Inge Dyrenfurth

Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes.

Thermoregulatory, cardiovascular and endocrine changes were simultaneously monitored in 11 post-menopausal women with frequent hot flashes (catecholamine and LH levels were measured in 5 and 6 subjects respectively). Plasma samples were obtained at 1- and 5-min intervals. Hot flashes were accompanied by abrupt increases in plasma epinephrine (about 150%) and concomitant decreases in norepinephrine (about 40%). Increased luteinizing hormone was associated with most hot flashes. A detailed sequence of hot flash-associated changes was established. An aura preceded the onset of the hot flash by several seconds. HR and FBF increased just before the onset of the flash and reached peak levels of 10-20 beats/min and 30-fold respectively. Coincident with vasodilation and sweating, finger temperature increased an average of 3.9 degrees C and esophageal temperature fell 0.2-0.6 degrees C. Flashes of both discrete and prolonged intervals were observed. Sensation was a reliable index of flash occurrence and intensity as measured physiologically. Our observations are consistent with the hypothesis that hot flashes are due to a change in the thermoregulatory set point. Furthermore, the changes in catecholamine levels are consistent with the cardiovascular changes accompanying hot flashes.

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.

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.

Ovarian hyperstimulation syndrome: Report of a case with notes on pathogenesis and treatment☆

Abstract A case of ovarian hyperstimulation is described. This syndrome infrequently appears as a complication of induction of ovulation with human menopausal and chorionic gonadotropins. The clinical manifestations are weight gain, extreme ovarian enlargement, ascites with pleural effusion, oliguria, and hypotension. Severe cases may become life-threatening due to marked fluid shifts, electrolyte imbalance, intravascular hypovolemia, and hypercoagulability. The pathogenesis of this syndrome is discussed, and suggestions are made about management. Therapy is symptomatic, expectant, and conservative unless surgical intervention becomes necessary in cases of intraperitoneal bleeding due to ovarian rupture. Physicians using gonadotropins for the treatment of infertility should be thoroughly familiar with the physiopathology of this complication.

Section of the pituitary stalk in the rhesus monkey. I. Endocrine studies.

The effects of pituitary stalk section on anterior pituitary secretion were studied in 20 female rhesus monkeys. Vascular connections between the hypothalamus and the pituitary gland were permanently interrupted in all but 4 animals. Prolactin levels rose rapidly and remained significantly elevated in all effectively stalk-sectioned animals for as long as the observation period (up to 3 years). Only smaller and transient elevations of prolactin were seen in the animals in which revascularization of the anterior pituitary gland had occurred. Growth hormone and cortisol were significantly decreased after stalk section, and were not released by insulin. Radioimmunoassayable luteinizing hormone (LH) levels decreased following surgery and, by bioassay, LH became undetectable within 5 weeks after stalk section, indicating that gonadotropin-releasing hormone is essential for the viability of the gonadotrope. The results indicate that plasma prolactin concentrations can be used to monitor completeness of pituitary gland isolation from direct hypothalamic influence. Stalk-sectioned monkeys provide good models to study direct pituitary effects of various hormones or drugs.

Pulsatile administration of gonadotropin-releasing hormone for induction of ovulation

Chronic pulsatile administration of gonadotropin-releasing hormone (GnRH) was used to induce ovulation in 12 women with various ovulatory disorders. In the first group of eight patients with normal to low baseline levels of gonadotropin, seven responded favorably to the treatment. Follicular maturation was observed in 57% of the treated cycles, and normal ovulatory cycles were induced in 24% of the patients. Two patients became pregnant. The intravenous route of administration was more effective than the subcutaneous one, possibly in response to the GnRH profile after each pulse. (The amplitude of GnRH peaks after an intravenous pulse was four times that seen after a subcutaneous one.) In contrast, follicular maturation and ovulation could not be induced in four women of a second group of patients with normal baseline levels of follicle-stimulating hormone but with high and frequent pulses of luteinizing hormone. The conclusion reached was that pulsatile administration of GnRH can be a new therapeutic tool in the treatment of ovulatory disorders in women who have an insufficient endogenous release of GnRH.

Intravenous infusion of prostaglandin F2α in the mid-luteal phase of the normal human menstrual cycle

The luteolytic effect of PGF2alpha was studied in 3 normal women. Plasma levels of estrogens progesterone and gonadotropins were measured daily. Following a control cycle an infusion of 100 mcg/minute of PGF2alpha over an 8 hour period was given. 2 subjects received the PGF2alpha on the 9th and one on the 5th postovulatory day. The steroid patterns during the control and treatment cycles were not significantly different and the length of the luteal phases was identical. To accentuate luteal activity 2 subjects received in subsequent cycles 10000 i.u. HCG 48 hours prior to the PGF2alpha infusion. In these cycles despite the PGF2alpha the steroids continued to rise and then gradually declined in a normal fashion. The luteal phase was not curtailed. All subjects experienced nausea vomiting painful uterine contractions staining and temperature elevations above 100 degrees Fahrenheit during infusion. It is concluded that in the human PGF2alpha at the given dose was not luteolytic. (authors)

Luteomas of pregnancy: A cause for maternal virilization☆

Abstract A case of marked maternal virilization, developed in the last trimester of pregnancy, is reported. During cesarean section, large luteinized cystic ovaries were found, and one ovary was removed. Histology revealed thecomatosis with extensive luteinization and multiple cystic follicles. Markedly increased levels of testosterone and Δ 4 -androstenedione were found in plasma and follicular fluid, while dehydroepiandrosterone was normal. Urinary 17-ketosteroids, 17-ketogenic steroids, androsterone, and etiocholanolone were elevated as well. In spite of the high levels of androgens which caused maternal virilization, the female neonate was not virilized. A second pregnancy was uneventful without any signs of virilization. Since this lesion is benign and regresses after pregnancy, treatment should be conservative.

The Use of Human Menopausal and Chorionic Gonadotropins for Induction of Ovulation: Sixteen Yearsʼ Experience at the Sloane Hospital for Women

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.