Raymond L. Vande Wiele

Regulation of the human menstrual cycle

The new data available on the morphologic and hormonal changes during the normal menstrual cycle are presented and this information is integrated into a comprehensive model that accounts for the main events of the menstrual cycle and for its cyclic nature. The morphologic changes during the cycle are broken down into phases: 1) Phase 1 the initial follicular growth; 2) Phase 2 follicular maturation and atresia; 3) Phase 3 the ovulatory period; 4) Phase 4 luteinization and the corpus luteum. The hormonal changes are described for these same phases. An engineering analysis of the menstrual with the use of nonlinear algebraic and differential equations to state explicitly the behavior of each hormonal and morphologic component of the cycle is presented. By this means the dynamic response of all components in the cycle can be rapidly analyzed in order to test the effects of various hypotheses on the total system.

The use of human menopausal and chorionic gonadotropins for induction of ovulation

Gonadotropin therapy for anovulation is highly successful: 58.6% of treated patients conceive. Better results are achieved in patients with galactorrhea-amenorrhea (77.1%) and hypogonadotropic hypogonadism (63.3%) than in patients with normal gonadotropin levels (45.4%). The spontaneous abortion rate (27.5%) is somewhat higher than that in spontaneous pregnancies. The multiple pregnancy rate is 31% and was slightly lower in cycles with preovulatory estrogen levels in the physiologic range. In patients treated with human menopausal and chorionic gonadotropins for 7 to 9 days per cycle, the multiple pregnancy rate is considerably less (12.9%) than in patients with longer treatment. The efficacy of treatment does not diminish with repeat-treatment cycles.

17 α-HYDROXYPROGESTERONE AND 21-DESOXYHYDROCORTISONE; THEIR METABOLISM AND POSSIBLE ROLE IN CONGENITAL ADRENAL VIRILISM 1

Although virilism due to bilateral adrenal hyperplasia is a relatively rare condition, this syndrome has stimulated much interest and research. Previous work has demonstrated that the adrenals of patients with this disease respond differently from the normal when they are further stimulated with exogenous ACTH. Lewis and Wilkins (1), Bartter and his associates (2), and Jailer, Louchart, and Cahill (3) have shown that although

Food intake and the menstrual cycle in rhesus monkeys

Abstract Fourteen adult female rhesus monkeys were observed for 1 complete menstrual cycle, five of them for 2 cycles. Changes in LH, FSH, estrogens and progesterone were monitored daily. Mean hormonal concentrations followed patterns previously demonstrated in primates, with a typical late follicular phase estrogen peak preceeding the ovulatory LH and FSH surges. Maximal sexual skin color intensity paralleled the midcycle increase in estrogens. The results indicate that food intake fluctuated with changes in hormonal secretion. A significant decrease in the amount of food consumed correlated well with the midcycle estrogen and gonadotropin surges. The amount of food consumed during the luteal phase was greater than that of the early follicular phase.

Hypothalamic-pituitary-adrenal-cortical activity in anorexia nervosa and bulimia

We studied hypothalamic-pituitary-adrenal-cortical (HPA) activity in nine underweight women with anorexia nervosa, 12 women of normal body weight with bulimia, and nine control subjects. The measures of HPA activity were the pattern of plasma cortisol secretion over 24 hr and the responses of plasma cortisol to dexamethasone suppression and to low dose ACTH stimulation. The patients with anorexia nervosa had significantly elevated 24 hr concentrations of plasma cortisol compared to the controls and showed significantly less cortisol suppression following dexamethasone. There was no difference between patients with anorexia nervosa and controls in the rise in plasma cortisol following ACTH. On most measures of HPA activity, the normal weight patients with bulimia were indistinguishable from the controls. These results suggest that HPA activity is normal in most patients of normal body weight with bulimia and that the psychological and behavioral disturbances common to both anorexia nervosa and bulimia are, in the absence of significant weight loss, insufficient to produce major alterations in HPA activity.

Endogenous opioid peptides and the control of the menstrual cycle

This paper reviews recent experimental evidence which supports a role for endogenous opioid peptides in the control of gonadotropin function. In primates, cell bodies containing endogenous opioid peptides have been located within the hypothalamus in areas rich in gonadotropin-releasing hormone (GnRH) and dopamine. The release of beta-endorphin from these hypothalamic neurons is influenced by gonadal steroids, maximal release being observed when both estradiol and progesterone are present. beta-Endorphin has been shown to decrease LH secretion, and naloxone, an opiate antagonist, reverses this action. The LH-releasing activity of naloxone parallels variations in hypothalamic beta-endorphin secretory activity, so that maximal effects are seen during the luteal phase of the cycle. Present evidence indicates that opiates exert their effect on LH via a hypothalamic site. It is concluded that increased opioid inhibition of the GnRH-LH axis is responsible for the decline in LH pulse frequency during the luteal phase. The studies provide evidence for a chemical basis rationalizing relationships between reproductive function and stress, and have further implication on other forms of amenorrhea.

Vasopressin secretion induced by hypoxia in sheep: Developmental changes and relationship to β-endorphin release☆☆☆

To investigate the developmental changes in the secretion of vasopressin and the potential role of beta-endorphin as a stimulus to the release of vasopressin, the concentrations of these peptides were measured in fetal, newborn, and adult sheep after episodes of induced hypoxia. The studies confirm that hypoxia is a potent stimulus to the release of both vasopressin and beta-endorphin in the fetal animal. In both the newborn lamb and the ewe, more profound hypoxia is necessary for a similar release. In the fetus, the release of both vasopressin and beta-endorphin after hypoxia increased with gestational maturation. A comparison of control concentrations of both peptides, the discordance of release in the newborn lamb, and the absence of a change in concentrations of vasopressin with infusion of beta-endorphin implies that these hormones are released in parallel but independently during hypoxic stress.

Hypothalamic-pituitary-gonadal function in Anorexia Nervosa and Bulimia

Patients with anorexia nervosa (AN) exhibit neuroendocrine abnormalities that may result solely from emaciation or may reflect defective endocrine mechanisms which are intrinsic to disordered eating even in the absence of starvation. To distinguish these possibilities, we have studied indices of hypothalamic-pituitary-gonadal (HPG) function in 9 patients with AN, 12 normal weight patients with bulimia and recent or current oligomenorrhea, and 8 normal weight controls. Measurement of 24-hour luteinizing hormone (LH) secretion with 30-min sampling revealed significantly fewer LH secretory spikes and a trend toward lower mean 24-hour LH levels in both bulimic and anorectic patients than in controls. Stimulation with gonadotropin releasing hormone produced elevated LH responses in the bulimic group and blunted LH responses in the anorectic group. Stimulation with estradiol revealed diminished LH augmentative responses and a trend toward diminished follicle stimulating hormone augmentative responses among bulimic as well as AN patients compared to controls. In each instance, the bulimic group tended to show within-group heterogeneity, with some individuals falling within the AN range. These findings suggest that HPG axis abnormalities in eating disordered patients cannot entirely be attributed to emaciation and that factors other than subnormal weight contribute to disturbed hypothalamic-pituitary functioning in these patients.

ACUTE MEIGS' SYNDROME SECONDARY TO OVARIAN STIMULATION WITH HUMAN MENOPAUSAL GONADOTROPINS.

T H E availability of potent gonadotropic preparations of human origin has led to a renewed interest in the use of these substances in the treatment of amenorrhea and infertility. In some instances a marked hyperstimulation of the ovary occasionally leading to serious complications has been observed. The case to be reported here is an example of such massive reaction of the ovaries to the treatment with human menopausal gonadotropin. Because of the serious nature of the complications as well as the rather unique and intriguing chain of physiologic events which ensued, it was felt that a detailed report of the case was warranted.

Precursors of the urinary 11-desoxy-17-ketosteroids of ovarian origin

Abstract A method for determining the level of secretion of ovarian androgens is presented. Application of this method has demonstrated that the ovary secretes dehydroisoandrosterone and Δ 4 -androstenedione and/or testosterone. In patients with hirsutism and abnormal ovarian function, the secretion of the ovarian androgens is increased.