Menstrual cycle length, serum lipids and lipoproteins in a cohort of Italian Mediterranean women: findings from Progetto ATENA

Background and aimsClinical studies suggest that menstrual irregularities are associated with metabolic and hormonal abnormalities, insulin resistance and a hyperestrogenic/hyperandrogenic imbalance, that may influence the risk of cardiovascular disease.Methods and resultsThe association of these abnormalities with the metabolic syndrome suggests that information on lipid patterns at different menstrual cycle length may be of interest in identifying women at higher cardiovascular risk. The association of lipid patterns with menstrual cycle length was evaluated in a cohort of 5062 women participating in the Progetto ATENA Study. Questions were administered to the participants about their cycle lengths at different periods of time over their reproductive life. The period between 20 and 50 years was investigated: normal cycle length was defined as short (≤26 days), medium (between 27 and 29 days) or long (>30 days). Perimenopausal women were excluded and variables adjusted for age, BMI and menopausal status. In 4434 participants serum triglycerides were found to increase with an increased number of days in the menstrual cycle: 106 mg/dl in the short cycle pattern (21–26 days); 113 mg/dl in the medium cycle pattern (27–29 days); and 116 mg/dl in the long cycle pattern (30–31 days), whereas total and LDL cholesterol were found to be higher and HDL was lower in women with longer cycles, but the difference was not statistically significant. The results were very similar when the same adjusted analysis was restricted to a subgroup of 3823 women with a stable cycle length over the fourth and the fifth decade of life.ConclusionsThese results suggest that cycle length may be a marker of higher cardiovascular risk due to associated metabolic and hormonal patterns.     

Effect of dietary fat on length of the follicular phase of the menstrual cycle in a controlled diet setting.

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.     

Reproductive history and hormonal birth control use are associated with coronary calcium progression in women with type 1 diabetes mellitus

CONTEXT: Coronary artery disease is increased in women with type 1 diabetes (T1D), compared with nondiabetic (Non-DM) women. Women with T1D have more menstrual dysfunction and are less likely to use hormonal birth control (BC) than Non-DM women. OBJECTIVE: The purpose of this study was to determine whether coronary artery calcium (CAC) is associated with menstrual dysfunction and BC use in women with T1D. MATERIALS AND METHODS: This was a prospective cohort study, and participants were followed up for an average of 2.4 yr. PATIENTS: Patients included 612 women (293 T1D, 319 Non-DM) between the ages of 19 and 55 yr who had CAC measured twice by electron beam tomography. RESULTS: Irregular menses and amenorrhea were more common in T1D than Non-DM women (22.1 vs. 14.9%, P < 0.05 and 16.6 vs. 7.0%, P < 0.001). T1D women reported less BC use than Non-DM women (79.8 vs. 89.9%, P < 0.001) and reached menarche at an older age (13.1 +/- 1.8 vs. 12.8 +/- 1.5 yr, P < 0.05). Use of BC was associated with less CAC progression in all women, but this association was stronger in T1D women (P value for interaction = 0.02). Irregular menses were associated with greater CAC progression only among T1D women. CONCLUSIONS: A prior history of BC use is associated with reduced CAC progression among all women, with a stronger association in T1D than in Non-DM women. Women with T1D who report irregular menses have increased CAC progression, compared with those with regular menses.     

Irregular ventricular tachycardia: a possible manifestation of longitudinal dissociation within the reentry pathway.

Sustained monomorphic ventricular tachycardia is usually regular; that is, it is associated with constant R-R intervals. In several cases, however, the cycles of ventricular tachycardia are more or less variable. Fifty-four cases of sustained monomorphic ventricular tachycardia were evaluated in order to assess whether tachycardia was regular. Nine cases were defined as irregular (i.e., the R-R cycles varied by more than 40 msec throughout a 1-minute recording). In five cases tachycardia was "regularly irregular," since the R-R cycles could be divided into two separate groups: the group of long cycles and that of short cycles. In these cases the variability manifested according to a defined and constant pattern: bigeminal pattern (alternation of short and long cycles), trigeminal pattern (two short cycles followed by a long cycle), and so on. The regular variability of tachycardia cycle length suggests one of the following possibilities. (1) There are two alternative circuits (a short circuit and a long circuit) that share the same exit pathway. Whenever the reciprocating impulse runs through the short circuit, the R-R cycle is short; but if a block in the short circuit occurs, the impulse runs through the long circuit, resulting in a long R-R cycle. (2) There is a longitudinal dissociation within the reentry circuit; two separate pathways with different inherent conduction velocities are present. When the impulse runs through the fast pathway, the R-R cycle is short; whereas when a block in the fast pathway occurs, the impulse traverses the slow pathway, resulting in a long R-R cycle.     

Inhibition of folliculogenesis in the monkey following early follicular phase administration of an LRH agonist

This study was undertaken to determine if early follicular phase administration of a synthetic luteinizing hormone releasing hormone (LRH) agonist would produce luteal phase defects in the monkey. [D-His(im-Bzl)6,Pro9]LRH N-ethylamide was administered to groups of rhesus monkeys on days 1-3 of the menstrual cycle. Two responses were observed: a) anovulatory menstrual cycles of less than 14 days duration, and b) ovulatory menstrual cycles characterized by unusually long follicular phases. All 4 monkeys with shortened menstrual cycles had prominent increases in serum gonadotrophin and oestradiol concentrations during treatment with the LRH agonist; early menses in these animals was attributed to uterine bleeding upon oestrogen withdrawal. Serum FSH concentrations declined, serum LH concentrations were unaltered, and only 2 of 8 monkeys had elevations in serum oestradiol during ovulatory menstrual cycles. The mean interval from cessation of treatment with the LRH agonist to the next preovulatory gonadotrophin surge was 21.5 +/- 3.2 days in ovulatory menstrual cycles. Corpus luteum function was normal following treatment with the LRH agonist in ovulatory cycles. The results indicate that both the long and short menstrual cycles observed following early follicular phase administration of the LRH agonist to monkeys can be attributed to a profound inhibition in follicle recruitment. [D-His(im-Bzl)6,Pro9]LRH N-ethylamide did not alter corpus luteum function in the monkeys.     

Polycystic ovarian morphology in normal women does not predict the development of polycystic ovary syndrome

CONTEXT: Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome (PCOS); however, the natural history of PCOM is unknown. OBJECTIVE: We hypothesized that the presence of PCOM predisposes the development of PCOS. DESIGN: The study was a longitudinal follow-up study over 8.2 +/- 5.2 yr (mean +/- sd; range 1.7-17.5 yr). SETTING: The study took place in an outpatient setting. SUBJECTS: Women who took part in a previous study as a normal control and had an ultrasound examination (n = 40) participated. INTERVENTION: Subjects underwent an interval menstrual history, physical exam, blood sampling, and repeat ultrasound in the follicular phase. MAIN OUTCOME MEASURE: Development of PCOS was diagnosed by irregular menses and hyperandrogenism, in the absence of other disorders. Changes in ovarian morphology over time were evaluated. RESULTS: At the baseline visit, 23 women (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM no longer met the criteria for PCOM at follow-up. There was no factor that predicted the change to normal ovarian morphology at the follow-up visit. CONCLUSIONS: These data suggest that PCOM in women with regular ovulatory cycles does not commonly predispose the development of PCOS. Although it is unusual to develop PCOM if the ovaries are normal on first assessment, ovaries in women with PCOM no longer meet the criteria for PCOM in approximately half of cases over time.     

Menstrual patterns and disorders among Chinese women of reproductive age: A cross-sectional study based on mobile application data

Menstruation is an important indicator of women''s health. Identification of abnormal menstrual patterns in adolescence may improve early diagnosis of potential health concerns in adulthood. This study aimed to evaluate menstrual patterns and disorders of Chinese women of reproductive age based on an APP.From December 2015 to January 2016, a cross-sectional study was conducted. We utilized a mobile application (APP) to collect information about participants’ age at menarche, length of menstruation, duration of menstruation, amount of menstrual flow, regularity of menstrual cycle, prevalence of abnormal uterine bleeding and dysmenorrhoea.A total of 156,055 women (25,716 from the questionnaire survey and 130,000 from the mobile APP users) participated in the study. The average age of the subjects was 26.32 ± 6.97 years (median age, 25 years). Mean age at menarche was 13.08 ± 1.87 years; average length of menstrual cycle, 30.9 ± 4.28 days (median 30 days); and average duration of menstruation, 5.01 ± 1.13 days (median 5 days). Women with irregular menstrual cycles accounted for 36.41%. Women aged < 18 years and > 30 years were more likely to experience irregular menstrual cycles. The prevalence of secondary amenorrhoea was 4.07%. More than 20% of women reported abnormal menstrual flow. About 20.11% of women had abnormal uterine bleeding, and 77.65% had dysmenorrhoea. A hot compress was the most commonly used approach to ameliorate dysmenorrhoea. Women with low education and low income and those with high education and high income tended to have menstrual problems.A mobile APP as a survey tool has the advantages of large sample size, low cost, and high efficiency. The use of a mobile APP is an emerging approach for collecting big data in the field of health research. The results showed that the prevalence of menstrual disorders among Chinese reproductive women was high. Healthcare providers should educate girls and their caregivers about menstrual physiology, normal menstrual pattern, and reproductive health to prevent long-term diseases.     

7 Menstrual Dysfunction in Female Dialysis Patients

Introduction Uremia is associated with different endocrinologic abnormalities, which in some cases induce polyendocrinopathia. Female patients on dialysis are often subject to menstrual disorders that are variously manifested. The aim of our paper is to evaluate the etiology of menstrual dysfunctions in female dialysis patients. Material and methods Anamnesis, clinical and hormonal tests were performed on 25 female patients that were in chronic dialysis programs 4 hours, 3 times per week. Oligomenorrhea is considered as menstrual interval between 35 and 90 days and amenorrhea as cease of menstruation in the last six months. Results All patients had had normal menstrual cycles before the dialysis. Mean age of patients was 42.7 ± 9.96 years and mean dialysis duration was 75.5 ± 62.41 months. Out of the 25 patients, 10 developed amenorrhea when beginning dialysis and 5 of them regained regular menstrual cycle after one year. Seven patients had oligomenorrhea and 8 patients had an early menopause. Prolactin concentration was significantly higher in the group which developed menopause (N = 8), c_pr = 1222.3 ± 1013.4, amenorrhea (942.2 ± 1061.2), oligomenorrhea (860.4 ± 897.2), compared to the group with a regular menstruation cycle (444.8 ± 299.7). The luteinizing hormone (LH) level in serum was increased in all groups. FSH was insignificantly higher in groups with oligomenorrhea and amenorrhea and amounted to 51.1 ± 69.9, while β‐estradiol and progesterone were in normal ranges. Hemodialysis duration influenced the prolactin level and after one year of follow up prolactin level significantly decreased in the group with amenorrhea that regained regular menstruation (c_pr = 596.2 ± 297.2). Conclusion Different menstrual disorders are developed in dialyzed patients. Hyper prolactinemia was present in our dialysis population. Significant lowering of prolactin level in 20% of patients led to normalization of menstrual cycle.     

Gonadotropin secretion in bulimia nervosa.

Twenty-two normal weight women with bulimia nervosa (BN) were studied (mean age, 25 +/- 5 yr; body mass index, 20.2 +/- 2.6 kg/m2). Sixteen of them reported menstrual cycles in the range of 21-42 days, and 6 had experienced absence of menstruation for at least 3 months. Twenty-one healthy women with regular menstrual cycles (mean age, 23 +/- 2 yr; body mass index, 20.7 +/- 1.4) served as the control subjects. Frequent morning blood samples for estradiol (E2) and progesterone (P4) determinations were obtained for the duration of 1 menstrual cycle or for 6 weeks in the case of amenorrhea. LH, FSH, cortisol, and insulin secretion were studied on day 3, 4, or 5 after the onset of a menstrual cycle or on a random day in the 6 BN women with amenorrhea. Blood samples were collected at 15-min intervals from 1800-0600 h for LH and FSH and at 30-min intervals from 2400-0600 h for cortisol and insulin. Nineteen of the 21 controls, but only 10 of the 22 BN women, fulfilled the following standard criteria: maximum E2 above 440 pmol/L, maximum P4 above 19 nmol/L, and luteal phase length of 9 days or more. The 10 BN women with normal menstrual cycles had lower mean insulin concentrations than the controls (70 +/- 20 vs. 120 +/- 30 pmol/L; P less than 0.01), but gonadotropin secretion, cortisol, and T3 concentrations were similar. The 8 BN women with amenorrhea or ovulatory dysfunction (maximum E2, less than 440 pmol/L; maximum P4, less than 6 nmol/L) displayed decreased mean LH pulse frequency (2.6 +/- 2.4 vs. 5.7 +/- 2.0 pulses/12 h; P less than 0.01), increased mean cortisol (120 +/- 40 vs. 80 +/- 20 nmol/L; P less than 0.01), decreased mean insulin (90 +/- 40 vs. 120 +/- 30 pmol/L; P less than 0.05), and decreased mean T3 concentrations (1.5 +/- 0.3 vs. 1.8 +/- 0.2 nmol/L; P less than 0.01). The data suggest that BN in normal weight women is associated with an increased rate of ovarian dysfunction; decreased pulsatile LH secretion seems to be an important mechanism. Increased cortisol in the disturbed subgroup indicates that activation of the hypothalamic-pituitary-adrenal axis may play a role in the pathogenesis of gonadal dysfunction in bulimia nervosa.     

Does the menstrual cycle affect anorectal physiology?

It has been shown that during the luteal phase of the menstrual cycle women excrete hard stools and have delayed transit, while at the time of menses, stools are looser and more frequent. The relationship between the menstrual cycle and anorectal physiology, and whether the timing of manometry testing should be standardized within the menstrual cycle has not been previously investigated. In this study, the anorectal responses to balloon distension during days 1–4 (menses), 8–10 (follicular phase), 18–20 (luteal phase) and 24–28 (premenstrual) of the menstrual cycle in 20 healthy female volunteers (ages 18–39 years) was measured. Stools were significantly looser during menses [2.32 (2.1–2.5); mean (95% CI)] compared with the luteal phase [1.98 (1.8–2.2):F(3,30) = 3.1;P<0.04). However, there were no changes in rectal sensitivity, distension-induced rectal motility, rectal compliance, or the volumes required to induce the initial and sustained internal aral sphincter relaxations. In conclusion, although stools become looser at the time of menses, anorectal responses to balloon distension are unaltered. This suggests that the changes in bowel habit associated with the menstrual cycle are unrelated to changes in anorectal physiology. Furthermore, routine manometric testing can be performed at any time during the menstrual cycle without fear of conflicting results.     

Obesity, rather than menstrual cycle pattern or follicle cohort size, determines hyperinsulinaemia, dyslipidaemia and hypertension in ageing women with polycystic ovary syndrome

OBJECTIVE: The aim of this study was to investigate if ageing women with polycystic ovary syndrome (PCOS) who gained regular menstrual cycles differed from women who continued to menstruate irregularly with regard to risk factors for developing diabetes mellitus and atherosclerosis. DESIGN AND PATIENTS: In the original study of a population of 346 PCOS patients, defined in the past as having oligo- or amenorrhoea and elevated LH concentrations, we had sent out a questionnaire to investigate changes in the pattern of their menstrual cycles while ageing. From this cohort of patients, a significantly older group of 53 women (mean age: 41.3 years, range: 33.3-49.4) who were not using oral contraceptives or other hormones visited the outpatient clinic. These women did not differ from the non-participating group in BMI, ethnic origin, the proportion with regular menstrual cycles by age group, parity or the use of clomiphene citrate or gonadotrophins in the past. MEASUREMENTS: A physical examination and a transvaginal ultrasound were performed. The size of the follicle cohort was determined by counting the number of small follicles in the ovaries. Thirty-four women were also willing to give two fasting blood samples for measuring their glucose, insulin and lipid status. RESULTS: Forty-one of the 53 (77.4%) women had a regular menstrual cycle (shorter than 6 weeks) and 12 (22.6%) had an irregular cycle (longer than 6 weeks). The body mass index (BMI), waist: hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and prevalence of diabetes (1-9%) and hypertension (11.3%) did not differ between the two menstrual cycle groups. Also, the fasting glucose, insulin, glucose/insulin ratio, total cholesterol, HDL-c, and LDL-c concentrations did not show any significant difference between the two groups. Instead, these parameters all were significantly higher in women with a BMI > 27 kg/M2 compared to women with a BMI < or = 27 kg/m2. Regularly menstruating PCOS women were older (P < 0.01), showed less follicles in their ovaries (n = 48, P < 0.01) and had lower androgens (n = 34, P < 0.05) than the irregularly menstruating women. Logistic regression analysis showed a second significant influence, after age, of the BMI on the menstrual cycle pattern (age, P < 0.01; BMI, P < 0.05). If age was excluded from the analysis, only the follicle count significantly predicted the menstrual cycle pattern (P < 0.02). CONCLUSIONS: We conclude that hyperinsulinaemia, dyslipidaemia and hypertension in our population of ageing women with polycystic ovary syndrome are not related to the menstrual cycle pattern but rather to obesity. Age and the size of the follicle cohort are the main factors determining the menstrual cycle pattern in ageing women with polycystic ovary syndrome, although an association with the BMI was also found.     

Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.     

Menstrual cycle and exposure to oestrogens unopposed by progesterone: relevance to studies on breast cancer incidence

It is claimed that the exposure of women to oestrogens unopposed by progesterone increases the risk of breast cancer. Despite indirect evidence in support of this claim, the impracticability of monitoring oestrogen and progesterone levels in large numbers of women for prolonged periods of time has meant that no direct demonstration of the effect has been made. A possible technique is suggested. The ratio (R) of oestrogens to pregnanediol in urine has been used as an index of oestrogen exposure relative to progesterone. Samples were collected at weekly intervals on 700 occasions from 30 perimenopausal women, and on 519 occasions from 66 women with a history of regular menstrual cyclicity. Unusually prolonged episodes of unopposed high oestrogen excretion (R greater than or equal to 100 for greater than or equal to 2 successive weeks) were observed on 30 occasions in 15 of the perimenopausal women and on four occasions in the other women. In the perimenopausal group, these episodes occurred in 46.9% of the 32 menstrual cycles which were longer than 50 days compared with 6.9% of the 72 cycles which were shorter than 35 days (P less than 0.001). The association of prolonged episodes of unopposed high oestrogen excretion with long menstrual cycles suggests the possibility of using menstrual cycle length as an index of oestrogen exposure during the menopausal transition.     

Late luteal phase administration of RU486 for three successive cycles does not disrupt bleeding patterns or ovulation

RU486, a 19-nor steroid, binds with high affinity to the receptors for progesterone and glucocorticoids, blocking the actions of these hormones on their target tissues. We conducted studies to determine whether RU486 administered at the end of the luteal phase would disturb the menstrual rhythm, ovulation, or hormonal parameters in the treatment and post-treatment cycles. The first study was done in six surgically sterilized women during two consecutive cycles. RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(1-propynyl)estra-4,9-dien-3-one; 100 mg/day] was given for 4 consecutive days, commencing on days 23-27 of the first cycle. Menstrual bleeding occurred by the second day of RU486 administration in all women and was indistinguishable from their usual bleeding pattern. The onset of this bleeding was advanced by RU486 administration, since it entailed shortening of the luteal phase with prolongation of the following follicular phase. Serum LH, FSH, estradiol, and progesterone levels were normal in five of the six women in both the treatment and posttreatment cycles. The second study was conducted in 10 women who were not exposed to the risk of pregnancy. RU486 (100 mg/day) was given for 4 consecutive days, commencing 4 days before their expected menses for 3 successive cycles, preceded and followed by 2 placebo-treated cycles. Bleeding patterns were indistinguishable during the RU486 and placebo cycles. Late luteal phase administration of RU486 consistently produced menstrual bleeding within 1-3 days of drug administration. Daily early morning urinary LH excretion in 6 women and estrone glucuronide and pregnanediol glucuronide excretion in 5 women during both placebo and RU486 cycles were consistent with luteinization, suggesting ovulation and appropriate corpus luteum function. We conclude that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.     

Follicular fluid treatment during the follicular versus luteal phase of the menstrual cycle: effects on corpus luteum function

Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys at the time of menses impairs the subsequent function of the corpus luteum of the menstrual cycle. The following studies were performed: 1) to characterize the luteal phase defect induced by pFF treatment at menses, and 2) to determine whether pFF treatment in the luteal phase alters corpus luteum function. Adult, female rhesus monkeys were injected sc for 3 days with pFF (10, 5, and 5 ml) beginning on day 1 (n = 5) or day 18 (n = 4) of the menstrual cycle. Femoral venous blood was collected daily throughout the treatment cycle and during the posttreatment cycle of day 18 to 20-treated monkeys. Serum LH, FSH, 17 beta-estradiol (E2), and progesterone (P) were measured by RIA. After pFF treatment on days 1-3, FSH and E2 levels in the early follicular phase were less (P less than 0.05) than those of control cycles (n = 7). Serum LH was not suppressed by pFF treatment. Moreover, the preovulatory rise in circulating E2 and the amplitude of the LH/FSH surge were similar in control and pFF-treated monkeys. Although timely midcycle gonadotropin surges occurred in four of five pFF-treated monkeys, serum P was markedly reduced (P less than 0.05) during the first half of the luteal phase. Circulating P increased to control levels during the late luteal phase before normal onset of menses 16.3 +/- 1.0 (SE) days after the LH surge. Treatment with pFF on days 18-20 of the cycle reduced the levels of circulating FSH, but serum LH, E2, P, and the length of the luteal phase remained comparable to control cycles. Moreover, the hormonal patterns and the length of the follicular and luteal phases in the posttreatment cycle indicated normal ovarian function. Thus, pFF treatment at menses results in an aberrant ovarian cycle characterized by an insufficient, rather than short, luteal phase. Whereas pFF treatment in the early follicular phase vitiates development of the dominant follicle and the related corpus luteum, similar treatment at midluteal phase does not suppress concurrent luteal function or subsequent folliculogenesis.     

A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release

AIMS: This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. DESIGN: A three-group randomized controlled trial was conducted between September 2003 and June 2005. SETTING: A Baltimore pre-release prison. PARTICIPANTS: Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. INTERVENTION: Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). MEASUREMENTS: Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. FINDINGS: Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. CONCLUSIONS: Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.     

Concentrations of oestradiol-17beta and progesterone in the peripheral plasma of the cynomolgus monkey (Macaca fascicularis) in relation to the length of the menstrual cycle and its component phases.

Ninety-three female cynomolgus monkeys were monitored throughout 647 menstrual cycles; 93.2% of these cycles were 22--37 days long and were normally distributed, with a mean of 29.2 days. Menstrual bleeding generally lasted for 3--5 days and was not related to the length of the cycle. The levels of progesterone and oestradiol-17beta in the plasma were measured during the menstrual cycle in 30 monkeys. The concentration of oestradiol-17beta reached a mid-cycle peak on day 11 or 12 of the cycle. The interval between the beginning of the cycle and the oestrogen peak was constant; the interval between the oestrogen peak and the end of the cycle increased or decreased with the cycle length. The level of progesterone began to rise at about the time of the oestrogen peak and remained raised for longer periods as the length of the cycle increased. The length of the menstrual cycle, therefore, appeared to be determined by the duration of the increase in the level of progesterone or by the life of the corpus luteum in the luteal phase. The relationship between the lengths of the cycle and the luteal phase can be defined by the expression: cycle length = 12.6 + 0.96 X length of luteal phase (correlation coefficient = 0.875).     

The influence of dieting on the menstrual cycle of healthy young women

Nine normal young women of normal weight, aged 20-29 yr, who had regular menstrual cycles, dieted for 6 weeks (approximately 800-1000 kcal/day) and lost between 6 and 8 kg body wt. Half-hourly blood samples were taken from 1800-0530 h on two occasions before and after 1, 2, 3, 4, 5, and 6 weeks of dieting. In three women with anovulatory cycles the LH secretion pattern was not altered by dieting, but plasma estradiol levels decreased and reached menopausal concentrations during the final 2 weeks of dieting. In two of these three women the menstrual cycles were disrupted and regular cycles occurred only 3 and 6 months after dieting. Six women had regular ovulatory cycles. High progesterone values (greater than 3 ng/ml) were recorded in two cycles before the dieting period. While dieting, three women maintained ovulatory cycles and three women had no periovulatory hormone secretion pattern and/or a pattern characteristic of the luteal phase. No significant alterations of average LH concentrations and LH peak frequency developed. It is concluded that mild dieting does not suppress LH secretion in the manner found in anorexia nervosa or during total fasting. Dieting may interfere with gonadal steroid production, thus causing disturbances of the menstrual cycle. The effect described here may be responsible for the early onset of amenorrhea in patients with beginning anorexia nervosa.     

The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.

Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.     

Racial differences in menopause information and the experience of hot flashes

OBJECTIVE: To compare the prevalence of hot flashes and health education regarding menopause in African-American and white American women in the late reproductive years.
DESIGN: Cross-sectional study.
SETTING: Population-based sample recruited through random digit dialing.
PARTICIPANTS: The sample was 436 women between the ages of 35 and 48 years with regular menses. Half the sample was African American and half was white American.
MAIN RESULTS: African-American women (53%) were more likely than white American women (29%) to have experienced hot flashes (p < .001). The difference remained after adjustment for body-mass index, education, menstrual cycle characteristics, and gynecologic and medical history. Despite the high prevalence of symptoms, few women had discussed menopausal management with their physicians. For white women the media were the primary source of menopause-related information, whereas African-American women reported that their family was the primary source of information.
CONCLUSIONS: These results indicate that hot flashes occur commonly among women in their thirties and forties who have regular menstrual cycles and that the prevalence of hot flashes appears to differ by race. Studies should be designed to evaluate the hormonal and physiologic implications of these symptoms among women in their late reproductive years. Few of these women had discussed menopause with their physicians. Given the differences in sources of information about menopause, development of culture-specific health education programs should be considered.