Semiparametric regression for periodic longitudinal hormone data from multiple menstrual cycles

We consider semiparametric regression for periodic longitudinal data. Parametric fixed effects are used to model the covariate effects and a periodic nonparametric smooth function is used to model the time effect. The within-subject correlation is modeled using subject-specific random effects and a random stochastic process with a periodic variance function. We use maximum penalized likelihood to estimate the regression coefficients and the periodic nonparametric time function, whose estimator is shown to be a periodic cubic smoothing spline. We use restricted maximum likelihood to simultaneously estimate the smoothing parameter and the variance components. We show that all model parameters can be easily obtained by fitting a linear mixed model. A common problem in the analysis of longitudinal data is to compare the time profiles of two groups, e.g., between treatment and placebo. We develop a scaled chi-squared test for the equality of two nonparametric time functions. The proposed model and the test are illustrated by analyzing hormone data collected during two consecutive menstrual cycles and their performance is evaluated through simulations.     

Sexual behavior and hormone levels during the menstrual cycles of rhesus monkeys.

The sexual interactions of 10 pairs of rhesus monkeys were observed during a control and an experimental menstrual cycle of each female. During the experimental cycle the females were treated with an antiandrogen, flutamide. Daily peripheral serum levels of estradiol, testosterone, and progesterone in each female were determined by radioimmunoassay. Sexual behavior did not correlate reliably with female serum concentrations of any hormone measured nor with the menstrual cycle stage. Administration of the antiandrogen to the females did not affect the sexual behavior of the pairs, although female serum levels of estradiol and testosterone were reduced. It was concluded that although female ovarian hormones may influence rhesus sexual interactions under some circumstances, the normal hormonal fluctuations during the menstrual cycle need not regulate this behavior; a knowledge of an intact rhesus female's hormonal condition does not allow accurate predictions about behavior displayed during laboratory pair tests with a male.     

Sexual behavior and urinary ovarian hormone concentrations during the lowland Gorilla menstrual cycle

Sexual behaviors were recorded and urinary concentrations of total estrogens and pregnanediol-3-glucuronide (Pdg) measured during six normal menstrual cycles from two female lowland gorillas in a stable, captive group. Frequencies of female presentations, mounts, and copulations were positively associated with peak estrogen values but not with elevations of Pdg. These results support the observation that sexual behaviors in the gorilla occur most frequently in the periovulatory period and that copulations serve primarily a sexual function.     

Women do not synchronize their menstrual cycles

It is widely believed that women who live together or who are close friends synchronize their menstrual cycles. We reexamined this phenomenon in two ways. First, we collected data on menstrual cycles from 186 Chinese women living in dorms for over a year. We found that women living in groups did not synchronize their cycles. Second, we reviewed the first study reporting menstrual synchrony. We found that group synchrony in that study was at the level of chance. We then show that cycle variability produces convergences and subsequent divergences of cycle onsets and may explain perceptions of synchrony. This study was supported by the Sichuan Youth Foundation of Science and Technology (Chuan Ke Ji [2001] 2) and NIH Grant No. 5R01MH065555-02. We thank Shuhuan Yang, Xia Xu, Jun Qu, Jing Zhu, Meijia Yu, & Chang Zhou for all their work in collecting the data. Without them, this study could never have been done. Zheng-Wei Yang is director and professor of the Morphometric Research Laboratory, North Sichuan Medical College, China. His main research interests are in spermatogenesis, morphometry, and stereology. Jeff Schank is associate professor of psychology at the University of California, Davis. His main research interests are in computational and biorobotic modeling of group behavior and the development of sensorimotor behavior in animals.     

Effect of dexamethsone on luteinizing hormone and follicle stimulating hormone responses to LHRH and to clomiphene in the follicular phase of women with normal menstrual cycles.

In an attempt to elucidate the mechanism of suppressive action of glucocorticoids on the hypothalamo-pituitary-ovarian axis, we studied the effects of short-term high dose dexamethasone administration of the LH and FSH responses to LHRH and to clomiphene in healthy women with normal menstrual cycles. Seven women, 21--35 years of age, received 100 micrograms of LHRH i.v. on day 6 of two consecutive menstrual cycles, once with and once without pre-treatment with dexamethasone 2 mg orally every 6 hrs. on days 2 through 5 of the menstrual cycle. Seven other women (ages 21--35 years) received clomiphene citrate 100 mg on days 2 through 5 of their menstrual cycle, once with and once without simultaneous administration of dexamethasone 2 mg orally every 6 h. The administration of dexamethasone suppressed baseline serum levels of LH and FSH and blunted LH and FSH response to both LHRH and clomiphene. The results indicate that short-term administration of pharmacological doses of glucocorticoids suppress the secretion of LH and FSH by a direct effect on the anterior pituitary and possibly by an effect at the hypothalamic level with inhibition of the release of LHRH.     

Copper levels in cervical mucus during normal menstrual cycles

To establish the pattern of copper levels in cervical mucous, individual samples were taken from 10 normal women (aged 23-46), 2-3 times per week during the cycle. Analysis using a modification of the Stoner and Dasler wet ash microtechnique showed the lowest amounts of copper per 100 mg of dried ash (mean-3.2 mcg) in the ovulatory phase. The highest amount of copper was found in the secretory phase (mean 19.4 mcg). The copper level seemed to vary directly with the level of endogenous progesterone and inversely with the level of endogenous estrogen. No significant correlation between age and amount of copper secreted could be established because of the small size of the study.     

Photoperiod and ovulatory menstrual cycles in female macaque monkeys

Macaques (Macaca mulatta and M. assamensis) which had been maintained on a 12L :12D light cycle for the previous 4 years and had 25-35-day menstrual cycles were randomly assigned to two groups. Those in Group 1 were kept in 12L :12D for 13 months. Those in Group 2 were subjected to three successive 5-month periods of 20L :4D, 4L :20D and 20L :4D. There were no significant differences between the two groups in the frequency, duration and percentage of ovulatory menstrual cycles, suggesting that photoperiod is not the sole regulator of seasonal breeding in these animals.     

Female axillary secretions influence women''s menstrual cycles: A critique

Preti, Cutler, Garcia, Huggins, and Lawley report (1986, Horm. Behav. 20, 474-482) that women's menstrual cycles can be modulated with applications of female-derived secretions. An experimental sample of 10 women who reported that they had 29.5 +/- 3 day menstrual cycles was treated on a 22- to 25-day cycle with an extract of axillary secretions from a group of female donors. After two menstrual cycles, the mean absolute difference between the women's menses onsets and the treatment applications decreased significantly. A control sample of 9 women similarly treated with blank/ethanol showed no significant change. Reanalysis of the data indicates that four subjects in the extract sample synchronized with the extract cycles because of "errors" in the extract applications and another four synchronized as a result of experimental design, mathematical properties of cocycling menses onsets, and chance variations. After these factors are accounted for, no evidence suggests that the cycles of the subjects in the extract sample were modulated by the female-derived axillary secretion.     

Male axillary secretions influence women's menstrual cycles: a critique

W. B. Cutler et al. report in the December 1986 issue of Hormones and Behavior (20, 463-473), that women treated with axillary extract from male donors showed reduced variability in menstrual cycle lengths and a reduced proportion of aberrant cycles. The initial samples--seven subjects treated with the male extract and nine subjects treated with blank/ethanol--did not differ significantly in the frequency of aberrant and normal cycles. The cycles of four subjects who were having weekly coital activity were removed from the samples, since coital activity has been shown to be associated with normal-length cycles. The frequency differences of aberrant and normal cycles in the reduced extract and placebo samples were statistically significant. The experiment's conclusions are questionable because (1) the decision to remove the cycles of the four women who had weekly coital activity was not justified by the evidence from this experiment and (2) the researchers lacked an observed preexperimental data base from which to measure changes in the women's cycle lengths.     

Plasma gonadotrophin and ovarian steroid concentrations in women with menstrual cycles with a short luteal phase

Daily plasma concentrations of FSH, LH, oestradiol-17 beta and progesterone were compared for 12 cycles with a short luteal phase and 19 cycles with a luteal phase of normal length (i.e. cycles in which the luteal phase lasted 12 or more days). FSH and LH concentrations were suppressed in short luteal-phase cycles in the early follicular phase and the length of the follicular phase was prolonged (median duration, 14.5 days, range 13-21 days: compared with 12 days, range 9-17, in control cycles; P less than 0.025). Preovulatory oestradiol-17 beta values and the mid-cycle concentrations of FSH and LH were similar in both groups. Plasma progesterone values in the luteal phase were similar in both groups over the 2nd to 5th days inclusive after the midcycle LH peak but declined in the short luteal phases thereafter. In short luteal-phase cycles, menstruation occurred in the presence of higher levels of oestradiol-17 beta and progesterone than in cycles of normal length and the rise of gonadotrophin in the late luteal phase of the cycle was delayed. These findings suggest that in cycles with a short luteal phase there is a lack of synchrony between the ovarian and menstrual events.     

Endocrine characteristics of adolescent menstrual cycles: impact of early menarche

An initial group of 200 girls, 7-17 years old, was investigated longitudinally 4 times at 1.5-, 1.5- and 5-year intervals. The present study gives information of the impact of early menarche, a risk factor for breast cancer, on some physical and endocrine characteristics in these subjects. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche. Early menarche was associated with early onset of ovulatory cycles. Even in early puberty, before menarche, the subjects who displayed early menarche during follow-up had higher serum FSH and estradiol concentrations than the girls whose menarche took place after the age of 13.0 years. Adrenal androgen secretion (dehydroepiandrosterone) was not influenced by age at menarche but it increased, as expected, on the basis of chronological age. The group with early menarche was characterized by high circulating estradiol concentrations also after menarche, even in the oldest subjects so far studied, 17-25 years of chronological age. At these ages, the differences in the frequencies of ovulatory cycles were disappearing between the groups formed on the basis of age at menarche. The present findings in pre- and postmenarcheal subjects suggest that the increased risk of breast cancer associated with early menarche is created over several years of exposure to high-level estrogen stimulus.