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Biomedical subjects

D R Meldrum

Publications and source records attributed to D R Meldrum.

At least 181 records · Page 10Linked to original sources
PubMed1983

Induction of hot flashes in premenopausal women treated with a long-acting GnRH agonist.

To examine the relationship between the occurrence of menopausal hot flashes and the pulsatile release of LH, we have investigated the serum hormone levels and the occurrence of hot flashes by objective recordings in five women with endometriosis given daily injections of a long-acting GnRH agonist (GnRH-a) for 28 days. Results were compared to the findings made in 25 young women 6-8 weeks after bilateral oophorectomy. Serum levels of estrone and estradiol were similar in the subjects given GnRH-a and the women who underwent a surgical castration. In comparison with values before GnRH-a administration, the mean FSH level was lower whereas the mean LH concentration was significantly higher (P less than 0.01) on the last day of therapy. The coefficients of variations of both gonadotropins measured during 4-h sampling periods at 20-min intervals before and at the end of GnRH-a administration were significantly reduced (P less than 0.01) with therapy. During the total of 20 h of frequent sampling in the 5 subjects, 15 pulses (20% rise from nadir) of LH and 12 pulses of FSH were detected before GnRH-a, whereas only 2 and 8 pulses, respectively, were observed on day 28 of treatment. Hot flashes were observed in both groups of patients. The proportion of women experiencing hot flashes, the rate of occurrence/h and the characteristics of the physiological changes were similar in the 2 groups of women. These data indicate that hot flashes can occur in the absence of prominent LH pulses, suggesting the pulsatile release of this hormone is merely associated with the hot flash rather than being etiological.

Castration↗
PubMed1983

Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist.

The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

Adrenal Cortex Hormones↗
PubMed1983

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

To determine whether vaginal administration of conjugated equine estrogens (VCE) could provide physiological replacement while avoiding effects on hepatic function, as occurs with oral administration, a study was conducted in which 20 postmenopausal women were evaluated before and after the vaginal administration of CE. The dosages studied were 0.3, 0.625, 1.25, and 2.5 mg/day for 4 weeks. Twenty premenopausal women were also studied, and their values were presumed to reflect normal physiological function. The findings in the postmenopausal women were compared with previously reported results obtained in a similar group of subjects given oral CE (OCE). Vaginal cytology returned to premenopausal values with 0.3 mg VCE. This response was similar to that exerted with 1.25 mg OCE. Stepwise increases in circulating estrone and estradiol occurred with increasing dosages. The 2.5-mg dosage of VCE raised estrone levels to values similar to those in premenopausal women in the late follicular phase, and estradiol concentrations were similar to early follicular phase concentrations. Limited or no responses of the systemic markers of estrogen action occurred with all doses of VCE. Small decreases in LH and FSH levels occurred, but no dosage significantly reduced the level of either gonadotropin. Although the urinary calcium to creatinine ratio was significantly reduced by the two largest dosages of VCE, the effect of the 2.5-mg dosage was less than that observed with 0.625 mg OCE, the lowest dosage that protects against osteoporosis. Hepatic protein synthesis was significantly increased only by the higher dosages tested. No dosage had a significant effect on circulating levels of triglycerides or total or fractionated cholesterol levels. These data suggest that the vaginal administration of CE exerts mainly a local effect, with limited or no measurable changes in systemic markers of the action of estrogen.

Administration, Oral↗
PubMed1983

Estrogen replacement therapy: indications and complications.

Estrogen replacement therapy is one of the most controversial issues in the field of reproductive medicine. Indications for its use include hot flashes, vaginal atrophy, and risk of osteoporosis. Risk of heart disease may also be an indication but this use has not been firmly established. The role of estrogen replacement therapy in aging changes of skin needs clarification. Complications of therapy include endometrial cancer, breast cancer, hypertension, hyperlipidemia, and gallbladder disease. The last three complications presumably result from hepatic actions of estrogen replacement therapy.

Animals↗
PubMed1983

Hormonal effects of danazol and medical oophorectomy in endometriosis.

The hormonal effects of danazol and of a long-acting gonadotropin-releasing hormone analogue (GnRH-a) were studied in women with endometriosis and those with oophorectomy. During danazol treatment, total serum concentrations of estrone and estradiol, and free, dialyzable estradiol were reduced to the low follicular phase range for premenopausal women. Corresponding estrogen levels were suppressed to a significantly greater degree (P less than .02) at the end of GnRH-a administration, to concentrations which were twofold to fourfold lower than with danazol therapy and similar to values in the oophorectomized women. Sex hormone binding globulin was markedly suppressed (P less than .001) throughout danazol treatment, resulting in a threefold elevation (P less than .01) of free testosterone. These data suggest that danazol may affect endometriosis by mechanisms other than by inducing a pseudomenopause. The increased tissue availability of testosterone may be responsible for acne and hirsutism observed in some women during danazol treatment and may inhibit proliferation of the ectopic endometrium. Medical oophorectomy using GnRH-a may have improved effects on endometriosis without the androgenic side effects of danazol.

Castration↗
PubMed1982

"Medical oophorectomy" using a long-acting GNRH agonist--a possible new approach to the treatment of endometriosis.

Five women with endometriosis were given a daily dose of a potent long-acting GnRH agonist, D-Trp6-Pro9-Net-LHRH (GnRH-A) for 28 days in an attempt to suppress ovarian estrogen secretion. The mean level of estradiol (E2) during sampling over 24 hours decreased (P less than 0.01) from 62 +/- 11 to 10 +/- 1 pg/ml at the end of treatment. Mean concentrations of androstenedione, testosterone, estrone and E2 on day 28 of therapy were similar to those measured in oophorectomized women. The level of FSH was decreased (P less than 0.001) during GnRH-a, whereas that of LH was significantly (P less than 0.001) increased, suggesting differing intracellular control mechanisms for release of the two gonadotropins. Desensitization of the pituitary was demonstrated at the end of treatment by a complete lack of acute response of FSH or LH to the daily dose of GnRH-a. "Medical oophorectomy" provides a new approach to the treatment of endometriosis.

Endometriosis↗
PubMed1982

Estrogen levels in postmenopausal women with hot flashes.

Following menopause, some women are troubled by hot flashes (episodes of flushing and perspiration), whereas others do not experience the symptom. To determine whether the extent of estrogen deficiency influences the occurrence of the disturbance, the authors measured the levels of estradiol (E2), estrone (E1), and sex-hormone binding globulin (SHBG), and the percent and total non-SHBG-bound E2 in 24 women with frequent hot flashes and 24 women who had never experienced the symptom. Significantly lower levels of E2 (P less than .002), E1 (P less than .05), percent non-SHBG E2 (P less than .05), and total non-SHBG-bound E2 (P less than .01) were found in the symptomatic women. Similar differences were confirmed in 18 subject pairs matched for age, years since menopause, and presence or absence of ovaries. The finding of a significantly (P less than .05) lower percent ideal body weight in the women with hot flashes suggests that the known effects of body weight on the rate of extraglandular estrogen production and the level of SHBG in postmenopausal women may be important variables determining the occurrence of hot flashes.

Age Factors↗
PubMed1982

Effect of clonidine on hot flashes in postmenopausal women.

The effectiveness of clonidine in suppressing the occurrence of postmenopausal hot flashes was examined using a dose-response study design and objective recordings of hot flashes. Patients with frequent flashes were studied before and after oral administration of placebo and 0.1, 0.2, and 0.4 mg of clonidine daily for 2 weeks at each dose level. Finger temperature and skin resistance were recorded as indices of hot flash episodes. Four of 10 subjects beginning the study withdrew because of drug-related side effects. Clonidine was found to reduce significantly the frequency of hot flashes as compared with baseline (P less than .005) and with effects of the placebo (P less than .05). At the maximum dosage the mean rate of hot flash occurrence decreased 46%. It was concluded that clonidine does reduce the frequency of postmenopausal flashes.

Body Temperature↗
PubMed1981

Association of waking episodes with menopausal hot flushes.

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest the menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy.

Age Factors↗
PubMed1981

Effect of megestrol acetate on flushing and bone metabolism in post-menopausal women.

To avoid the risks of oestrogen therapy in post-menopausal women, we have examined the effects of a progestin, megestrol acetate (MA), on hot flushes and bone metabolism. Ten normal post-menopausal women were studied before and after the oral administration of 20, 40 and 80 mg of MA daily for 4 wk at each dose level. Finger temperature and skin resistance were recorded for 8 h as objective indices of flushing and perspiration, respectively. The fasting ratios of urinary calcium: creatinine (Ca/Cr) and hydroxyproline: creatinine (OHPr/Cr) were used as indices of bone resorption. A reduction (P less than 0.01) of flushing episodes was noted on all dose levels of MA, with 56, 11, 6 and 1 flushes occurring on 0, 20, 40 and 80 mg of medication. A decrease (P less than 0.05) of Ca/Cr was noted only with 80 mg of MA, whereas OHPr/Cr remained unchanged. We conclude that progestin therapy may provide an alternative mode of treatment for post-menopausal hot flushes. Definitive demonstration of an effect on post-menopausal bone resorption will require a long-term study of bone density.

Bone and Bones↗
PubMed1981

Objectively recorded hot flushes in patients with pituitary insufficiency.

A study was conducted of 2 young adult women with pituitary insufficiency and complaints of hot flushes. Both underwent continuous recordings of skin temperature of the finger and skin resistance over the sternum as objective indices of flushing episodes. Frequent blood samples were also obtained during the recordings for the measurement of serum LH and FSH levels. During the 10 h of recording, 12 subjective hot flushes occurred and each was associated with a rise of finger temperature of greater than 1 C. Eighty-five percent of the temperature rises were associated with measurable decreases in skin resistance. The mean interval between flushes, the magnitude of the skin temperature and resistance changes, and the relationship of these changes to the onset of subjective flushes were identical to those observed in symptomatic postmenopausal women. Circulating gonadotropin levels were in the low to low normal range in comparison to values observed in premenopausal women and showed minimal pulsatile release. There were no significant correlations between finger temperature changes and LH levels in either subject. These results suggest that the previously described association of pulsatile LH release and the occurrence of hot flushes in postmenopausal women cannot be attributed to augmented LH secretion per se and, therefore, may be due to hypothalamic factors responsible for pulsatile LH release.

Adult↗
PubMed1981

Microsurgical tubal reanastomosis--the role of splints.

Tubal reanastomosis was performed in 32 patients using microsurgical techniques. In 25 women, occlusion was due to prior sterilization. A splint was not used during or after repair. Intrauterine pregnancy occurred in 21 (84%) and fetal loss in 6% of 17 potentially viable pregnancies. The mean midluteal serum progesterone level of previously sterilized patients (13.4 +/- 1.0 ng/ml) was similar to the level in normal partners of infertile men (12.9 +/- 1.5 ng/ml) and in women with other tubal causes of infertility (14.3 +/- 1.1. ng/ml). Seven patients with occlusion due to disease achieved postoperative patency; there were 4 (57%) intrauterine pregnancies and 1 tubal gestation. The author concludes that a splint is not necessary in performing tubal reanastomosis and that there is no clinical or laboratory evidence of luteal insufficiency in this group of previously sterilized women.

Fallopian Tubes↗
PubMed1981

Changes in circulating steroids with aging in postmenopausal women.

to examine the possible effects of aging on circulating steroid hormones in postmenopausal women, blood samples were drawn from 155 women, aged 34 to 83 years, with spontaneous ovarian failure. The C-21 steroids, pregnenolone and 17-hydroxypregnenolone; the delta 4 progestins, progesterone and 17-hydroxyprogesterone; and cortisol did not change with age and were similar in concentration to the levels measured during the follicular phase of premenopausal women. The delta 5 androgens, dehydropiandrosterone and dehydroepiandrosterone sulfate, declined significantly (P less than .001) with age, whereas no change was noted in the delta 4 androgens, androstenedione and testosterone. The levels of estradiol (E2) and estrone (E1) were strongly correlated with percent ideal weight but did not change with age. The authors conclude that 1) The production of progestins does not change with age in normal adult women, other than that resulting from the loss of secretion associated with ovarian corpus luteum function. 2) The decline of delta 5 androgens without corresponding changes in their precursors suggests an age-related change of adrenal 17,20 desmolase activity. 3) The levels of E2 and E1 reflect an effect of body size but not of age on peripheral aromatization of precursor androgens.

17-Hydroxycorticosteroids↗
PubMed1981

Objective techniques for the assessment of postmenopausal hot flashes.

The present study was undertaken to evaluate objective methods of monitoring postmenopausal hot flashes. Continuous recordings of finger and core temperature and sternal skin conductance were carried out in 8 postmenopausal and 4 premenopausal women. Four postmenopausal patients were studied a second time following 30 days of daily oral administration of ethinyl estradiol 0.05 mg. One hundred twenty flashes were subjectively noted and recorded during 104 hours of study in the postmenopausal women. Eighty-two, 98, and 81% of subjective flashes were associated with changes in finger temperature, skin conductance, and core temperature, respectively. The rate of occurrence and magnitude of changes of physiologic markers were significantly greater (P less than .01) in postmenopausal than premenopausal women. Estrogen replacement therapy not only eliminated the subjective sensations but also significantly reduced (P less than .02) the frequency and magnitude of the changes in physiologic function measured by finger temperature. Measurement of skin conductance changes was the single most sensitive and specific indicator of hot flashes. The simultaneous change of both skin conductance and finger temperature, although less sensitive, was a very specific indicator of a hot flash. These results support the concept that the measurement of physiologic changes can be used to assess objectively the occurrence of this symptom complex.

Adult↗
PubMed1980

Postmenopausal hot flushes: a disorder of thermoregulation.

The changes in cutaneous and body temperature and cutaneous conductance during hot flushes in eight postmenopausal women were studied. The vasomotor changes occurred approx. 45 sec after the patients experienced the initial subjective symptoms of the attacks. The rise in skin conductance appeared to be a more reliable index of the flushing episode than did the change in skin temperature. On the basis of the changes recorded it is suggested that the hot flush syndrome may represent a specific thermoregulatory disorder rather than being due to a non-specific central autonomic discharge. The episodes may be triggered by a neuroendocrine imbalance following the disruption of ovarian function and fall in estrogen production. In assessing the frequency and severity of hot flushes, and the effects of treatment, objective measurements of skin and core temperature and skin conductance should replace subjective criteria.

Adult↗