Origin of serum estradiol in postmenopausal women.

In postmenopausal women, the circulating levels of estrone (E1) and estradiol (E2) may be of clinical importance. The origin of E1, but not of E2, has been defined. To examine the source of the latter, the serum concentrations, metabolic clearance rates, conversion ratios, and production rates of testosterone (T), androstenedione (A), E2, and E1 were measured in 20 postmenopausal subjects. For E2, the mean +/- SE CRTE2 was 0.0014 +/- 0.0005; thus, the contribution of circulating T to the circulating E2 pool was minimal (2.5%). The contribution of circulating A to E2 was also insignificant, whereas the CRE1E2 was appreciable (0.065 +/- 0.011), accounting for 21.5% of the E2 pool. For E1, the major contribution was the peripheral conversion of A, accounting for 24.6% of circulating E1. The contribution of peripheral conversion of T (unmeasurable) and E2 (2.9%) to the E1 pool were minimal. These data are consistent with the concept that in postmenopausal women the major contribution of peripheral conversion to the circulating E2 pool is from E1, which in turn is the product of peripheral aromatization of circulating A.

Biological effects of various doses of conjugated equine estrogens in postmenopausal women.

To determine which dosage of estrogen might provide physiological replacement and also avoid possible harmful side effects, 21 postmenopausal women were studied before and after the oral administration of conjugated equine estrogens. The dosages studied were 0.15, 0.30, 0.625, and 1.25 mg/day, with each being given for 6 weeks. Fifteen premenopausal women were also studied, and their values were presumed to reflect normal physiological function. Variable responses of the different biochemical and biological markers of the action of estrogen were observed. Both LH and FSH levels showed stepwise decreases with increasing amounts of estrogen, but even 1.25 mg/day did not suppress these hormones to the range found in premenopausal women, suggesting a subphysiological response. The lower dosages of conjugated estrogen had minimal effects on vaginal cytology, with only the 1.25-mg dose changing the maturation index to values similar to those found in premenopausal subjects. The 0.3-mg dose of conjugated estrogen was the lowest amount that resulted in a significant reduction (P < 0.05) of the urinary calcium to creatinine ratio (an index of bone resorption). Liver protein synthesis was the most sensitive parameter to the action of estrogen. Hepatic resoponses were variable depending on which protein was assessed. These data indicate that the oral administration of conjugated equine estrogens results in inconsistent effects. All doses exerted subphysiological, physiological, and pharmacological responses at the different sites of action.

Ovarian and adrenal steroidogenesis in a virilized patient with gonadotropin-resistant ovaries and hilus cell hyperplasia.

A 26-year-old woman with secondary amenorrhea, temporal balding, and clitoromegaly was found to have both the gonadotropin-resistant ovary syndrome and hilus cell hyperplasia. Simultaneous sampling of peripheral and ovarian venous blood revealed excess ovarian testosterone secretion to be the probable cause of the patient's virilism. The marked response of the ovary to stimulation by luteinizing hormone (LH) coupled with the lack of ovarian follicular development suggested that an isolated resistance of the ovarian follicle to follicle-stimulating hormone (FSH) was present in this patient. The administration of a daily pharmacologic dose of dexamethasone for 14 days was followed by the patient's first menstrual period in 13 years, raising the possibility that autoimmunity may have been involved in this patient's ovarian resistance to FSH stimulation.

Effects of human serum on transport of testosterone and estradiol into rat brain.

The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]-dihydrotestosterone (DHT), and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique, In the absence of plasma proteins, approximately 90% of plasma T, DHT, or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in seven different clinical conditions: pregnancy, oral contraceptive use, thin and obese postmenopausal, follicular phase female, hirsutism, and normal male; the level (mean +/- SD) of sex hormone-binding globulin (SHBG) varied from 17 +/- 5 nM (hirsutism) to 323 +/- 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT, or E2 transported into brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of testosterone (r = 0.99) and estradiol (r = 0.98) was observed. These studies indicate that a) the undirectional clearance by brain of both testosterone and estradiol is inversely related to the SHBG level and b) the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma testosterone or estradiol.

Serum androgens and estrogens in postmenopausal women with and without endometrial cancer.

Thirty-five consecutive patients with adenocarcinoma of the endometrium and an equal number of control subjects matched to the cancer patients for age and percentage of ideal weight were studied prospectively. In the cancer patients, the mean +/- SE serum androstenedione, testosterone, estrone (E1) and estradiol (E2) levels were 503 +/- 34 pg/ml, 224 +/- 22 pg/ml, 38.7 +/- 3.6 pg/ml, and 14.5 +/- 0.9 pg/ml, respectively. Similar concentrations were found in the control subjects. Body weight and percentage of ideal weight showed highly significant correlations (P less than 0.001) with E1 and E2 but not with the androgen concentrations in either group. The heavier patients had higher E1 and E2 levels. Age and years since menopause did not correlate with any of the hormonal levels. The cancer patients with overt diabetes tended to be more obese and have higher estrogen levels than did the nondiabetic subjects. Those with a history of prior estrogen usage were more slender and had lower endogenous estrogens than the nonusers. Twenty-three of the cancer patients (66%) had a presumed risk factor(s) for the development of this tumor, that is, excess body weight, high endogenous estrogen levels, or a history of prior estrogen usage. These data support the concept that conditions which lead to continued, unopposed estrogen stimulation may be associated with malignant transformation of the endometrium.

Age-related changes of calcitonin secretion in females.

Calcitonin secretion was studied in 50 normal females from 20--69 yr of age, with 10 subjects in each decade. Hormone measurements were made by RIA during response to a 10-min infusion of calcium (as the chloride salt) at 3 mg/kg BW. There was a progressive decrease of the calcium-stimulated plasma calcitonin with age. Linear regression analysis demonstrated a significant (P less than 0.05) negative correlation (r = 0.29) between calcitonin response and age. Postmenopausal females had a significantly (P less than 0.01) smaller calcitonin response than premenopausal females. The time of maximum calcitonin response progressively shifted from 10 min in the younger subjects to 20 min in the older subjects. These studies demonstrated that calcitonin secretion decreases with age in females. This decrease may play some role in the pathogenesis of the progressive loss of bone mass which occurs with aging in females.

Relationship of fasting urinary calcium to circulating estrogen and body weight in postmenopausal women.

Circulating estradiol (E2), estrone (E1), adrostenedione, and testosterone levels were measured in 40 normal postmenopausal women of widely varying body weights. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Significant positive correlations of E2 and E1 were found with body weight and correlations of E2 and E1 were found with body weight and percent ideal weight but not with height, age, or years since menopause. No correlations were observed between circulating androstenedione and testosterone levels and any of these characteristics. Significant negative correlations were noted between Ca:Cr and percent ideal weight and between Ca:Cr and E2 and E1 concentrations. Administration of 10 micrograms ethinyl E2 to 10 postmenopausal subjects for 30 days reduced Ca:Cr to the level observed in 20 premenopausal women. These data suggest that body weight can influence urinary calcium excretion. It is possible that the reduced amounts of endogenous estrogen found in conjunction with low body weight may be a factor contributing to the greater loss of urinary calcium and the more frequent occurrence of osteoporosis in slender postmenopausal women.

Circulating levels of pregnancy specific beta 1 glycoprotein in late pregnancy: nyctohemeral and day-to-day variation, and variation during labour.

Circulating levels of pregnancy-specific beta 1 glycoprotein have been determined in a number of physiological situations in late pregnancy. The apparent variation in five subjects studied over a 24-hour period was not in excess of that due to the assay. Excess variation was apparent in 2 of 11 subjects studied daily for up to 8 days, and in 6 of 16 patients studied serially during labour.

Elevations in skin temperature of the finger as an objective index of postmenopausal hot flashes: standardization of the technique.

The present study was designed to validate and standardize a technique of continuous recording of skin temperature of the finger as an objective index of hot flashes. Significant skin temperature rises (greater than 1 degree C) were recorded in close temporal relationship to 69% of subjective hot flashes experienced by seven postmenopausal women. The temperature elevations occurred at an interval of 54 +/- 10 minutes (mean +/- standard error) and lasted an average of 31 minutes. The mean increase was 2.7 degrees +/- 0.2 degrees C. The extent of the temperature elevations found in the postmenopausal subjects was significantly greater than in premenopausal control subjects (P less than 0.05) and was reduced by estrogen treatment (P less than 0.02). This study substantiates that the recording of skin temperature changes of the finger provides an objective index of hot flashes. This should assist in the investigation of the underlying disturbance and provide more accurate evaluation of modes of therapy.

Hypercarotenemia in hypothalamic amenorrhea.

Six patients are described with hypothalamic amenorrhea and associated hypercarotenemia. The commencement of the hypothalamic amenorrhea followed weight reduction or stress in each case. The subjects were otherwise healthy and had none of the associated stigmata of anorexia nervosa. None of the subjects had ingested excessive quantities of vegetables or fruits rich in carotene. Although all six patients had elevated serum carotene levels, only three had clinically apparent yellow pigmentation of the skin. The exact mechanism responsible for hypercarotenemia in patients with hypothalamic amenorrhea is not apparent. Mobilization of lipid stores and catabolic changes occurring with weight-loss states appear to be related in some undefined way to the elevated carotene levels.

LH, FSH and skin temperaure during the menopausal hot flash.

Six postmenopausal women, who were experiencing frequent hot flashes, had an 8 h continuous recording of skin temperature over the dorsum of the finger as an objective index of hot flashes. Frequent blood samples were obtained during the time of the recording for the measurement of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. During the 48 h of recording 34 significant temperature elevations were recorded and 32 were associated with a subjective hot flash. 3l pulses of LH release were also observed with 26 occurring simultaneously with the temperature rises. Correlation analysis of simultaneous skin temperature and circulating LH levels showed a significant positive correlation (p less than 0.01). FSH levels showed no consistent relationship with skin temperature. These data suggest that LH or the factors that trigger its pulsatile release are related to the mechanism responsible for the initiation of hot flashes.

A retrospective study of induction of labour.

The labour, delivery and state of the newborn were compared retrospectively in a group of women who had labour induced and a group who started labour spontaneously. There were 200 women at term in each group, individually matched for age, parity and social class and with no medical or obstetric complications prior to labour. The induced group showed a higher incidence of epidural anaesthesia, fetal monitoring and operative delivery. Sixty had forceps deliveries and five had Caesarean sections compared with two forceps deliveries and no Caesarean sections in the 'spontaneous onset' group. The higher incidence of operative deliveries in the induced group was not fully explained by the excess of epidurals and fetal monitoring received. More of the babies born after an induced labour had endotracheal intubation during resuscitation.