulating steroid levels in the peri-ovulatory and peri-menstrual periods, the plasma levels of immunoreactive luteinizing hormone (LH), progesterone and unconjugated pregnenolone, dehydroepiandrosterone, testosterone, oestradiol and oestrone were assayed daily during a complete cycle in 17 normally menstruating women. In 14 of the 17 subjects studied androstenedione and unconjugated dihydrotestosterone were also estimated. The day of the LH-peak and the first day of menstruation, respectively, were used to synchronize the peri-ovulatory and peri-menstrual plasma levels of the various steroids. With the exception of dehydroepiandrosterone and dihydrotestosterone, the plasma levels of all steroids exhibited significant, but different changes during the cycle. Testosterone levels showed a slight but significant increase around the LH-peak, whereas the levels of pregnenolone and androstenedione were higher in the post-ovulatory than in the pre-ovulation periods. The levels of oestradiol and oestrone, as well as the ratios of oestradiol to oestrone gradually increased from the low values observed in the early proliferative phase to pre-ovulatory peak values. The relationship between peaks of oestradiol and oestrone and that of LH exhibited great individual variation. The same was true for the individual oestradiol to oestrone ratios. The combination of several steroidal signals did not improve the predictive value of the analyses. However, an increase of individual progesterone values by at least 0.35 ng/ml from the day preceding the LH-peak to the day of the LH-peak was observed in 13 of the 17 subjects. It is suggested that for the early detection of the LH surge and prediction of the subsequent ovulation daily assays of plasma progesterone are of more value than the assay of the other steroids investigated.

Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors

OBJECTIVE To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B. DESIGN Prospective clinical study. SETTING Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories. PATIENT(S) Twenty-seven healthy fertile women with normal menstrual cycles. INTERVENTION(S) Urine and blood sampling for hormone measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME MEASURE(S) Appearance of the endometrium on light microscopy, pinopode formation, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and expression of progesterone receptors A and B and estrogen receptors alpha and beta. RESULT(S) Pinopode formation and regression were closely associated with increases and decreases, respectively, in serum progesterone concentration. At pinopode development, levels progesterone receptors A and B in the glandular and luminal epithelial cells decreased; this effect was mainly dependent on the absence of progesterone receptor B. Serum estrogen levels and levels of estrogen receptor alpha and beta did not correlate with pinopode formation. CONCLUSION(S) The increase in serum progesterone level and down-regulation of progesterone receptor B are important in development of pinopodes.

Hormonal effects of the 300 μg norethisterone (NET) minipill

Abstract The ovarian effects of the 300 μg norethisterone (NET) minipill were investigated in 43 normally menstruating women by the daily analysis of the peripheral plasma levels of estradiol and progester-one in a pretreatment (control) cycle and during the second month of NET administration. During the latter period, the daily levels of NET were also measured. The assessment of normal values characterizing an ovulatory cycle was based on the results of a previous study, indicating i.e. that in a normal luteal phase, 95 out of 100 normally menstruating women of the local study population exhibit plasma progesterone levels exceeding 16 nmol/1 for a minimum of five days. The present study revealed four characteristic and distinctly different types of ovarian reaction to the NET minipill; seven subjects (16%) exhibited no signs of follicular or luteal activity as evidenced by the low estradiol and progesterone levels ( group A ), ten subjects (23%) showed a marked cyclic follicular activity, but no luteal function (group B), nine subjects (21%) had a normal follicular activity, but a significantly reduced (insufficient) luteal activity ( group C ),and 17 subjects (40%) exhibited estradiol and progesterone profiles which were indistinguishable from those found in normally menstruating women, in general, and in their pretreatment cycles, in particular ( group D ). Compared to the characteristics of the pretreatment cycles, the administration of NET resulted in a shortening of the luteal phase in group C and in a lengthening of the follicular phase together with a shortening of the luteal phase in group D. The plasma levels of NET closely reflected the regularity (or irregularity) of pill taking by the various subjects and the time interval elapsing between pill taking and blood withdrawal. There was no correlation between the levels of NET and the types of ovarian reaction induced, or of the bleeding profile. Compared to the bleeding profile of the pretreatment period, the administration of NET increased the number of episodes and the number of days with bleeding and spotting and reduced the average bleeding-free interval. In this limited study, no difference could be established in the bleeding patterns observed in the various groups. An important aspect of this investigation was to assess whether or not the ovarian reaction to the NET minipill can be predicted from the analysis of previous reproductive events and/or the hormonal profile of the pretreatment cycle. There was a significant excess of nulliparous women in group A. Compared to the women of the three other groups, they exhibited, in their pretreatment cycle, a diminished progesterone maximum together with a prolonged follicular phase and shortened luteal phase. On the other hand, the 17 women of group D showed a shorter follicular phase and longer luteal phase than the 26 women in groups A+B+C. It is concluded that the relative length of follicular and luteal phases has a predictive value for the expected ovarian reaction to the NET minipill. Hence, the efficacy of the minipill might be increased by judicious selection of women exhibiting, during the pretreatment period, a high follicular to luteal phase ( F L ) ratio (measured, for instance, by basal body temperature, or some other simple method).

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Effect of conjugated estrogen on peripheral flow-mediated vasodilation in postmenopausal women

Estrogen replacement protects against cardiovascular morbidity and mortality in postmenopausal women. Conjugated estrogen is the main hormone used in these studies. However, the vascular effects of this type of estrogen are, to a large extent, unexplored. The objective of this study was to evaluate short-term endothelium-dependent vascular effects of intravenously conjugated estrogen at 2 dose levels. Eleven postmenopausal women were included. Each study subject was given 2.5 and 5 mg of conjugated estrogen or placebo in random order with at least 1 week between each investigation in a double-blind study design. The vascular reactivity of the brachial artery was studied using the duplex technique before and 30 minutes after the intravenous administration of study drug. Reactive hyperemia was used to study the flow-mediated vasodilation. Serum estradiol increased significantly and dose dependently 5 minutes after conjugated estrogen infusion. The flow-mediated vasodilation at baseline before drug administration was 1.8 +/- 2.0% (mean +/- SD) after an average 400% increase in local blood flow. Conjugated estrogen at a dose of 2.5 mg caused an increase in flow-mediated vasodilation from 1.8 +/- 2.1% at baseline to 5.4 +/- 2.8% after infusion (p <0.05 vs placebo), whereas 5 mg caused an increase from 1.9 +/- 1.5% at baseline to 7.0 +/- 3.3% after infusion (p <0.05 vs placebo). Intravenous injection of conjugated estrogen significantly improves the peripheral vascular reactivity in postmenopausal women.

Effects of various iuds on the composition of cervical mucus

The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage.