Changes In Menstrual Cycle Length Research Articles

Endocrine Features of Menstrual Cycles in Middle and Late Reproductive Age and the Menopausal Transition Classified According to the Staging of Reproductive Aging Workshop (STRAW) Staging System

Female reproductive aging based on changes in menstrual cycle length and frequency progresses through a number of stages as defined by the Stages of Reproductive Aging Workshop (STRAW) staging criteria. This paper provides a comprehensive description of the endocrine features associated with the STRAW stages. Healthy women aged 21-35 and 45-55 yr submitted three blood samples a week over a single menstrual cycle. They were classified as mid-reproductive age (n = 21), late-reproductive age (n = 16), early menopause transition (n = 16), and late menopause transition (n = 23). There were nine, one, zero, and two anovulatory cycles identified in the late menopause transition, early menopause transition, late-reproductive age, and mid-reproductive age groups, respectively. Ovulatory cycle FSH, LH, and estradiol levels increased with progression of STRAW stage (P = 0.001, P < 0.01, and P < 0.05, respectively), and mean luteal phase serum progesterone decreased (P < 0.01). Early cycle (ovulatory and anovulatory) inhibin B decreased steadily across the STRAW stages (P < 0.01) and was largely undetectable during elongated ovulatory and anovulatory cycles in the menopause transition. Anti-Mullerian hormone decreased markedly (10- to 15-fold) and progressively across the STRAW stages (P < 0.01 and P < 0.001, respectively). Progression through the STRAW stages is associated with elevations in serum FSH, LH, and estradiol and decreases in luteal phase progesterone. The marked fall in inhibin B and particularly anti-Mullerian hormone indicate that they may be useful in predicting STRAW stage but future analyses of early cycle measurements on larger cohorts are needed to draw predictive conclusions.

Menstrual bleeding patterns following levonorgestrel emergency contraception

Purpose Multiple trials by the World Health Organization have established levonorgestrel as the gold standard in hormonal emergency contraception (EC). However, changes in menstrual patterns following EC have been observed; thus, we undertook this prospective study to identify and determine the characteristics of these changes. Materials Women requesting EC at either any of two hospitals — 1 family planning unit and 12 pharmacies in Yaoundé, Cameroon were enrolled if they had a history of regular menstrual cycles over the previous 3 months and if they agreed to follow-up until the end of the subsequent menstrual cycle. Pretreatment menstrual patterns were compared with those of the EC treatment cycle and the cycle after EC. Results In a set of 232 participants (mean age, 25 years), we observed 34 (14.7%) cases of incident intermenstrual bleeding and statistically significant changes in menstrual cycle length, menstrual period length and menstrual appearance compared to baseline patterns that differed according to whether EC was taken well before, close to or well after the expected ovulation for that cycle. The majority of these changes disappeared in the following cycle. Conclusion Levonorgestrel EC is associated with significant but transient changes in menstrual patterns in a significant proportion of users.

Developing a Model of Nutritional Amenorrhea in Rhesus Monkeys

Nutritional amenorrhea is defined as cessation of menstrual cycles resulting from a chronic negative energy balance. Although it is agreed that nutritional amenorrhea results from reduced secretion of GnRH, the neuroendocrine mechanisms leading to GnRH inhibition are poorly defined. Because the invasiveness of many neuroendocrine experimental approaches precludes its use in the clinical setting, we set out to establish a model of nutritional amenorrhea in rhesus monkeys. Studies were conducted in four normal-weight and one obese female rhesus monkey. Dietary intake was gradually reduced with the goal of achieving a 15-20% weight reduction. Dietary restriction inhibited ovulation in all animals. The weight loss required to inhibit ovulation ranged from 2-11% in the four normal-weight animals and was achieved with a 23% reduction in dietary intake. The time of initiating reduced food intake to first missed ovulation was 62 +/- 13 d. Greater weight loss (46% reduction) over a longer period (10 months) was required to inhibit ovulation in the obese monkey. The onset of anovulation was not preceded by changes in menstrual cycle length or progesterone secretion. Realimentation initiated ovulation at a weight that approximated the animal's weight at the time of the last ovulatory cycle during dietary restriction. By contrast, caloric intake at the return of ovulation during realimentation was 28% greater. This is the first demonstration that chronic dietary restriction can inhibit ovulation in rhesus monkeys. This model will be useful for studying the neuroendocrine mechanisms involved in diet-induced anovulation in primates.

Defining menopause status: creation of a new definition to identify the early changes of the menopausal transition

Several menopausal staging definitions are currently being used in ongoing studies designed to identify changes occurring during menopause. The objective of this study was to determine which definition captures the earliest hormonal changes in the menopausal transition. In this prospective cohort study, women aged 35 to 47 years were followed for 5 years. Women were classified as premenopausal, early transition, late transition, and postmenopausal by 2 different menopausal staging systems defined by bleeding patterns. Definitions from the Study of Women Health Across the Nation (SWAN) and Stages of Reproductive Aging Workshop (STRAW) were compared. A new menopausal staging system (PENN-5) was also developed with five groups rather than four to distinguish among women with more subtle changes in cycle length. For each staging system, a linear regression model was created comparing mean hormone values (inhibin B, FSH, LH, E2) and menopausal stages at each assessment. Race, body mass index, cycle day, smoking, and follow-up time were included in the model. Statistically significant differences in mean inhibin B and FSH levels, but not estradiol levels, were detected between the earliest menopausal stages of each definition. Significant differences in LH values were detected among the earliest stages of the SWAN and STRAW definitions, but not the PENN-5 definition. Subtle changes in menstrual cycle length reflect significant changes in inhibin B and FSH levels during the menopausal transition. Therefore, it appears that subtle changes in bleeding pattern may be helpful in identifying the earliest hormonal changes during menopausal transition.

Ovulation Block by &lt;I&gt;Pueraria mirifica&lt;/I&gt;: A Study of Its Endocrinological Effect in Female Monkeys

Pueraria mirifica (PM), a Thai herb containing phytoestrogens, may act as estrogen and disturb reproduction. To investigate the effect of PM on the menstrual cycle length and related hormones, nine adult female monkeys (Macaca fascicularis) were separated into three groups. Each group (n = 3) was fed with 10, 100, and 1000 mg/d of PM for three menstrual cycles. The menstrual cycle length increased significantly in monkeys treated with PM-10 and PM-100 and disappeared completely in monkeys treated with PM-1000. Serum follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, and irinhibin were lower during the treatment period in a dose-dependent manner. Changes in menstrual cycle length and the hormonal levels recovered during the post-treatment period only in monkeys treated with PM-10 and PM-100. PM greatly influences menstrual cycles and may suppress ovulation by lowering serum levels of gonadotropins.

Estrogenic Effects of Pueraria mirifica on the Menstrual Cycle and Hormone-Related Ovarian Functions in Cyclic Female Cynomolgus Monkeys

This study investigated the estrogenic effect of Pueraria mirifica (P. mirifica) on menstrual cycle length and hormone-related ovarian function. Nine normal cyclic monkeys (Macaca fascicularis) were separated into 3 groups; each group was force fed with a single dose of 10, 100, and 1,000 mg of P. mirifica. The experimental schedule was separated into the pre-treatment and post-treatment periods. Blood samples were collected on days 3, 9 – 14, 19, 24, 29, and every 10 days until the next menstruation for one and two menstrual cycles during two consecutive periods and assayed for serum levels of gonadotropins and ovarian hormones. The result showed a significant increase in lengths of the follicular phase and total menstrual cycle in monkeys treated with 1,000 mg of P. mirifica, but no change in menstrual cycle length in monkeys treated with 10 and 100 mg of P. mirifica. Serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, or immunoreactive-inhibin did not change during the first and second menstrual cycles of the post-treatment period for all monkey groups. Our findings demonstrate that although changes in hormonal levels could not be observed in this study, a single dose of 1,000 mg of P. mirifica can disturb ovarian function and menstrual cycle in monkeys.

Effects of Soy Intake on Sex Hormone Metabolism in Premenopausal Women

Studies suggest that phytoestrogens in soy products may impart hormonal effects that protect women against breast cancer. Limited research suggests that intake of soy products high in isoflavonoid phytoestrogens affects sex hormone metabolism, but it is unknown whether phytoestrogens in soy have any effect on menstrual function or serum sex hormones in women on common hormone therapies, such as oral contraceptives (OC). We studied the effects of soy in 36 premenopausal women, 20 of whom used OC. Subjects consumed their normal diet for two menstrual cycles and added a soy beverage containing 20 g of protein and 38 mg of total isoflavones to their usual diet for another two menstrual cycles. No significant differences were observed in serum estrone, estradiol, sex hormone-binding globulin, dehydroepiandrosterone sulfate, prolactin, or progesterone concentrations with soy feeding in the non-OC or the OC group. No changes in menstrual cycle length or the urinary estrogen metabolite ratio of 2-hydroxyestrone to 16α-hydroxyestrone were seen with soy feeding in the non-OC or the OC group. Levels of urinary estrogen metabolites were significantly different between the non-OC and the OC group. Thus soy consumption had no significant effect on the menstrual cycle, serum sex hormones, or urinary estrogen metabolite ratio in premenopausal OC or non-OC users.

Effect of fluoxetine on menstrual cycle length in women with premenstrual dysphoria

To examine whether changes in menstrual cycle length occurred in women who received 20 mg of fluoxetine per day and women who received 60 mg of fluoxetine per day as compared with women who received placebo. A two-cycle, single-blind placebo phase was followed by a six-cycle double-blind phase. Only placebo nonresponders were randomized to one of three treatment arms: placebo, fluoxetine 20 mg/day, or fluoxetine 60 mg/day. Cycle length was established using a prospective daily calendar. Cycle-length data from women who completed at least three treatment cycles were used in this analysis. Cycle-length change was defined a priori as cycle lengthening or shortening of 4 days or more (1 or more standard deviations from the mean change between baseline cycles). Eleven of the 62 women receiving 60 mg of fluoxetine per day and seven of the 70 women receiving 20 mg of fluoxetine per day but only one of the 61 women in the placebo group demonstrated cycle-length change at the end of the first treatment cycle (P = .011). In total, 15% of the women in the fluoxetine 60 mg/day group demonstrated a cycle-length change during two of the three observed cycles compared with 6% of the women in the fluoxetine 20 mg/day group and 3% of the women in the placebo group (P = .048). Women with cycle-length changes demonstrated either shortening or lengthening only. There were no differences between the number of women with changes in either direction. Cycle-length change occurred more frequently in the fluoxetine 60 mg/day group than in the fluoxetine 20 mg/day or placebo groups. The effects of selective serotonin reuptake inhibitors on menstrual cycle length are mostly unknown and warrant careful monitoring in women of reproductive age, who are the prime consumers of these medications.

Effects of a very low fat, high fiber diet on serum hormones and menstrual function implications for breast cancer prevention

Low fat, high fiber dietary interventions that decrease blood estrogen levels may reduce breast cancer risk. Asian women consuming their traditional low fat, high fiber diets have lower blood estrogen levels before and after menopause and lower rates of breast cancer compared with Western women. The current controlled feeding study of premenopausal women was designed to determine the effects of a very low fat (10% of calories) and high fiber (35-45 g/day) diet on blood estrogen levels and menstrual function. Twelve healthy premenopausal women with regular ovulatory cycles were followed for 3 months. Subjects consumed a diet providing 30% of their energy from fat and 15-25 g of dietary fiber per day for 1 month, and they consumed a very low fat, high fiber and libitum diet providing 10% of their energy from fat and 25-35 g of dietary fiber per day for 2 months. At the end of the second month of the very low fat, high fiber diet, there was a significant reduction in serum estrone and estradiol levels during the early follicular and late luteal phases. There were no significant changes observed in serum estrone sulfate, sex hormone binding globulin, or progesterone. Despite a significant decrease in serum estradiol and estrone levels after 2 months of a very low fat, high fiber diet, there was no interference with ovulation or the magnitude of the mid-cycle leuteinizing hormone surge. Small changes in menstrual cycle length of up to 3 days were not ruled out due to the small sample size of the study. A very low fat, high fiber diet in healthy premenopausal women can reduce estradiol and estrone levels without affecting ovulation, thereby providing a rationale for the prevention of breast cancer through a very low fat, high fiber diet.

Alterations in circulating ovarian steroids in hexachlorobenzene-exposed monkeys

Hexachlorobenzene (HCB) is a global pollutant that has been identified in human serum and ovarian follicular fluid, and its effect on ovarian function has not been adequately defined. Thus, the effects of HCB on ovarian steroidogenesis and menstrual cycle characteristics were investigated in cynomolgus monkeys ( n = 16) orally dosed by gelatin capsule (0.0, 0.1, 1.0, and 10.0 mg HCB/kg b.wt./d) for 90 d (approximately three menstrual cycles). Analysis of change in menstrual cycle length for each animal revealed a dose-dependent increase ( P = 0.02) in cycle length. Ovulatory levels of estradiol (E 2) were significantly reduced ( P = 0.02) in the highest treatment group. During ovulation induction, the area under the E 2 concentration curve (AUC) was significantly ( P = 0.03) suppressed in the highest treatment group. Our data demonstrate that HCB treatment, under the conditions of the present study, alters both ovarian function and menstrual cycle characteristics with a no observable adverse effect level of 1.0 mg/kg.

Menstrual disorders and pelvic pain after sterilization

Changes in menstrual cycle length, menstrual duration, number of pads, dysmenorrhea and non-cyclic pelvic pain were studied in 43 women following tubal sterilization with three different techniques. One group consisted of 17 women undergoing laparotomy by Pomeroy technique; the second group consisted of 11 women undergoing laparoscopy by Fallope rings; and the third group consisted of 15 women undergoing colpotomy by fimbriectomy. The differences before and after sterilization in cycle length were non-significant in all groups (p > 0.05). After sterilization, menstrual duration and number of pads were significantly increased in the laparotomy (p < 0.001) and laparoscopy (p < 0.01) groups but non-significantly in the colpotomy group (p > 0.05). Comparison of these parameters between the groups did not show any significant differences (p > 0.05). After sterilization, increases in the severity of dysmenorrhea and non-cyclic pelvic pain were non-significant in all groups (p > 0.05). We concluded that there were no significant differences in menstrual disorders after sterilization among these three different techniques.

Changes in menstrual cycle length and regularity after use of oral contraceptives.

This is an analysis of changes in menstrual cycle length and regularity occurring for a group of 211 women who had discontinued use of oral contraceptives. The analysis is based on prospectively recorded histories from the Menstruation and Reproduction History Program. Post-pill menstrual cycle length and regularity are compared with pre-pill averages. In the first post-pill cycle, there was an average increase of 6 days in cycle length. In subsequent cycles, however, cycle length and regularity were comparable to pre-pill norms in most cases.