Pituitary responses to synthetic corticotropin-releasing hormone: absence of modulatory effects by estrogen and progestin

To determine if the activity of the adrenocorticotropic hormonal-adrenal axis is modulated in part by estrogens and progestins, we have compared pituitary and adrenal responses to corticotrophin-releasing hormone in normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle and in four women undergoing ovariectomy who received estradiol (E2) implants alone or in combination with oral medroxyprogesterone acetate administration. Basal adrenocorticotropic hormone and cortisol levels (9:00 AM) and responses to ovine CRH were unaffected by variations in E2 and progesterone during each phase of the menstrual cycle. In women undergoing ovariectomy who received E2 replacement therapy, basal concentrations of adrenocorticotropic hormone and cortisol (9:00 AM) and the responses to human corticotrophin-releasing hormone were not altered by administration of E2 alone or E2 with medroxyprogesterone acetate. Under these experimental conditions, our findings suggest that physiologic changes in E2 and progesterone levels during the menstrual cycle and replacement doses of estrogen and progestin commonly used clinically do not significantly influence basal adrenocorticotropic hormone and cortisol levels or responsiveness to corticotrophin-releasing hormone.     

Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized women

Hypothalamic-pituitary-adrenocortical (H-P-A) function was tested in 14 hyperandrogenized women, aged 17 to 32 years, who had been continuously treated with nightly single-dose oral dexamethasone, 0.25 to 1.00 mg, for 3.7 to 16.5 months. Daily AM serum cortisol concentrations were measured in nine subjects after discontinuation of dexamethasone. Basal cortisol concentrations returned to normal (greater than or equal to 6.0 micrograms/dl) within 36 hours in 67%, within 60 hours in 89%, and within 84 hours in 100%. Median time to return to normal was between 12 and 36 hours. Rate of return correlated with both the dose-adjusted duration of dexamethasone therapy (p less than 0.01) and the degree of adrenocortical suppression during treatment (p less than 0.01). The H-P-A response to insulin-induced hypoglycemia and the adrenal response to an acute intravenous adrenocorticotropic hormone (ACTH) challenge were evaluated in eight subjects 12 to 36 hours after the final dexamethasone dose. Thirty-eight percent demonstrated normal cortisol increments to hypoglycemia, 25% had blunted or absent cortisol responses to hypoglycemia but normal cortisol increments to exogenous ACTH, and 38% had blunted or absent responses to both hypoglycemia and exogenous ACTH. The responsiveness of the H-P-A axis correlated with the degree of adrenocortical suppression (p less than 0.05) but not with dose of dexamethasone or duration of treatment. Small doses of dexamethasone are not necessarily "physiologic", but dexamethasone therapy with maintenance of serum cortisol levels greater than or equal to 2.0 micrograms/dl was associated with rapid return to normal basal cortisol concentration and a normal cortisol response to insulin-induced hypoglycemia.     

地塞米松上调禁欲的发情雄性小鼠睾丸间质细胞芳香化酶表达

目的:探讨地塞米松对禁欲的发情雄性小鼠睾丸组织芳香化酶表达的影响。方法:发情昆明雄性小鼠随机分成3组,每组10只:性表达组(A组)、禁欲组(B组)、地塞米松+禁欲组(C组,皮下给地塞米松16.66mg/kg),采用放射免疫法检测各组血清睾酮(T)、雌二醇(E2)水平以及睾丸组织E2含量;采用化学发光法检测血清皮质醇水平;采用原位杂交和免疫组织化学技术检测睾丸组织芳香化酶(P450arom)的表达。结果:C组睾丸间质细胞芳香化酶表达增强(P<0.01),睾丸组织、血清E2水平升高(P<0.01),而血清皮质醇水平降低(P<0.01)。结论:地塞米松可能通过抑制禁欲的发情雄性小鼠肾上腺皮质醇分泌而上调睾丸间质细胞P450arom表达。     

Circadian hormonal interactions among the mother, fetus, and amniotic fluid

Circadian rhythms and hormonal interactions among the maternal, fetal, and amniotic fluid compartments were studied in long-term catheterized rhesus macaque monkeys between days 127 and 138 of gestation (term = 167 days). Blood samples were collected at 3-hour intervals for 48 hours and analyzed by radioimmunoassay for estrone, estradiol, cortisol, progesterone, dehydroepiandrosterone sulfate, and prolactin. Distinct circadian rhythms were present for cortisol and progesterone in the maternal circulation and for progesterone and dehydroepiandrosterone sulfate in the fetal circulation (p less than 0.05). Although maternal and fetal estrogen levels were higher in AM samples than in PM samples, a statistically significant circadian rhythm was not present (p greater than 0.10). Fetal levels of progesterone and dehydroepiandrosterone sulfate and maternal levels of progesterone were highest between 9:00 PM and 3:00 AM and lowest between 9:00 AM and 3:00 PM. Maternal levels of cortisol were highest between 6:00 AM and 9:00 AM and lowest between 6:00 PM and 12 midnight. The circadian patterns of maternal cortisol and progesterone were inversely related to each other (r = -0.68; p less than 0.01). Amniotic fluid cortisol levels were highest between 9:00 AM and 12 noon and lowest between 6:00 PM and 3:00 AM (p less than 0.10). With the possible exception of cortisol, amniotic fluid steroid hormones did not demonstrate distinct diurnal fluctuations, nor did they correlate with steroid changes in maternal or fetal blood. Because the rhesus placenta is permeable to glucocorticoids it is likely that transplacental passage of maternal cortisol influences the activity of the fetal pituitary and adrenal so that the circadian rhythm in the fetal axis is 180 degrees out of phase with that of the maternal axis. The circadian rhythms in fetal dehydroepiandrosterone sulfate and progesterone in late gestation parallel the biorhythm in uterine contraction frequency and amplitude, with peaks during periods of darkness between 9:00 PM and 3:00 AM.     

Direct transport of progesterone from vagina to uterus

OBJECTIVE: To compare progesterone concentrations in serum and endometrial tissue from hysterectomy specimens after vaginal or intramuscular (IM) administration of progesterone gel. METHODS: This was a randomized open study of 14 post-menopausal women undergoing transabdominal hysterectomies. Participants received either vaginal progesterone gel, 90 mg, or IM progesterone, 50 mg, at 8:00 AM and 8:00 PM on the day before surgery and at 6:00 AM on the day of surgery. Venous blood samples for progesterone measurement were collected at 8:00 AM on the day before surgery (baseline) and during surgery. After removal of the uterus, the endometrium was sampled from the anterior and posterior walls. Results were expressed as ratios of endometrial to serum progesterone concentrations x 100. RESULTS: Ratios of endometrial to serum progesterone concentrations were markedly higher in women who received vaginal progesterone (14.1 median, 8.5-59.4 range; 95% confidence interval [CI] 9.89, 38.79) compared with IM injections (1.2 median, 0.5-13.1 range; 95% CI -0.48, 7.39) (P < .005). CONCLUSION: Ratios of endometrial to serum progesterone concentrations were higher after vaginal administration of progesterone than after IM injections. Our findings in endometrial tissue specimens from hysterectomies excluded the possibility of contamination by progesterone that remained in the vagina.     

Adrenal corticoid hyperresponsiveness in hirsute women

Data are limited on the existence of adrenal hyperplasia or cortisol oversecretion in women with hirsutism. Supranormal responses of cortisol (greater than 20 micrograms/dl) were observed at 15 and 30 minutes after the 8:00 A.M. adrenocorticotropin (0.5 U) injection (performed after 1 mg of dexamethasone taken orally at midnight) in 6 of the 12 hirsute women (hirsute I) and in all 4 women with Cushing's disease. Baseline plasma levels of corticoids, androgens, and gonadotropins, body weight, menstrual history, and degree of hirsutism were all indistinguishable between the two hirsute groups. The mean plasma levels of cortisol and 17-hydroxyprogesterone were both significantly greater in the hirsute I group and in those with adrenal hyperplasia caused by Cushing's disease than in normal subjects. Our data indicate that adrenal hyperplasia is a common abnormality in women with hirsutism. We speculate that this abnormality may contribute to the pathogenesis of hirsutism and ovarian dysfunction in many hirsute women.     

Treatment with oral estrone sulphate in the female climacteric. II. Hormonal aspects

Of forty-three perimenopausal women aged 40.1-56.5 years with climacteric complaints 25 were treated with sodium piperazine estrone sulphate 2.5 mg daily and 18 were given methyl scopolamine. All subject had initial serum FSH levels in the postmenopausal range (20 U/l). The serum levels of FSH, LH, unconjugated immunoreactive estrogens, total estrone, total dehydroepiandrosterone (DHAS), and the urinary low polar estrogens were followed during 18 months of treatment. In the estrogen treated group serum unconjugated immunoreactive estrogens and total estrone as well as urinary low polar estrogens increased significantly during treatment. The serum levels of FSH decreased significantly during the whole test period; LH only at three months. No effects could be seen on serum DHAS. In the group given methyl scopolamine the only changes found were a decrease in FSH at three months and a positive trend for LH (during the whole treatment period). In the total material, positive correlations were found between pretreatment values of unconjugated immunoreactive estrogens and total estrone and between total estrone and DHAS. A negative correlation was found between unconjugated immunoreactive estrogens and FSH. It is concluded that the effects of estrogens on the endocrine system in peri- and postmenopausal women are influenced by chemical structure, dosage and mode of administration of the estrogen as well as by the endogenous hormone profile.     

Effect of dexamethasone treatment on sex steroid-binding protein,corticosteroid-binding globulin,and steroid hormones in cycling rhesus macaques

We tested the hypothesis that dexamethasone lowers sex steroid-binding protein levels and observed the effect of dexamethasone on corticosteroid-binding globulin and specific steroid hormones in plasma. Four cycling rhesus macaques were studied during three consecutive menstrual cycles (first and third cycles served as controls). In the second cycle, each animal received 0.5 mg of dexamethasone intramuscularly at 8:00 am and 8:00 pm daily for 21 consecutive days. Blood samples were taken at 1- to 3-day intervals during each cycle. Concentrations of sex steroid-binding protein, corticosteroid-binding globulin, cortisol, testosterone, progesterone, and estradiol were measured in plasma. The percentage and plasma concentration of free testosterone were also determined. Within 2 days of treatment, dexamethasone suppressed cortisol to 5% of baseline values, which returned in the third cycle. All cycles were ovulatory. Dexamethasone significantly lowered plasma levels of all the compounds except progesterone: sex steroid-binding protein, −30%; corticosteroid-binding globulin, −14%; testosterone, −36%; and estradiol, −45%. The percentage of free testosterone was significantly elevated, but free testosterone concentrations were unchanged. Although our data conclusively show that dexamethasone suppresses plasma sex steroid-binding protein levels in the rhesus macaque, it remains to be established whether this suppressive effect leads to an increase in the metabolic clearance rate of testosterone.     

Placental steroid synthesis from DHEAS during dexamethasone therapy.

Maternal glucocorticoid treatment affects estrogen synthesis by decreasing estrogen precursors. Whether glucocorticoid has any effect on the placental conversion of estrogen precursors to estrogen is not known. A study was therefore undertaken to investigate the effect of 100 mg of intravenously administered dehydroepiandrosterone sulfate (DHEAS) on estradiol (E2), estriol (E3), and testosterone (T) serum levels. The test was conducted for 5 hours in 10 women treated with intramuscular dexamethasone and in 8 controls during the last trimester of pregnancy. The initial E2 and E3 serum concentrations were lower in women treated with dexamethasone than in controls, while T serum levels did not display any difference. Following the injection of DHEAS there was a significant increase in E2, with maximal levels reached between 1 and 3 hours after injection in both groups. Maximal levels of E2 were equal for both groups. There was no change in E3 levels after DHEAS administration in the nontreated group, while the increase in the dexamethasone group was significant. A significant rise in T, with maximal levels reached at 1 hour after infusion, was similar in both groups. It is concluded that maternal dexamethasone does not inhibit the conversion of DHEAS either to E2 in the placenta or to E3 and T.     

The Addition of Dexamethasone to Antiandrogen Therapy for Hirsutism Prolongs the Duration of Remission

Objective: To determine whether the addition of dexamethasone to antiandrogen therapy prolongs the duration of remission in women with hirsutism.

Design: Follow-up study of patients treated with one of four regimens: spironolactone (100 mg/d) for 1 year, dexamethasone (0.37 mg/d) for 1 year, dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 1 year, or dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 2 years.

Setting: Academic medical practice in reproductive endocrinology.

Patient(s): Fifty-four women with hirsutism and hyperandrogenism.

Intervention(s): Ferriman-Gallwey-Lorenzo scores were obtained and serum levels of testosterone, unbound testosterone, and dehydroepiandrosterone sulfate were measured before therapy, every 6 months during therapy, and for 1 year after the withdrawal of therapy.

Main Outcome Measure(s): Hirsutism scores and serum indices of hormonal changes were monitored.

Result(s): Ferriman-Gallwey-Lorenzo scores and androgen levels remained low 1 year after the withdrawal of therapy in patients who were treated with dexamethasone, either alone or in combination with spironolactone. In patients who were treated with spironolactone alone, hirsutism scores had returned to baseline values after 1 year.

Conclusion(s): The addition of an agent that suppresses androgen levels may be useful to prolong the duration of remission of hirsutism in women with hyperandrogenism who are treated with antiandrogens.     

The effects of estrogen on adrenal androgens in oophorectomized women

The serum levels of adrenal androgens (aa) are lower in oophorectomized (OO) than in ovulating (OV) women. This study was carried out in an effort to further investigate these findings and to study the effects of administration of estrogen on the levels of aa in OO women. Ten OO and seven OV women participated in this study in which aa were measured basally and after stimulation with adrenocorticotropic hormone (ACTH), both before and 4 weeks after conjugated estrogens (CE). Seven women received 0.625 mg of CE, and five received 2.5 mg of CE. Compared to OV women, OO women had significantly lower levels of androstenedione (Adione), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), testosterone (T), delta 5-androstenediol (Adiol), and 17 beta-estradiol (E2) (p less than 0.01). In response to ACTH, OO women had smaller responses to Adione (p less than 0.05), DHEA (p less than 0.005), DHEA-S (p less than 0.01), 17-OH progesterone (17 Prog) (p less than 0.01), and 17-OH pregnenolone (17 Preg) (p less than 0.1). Furthermore, after ACTH, the ratio of 17 Prog/Adione was significantly higher in OO women (p less than 0.01), thus suggesting reduced 17,20-demolase (17,20D?) activity. Similarly, OO women had higher ratios of 127 Preg/17 Prog (p less than 0.1), DHEA/Adione (p less than 0.01), and Adiol/T (p less than 0.01), thereby suggesting reduced 3 beta ol dehydrogenase-isomerase (3 beta ol) activity. In response to CE, there was a dose-related increase in aa and cortisol. After 2.5 mg of CE, aa were significantly higher and similar to those levels in OV women. despite the known increases in sex hormone binding globulin-finding capacity and transcortin after estrogen, unbound T increased slightly, as did urinary free cortisol in women treated with 2.5 mg of CE. After treatment with estrogen, there was a dose-related change in the ACTH-stimulated steroid ratios that indicated and increase in 17,20D and 2 beta ol activities. In women who were gien 2.5 mg of CE, these enzyme activities were similar to those in OV women.     

多囊卵巢综合征基础血清皮质醇水平及其昼夜规律变化

目的探讨多囊卵巢综合征(PCOS)患者基础血清皮质醇水平及其昼夜规律的变化。方法对2008年7月至2010年5月中山大学附属第一医院生殖医学中心63例PCOS患者(21例肥胖和42例非肥胖)及38名月经正常的健康妇女进行空腹8时(基础)及16时血清皮质醇浓度测定,并比较其昼夜规律消失的比例,同时分析影响基础皮质醇水平的可能相关因素。结果肥胖PCOS组、非肥胖PCOS组及健康对照组的基础皮质醇水平分别为(325.7±125.7)nmol/L,(407.6±165.6)nmol/L和(397.4±129.9)nmol/L。其中肥胖PCOS组基础皮质醇水平明显低于健康对照组(P<0.05)。16与8时皮质醇比值,肥胖(0.78±0.54)及非肥胖PCOS组(0.61±0.34)均较健康对照组(0.46±0.20)显著升高(P<0.05)。肥胖PCOS组皮质醇昼夜规律消失率明显高于健康对照组(47.6%vs.10.5%,P<0.05)。相关分析发现基础皮质醇水平与体重指数呈负相关(P<0.05)。结论 PCOS患者(尤其是肥胖PCOS患者)可能存在下丘脑-垂体-肾上腺轴(HPA轴)的功能紊乱。体重指数对皮质醇的代谢以及HPA轴的激活有重要的影响。     

Effects of tibolone on plasma homocysteine levels in postmenopausal women

OBJECTIVE: To investigate the effects of tibolone on levels of plasma homocysteine, an independent risk factor for cardiovascular disorders, in postmenopausal women. DESIGN: Prospective, randomized clinical study. SETTING: University hospital. PATIENT(S): Postmenopausal healthy women. INTERVENTION(S): Tibolone (2.5 mg/d) or calcium (1250 mg/d) and conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (5 mg/d) were administered orally for 6 months. Blood samples were collected at the start and the end of therapy. MAIN OUTCOME MEASURE(S): Plasma homocysteine levels. RESULT(S): Administration of tibolone and calcium caused only a 4% decrease in plasma homocysteine levels compared with initial levels. In contrast, conjugated equine estrogens plus medroxyprogesterone acetate caused a 29% decrease in plasma homocysteine levels. CONCLUSION(S): Despite the reported beneficial effect of tibolone on the serum lipid profile, tibolone had no statistically significant effect on serum homocysteine levels in postmenopausal women. The possible cardiovascular protective role of tibolone might be unrelated to its effects on homocysteine levels.     

Effect of short- and long-term dexamethasone on 3 alpha-androstanediol glucuronide in hirsute women

The role of glucocorticoid therapy in regulating plasma 3 alpha-androstanediol glucuronide (3 alpha-diol G) content, a marker of androgen action, in hirsute women was unclear. A pulse injection of adrenocorticotropic hormone (0.5 U) following 1 mg of dexamethasone (DEX) at midnight significantly increased the plasma level of cortisol (P less than 0.01), 17-hydroxyprogesterone (17-OHP, P less than 0.01) in 17 hirsute women, but it had an insignificant effect on delta 4-androstenedione (delta 4A), testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 3 alpha-diol G. Human chorionic gonadotropin administered for 3 days produced a significant (P less than 0.01) increase only in 17-OHP. DEX administered as a single dose in the late evening failed to affect the plasma levels of these four androgens when measured at 8:00 A.M. In contrast, when the glucocorticoid was given each evening for over 2 months, plasma delta 4A, DHEA-S, and 3 alpha-diol G were suppressed (P less than 0.001) substantially, as compared with baseline values in 12 hirsute women, 7 with polycystic ovary disease and 5 with idiopathic hirsutism. These observations indicate that chronic glucocorticoid therapy suppresses androgen action in hirsute women.     

Serum naphythylamidase isoenzymes during hormonal treatment. Electrophoretic and quantitative studies.

Alterations in serum naphthylamidase isoenzymes were studied by electrophoretic and quantitative methods in women treated with oral contraceptives and women treated with naturally occurring conjugated estrogens for climacteric symptoms. In women treated with oral contraceptives the appearance of extra isoenzyme components was accompanied by a distinct and significant increase in the total serum naphthylamidase activity, whereas in treatment with conjugated estrogens no such increase was found. The result suggests that combined oral contraceptives and natural estrogens affect the serum naphthylamidase pattern in different ways.     

Correlation of the effects of dexamethasone administration on urinary 17-ketosteroid and serum androgen levels in patients with hirsutism.

Total 24 hour urinary 17-ketosteroid and serum testosterone (T), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and cortisol levels were measured before and during four days of dexamethasone administration in 28 hirsute patients and 10 women with normal ovulatory cycles. Both the base-line urinary 17-ketosteroids and serum androgen levels were significantly higher (p less than 0.05) in hirsute than in normal subjects. Cortisol levels were similar in the two groups. Dexamethasone administration resulted in a significant suppression (p less than 0.05) of all the urinary and serum androgen and cortisol levels in both groups. At the end of suppression the serum DHEA, DS and cortisol levels were similar, while the urinary 17-ketosteroids and serum T and delta levels were still significantly higher (p less than 0.05) in the hirsute than in normal women. There was poor correlation between total urinary 17-ketosteroid and serum androgen results. These finding suggest there is a dual abnormality of androgen production in hirsute patients. The adrenal glands appear to secrete increased quatities of DHEA and DA, while the ovaries appear to produce elevated amounts of T and delta.     

Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women.

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women. Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day), the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day, estradiol 50 micrograms/patch) and the third with transdermal estradiol alone (n = 6) (50 micrograms/day). Before and after 1, 2 and 3 months of therapy, the following circulating steroid and protein hormone levels were evaluated: DHEA, DHEAS, androstenedione, testosterone, estrone, estradiol, 17-hydroxyprogesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta-endorphin, growth hormone (GH) and cortisol, and a Kupperman score was performed. Before and after treatments, plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine, an alpha 2-presynaptic adrenergic agonist (1.25 mg i.v.) (b) naloxone, an opioid receptor antagonist (4 mg i.v.) and (c) fluoxetine, a serotonin selective reuptake inhibitor (30 mg p.o.). In both groups of women treated with DHEAS, mean basal serum DHEA, DHEAS, androstenedione, and testosterone levels significantly increased after treatment, while no changes were shown in the group receiving estradiol alone. Serum estradiol, estrone, GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment, with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG, cortisol, and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine, naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels. After each of the treatments, the beta-endorphin response was completely restored and was similar, independent of the kind of therapy. Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion, which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.     

A study of prolactin, follicle-stimulating hormone, and luteinizing hormone in puerperium: spontaneous variations and the effect of metergoline

In 80 normal puerperae, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), including human chorionic gonadotropin (hCG/LH), and prolactin (PRL) levels were evaluated 6 to 29 hours after vaginal delivery. In these puerperae, PRL levels were higher and FSH levels were lower than in menstruating women; hCG/LH levels were very high, due to persisting hCG levels. The values of the three hormones showed a log-normal distribution, and no relationship was found between the three hormones considered in pairs. Thirty-six puerperae chosen from the above 80 were followed during a 5-day period: 24 were not able to breast-feed their babies and were treated with metergoline, an antiserotoninergic agent able to prevent puerperal lactation, 8 or 12 mg/day; 12 additional puerperae, nursing their babies, were evaluated as controls. In lactating women PRL and FSH levels remained steady during the observation period, while hCG/LH levels progressively decreased. Metergoline lowered PRL levels, when employed at both dosages, and FSH levels only at the higher dosage, without affecting the decline of hCG/LH levels. Since dopaminergic drugs are known to lower serum LH levels and not to affect or to increase FSH levels, our data indicate that metergoline might act through a mechanism of action different from dopaminergic drugs.     

Parameters of lipid metabolism in postmenopausal women on oral or transdermal hormone replacement with or without progesterone

OBJECTIVE: Aim of the study was to show different influences of transdermal and oral hormone replacement therapies (conjugated and micronized estrogens) with or without varying dosages of C21-progestogens on serum lipids and lipoproteins. MATERIAL AND METHODS: We report on serum triglycerides, cholesterol, HDL-, LDL-cholesterol, apolipoprotein A 1 and B levels of 80 postmenopausal women, who received hormone replacement therapies for more than one year. RESULTS: All patients showed increasing (non-significant) serum HDL/LDL-cholesterol-ratios. Transdermal estrogen monotherapy also influenced the lipid parameters in a positive way. Apolipoprotein B, cholesterol and LDL-Cholesterol decreased, apolipoprotein A 1 increased. Transdermal replacement therapy combined with C21-progestagens and all oral therapies resulted in HDL-cholesterol increases. Positive changes in lipid parameters were most remarkably in women receiving oral therapies. The addition of 42 mg medrogestone/cycle caused a more significant decrease of cholesterol serum levels than higher dosages of medrogestone did. During subsequent treatment cycles, serum triglycerides showed increasing levels within the reference limits in women receiving conjugated estrogens and medrogeston. CONCLUSIONS: Transdermal and oral hormone replacement therapies with and without C21-progestogens are ideal for hormone replacement therapy in postmenopausal women with normal or minor pathological lipid parameters. The lowest possible medrogestone dose necessary for endometrium protection should be used.     

Effect of dexamethasone on prolactin secretion in late pregnancy.

It is established that PRL secretion is regulated by estrogens. Glucocorticoids, on the other hand, suppress estrogen secretion during pregnancy and may also inhibit PRL by direct hypothalamopituitary action. In this study PRL and estradiol were determined with specific radioimmunoassays in 14 women during gestational weeks 28 to 34 prior to, during, and following short-term intramuscular dexamethasone administration (12, 8, and 4 mg on three consecutive days) used for prophylaxis of RDS in preterm infants. There were no significant alterations in PRL serum concentrations; estradiol showed a significant drop (P less than 0.001) during all 3 days of treatment, returning to the pretreatment level on posttreatment day 1. The PRL and TSH responses to 200 micrograms of intravenous TRH on day 2 or 3 of dexamethasone treatment in six women during late pregnancy were not inhibited. Short-term dexamethasone treatment with pharmacologic doses does not suppress the physiologic secretion and release of PRL or the release induced by TRH during late pregnancy.