RBC membrane adenosine triphosphatase activities in patients with major affective disorders.

Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.

Short and long term effects of growth hormone on circulating levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1, and insulin: a placebo-controlled study.

The short and long term effects of GH on serum concentrations of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin were investigated in women participating in an in vitro fertilization program. In this placebo-controlled study, sterile saline (eight women) or 24 IU GH (eight women) were given im on alternate days, starting on cycle day 4, in combination with GnRH and human menopausal gonadotropin. IGFBP-1 levels decreased significantly during the first 4 h after GH administration, whereas no significant changes were seen in the placebo group. The concentrations of serum IGF-I and insulin did not change during 4 h after GH injection. During the 11-day follow-up period, serum levels of both IGF-I and insulin were significantly higher in GH-treated than in placebo-treated women. These results suggest that the serum concentration of IGFBP-1 is not completely GH independent. They also support the earlier findings that long term treatment with GH increases serum IGF-I and insulin levels.

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.

Hypoprolactinemia and ovarian function.

Thirty-two patients with ovarian hyperstimulation were randomized to receive bromocriptine or placebo from cycle day 5 onward. Bromocriptine decreased serum and follicular fluid prolactin (PRL), accelerated ovarian follicle growth, increased serum and follicular fluid estradiol, lowered luteal phase progesterone, and shortened the luteal phase length of the cycle. The maximal luteal phase estradiol and progesterone concentrations correlated with each other in the placebo group, but not in the bromocriptine group. These findings indicate that hypoprolactinemia interferes with ovarian function. The unchanged concentrations of gonadotropic hormones and pattern of luteinizing hormone pulsation during bromocriptine suggest direct ovarian effects of hypoprolactinemia. Because PRL suppression enhanced follicular responses and inhibited corpus luteum formation and function, the follicular and corpus luteum actions of PRL may be different.

Response of serum hormones to androgen administration in power athletes.

Endocrine effects of self-administration of high doses of anabolic steroids and testosterone were investigated in five power athletes during 26 wk of training, and for the following 12-16 wk after drug withdrawal. After 26 wk of anabolic steroid and testosterone administration, serum testosterone concentrations had increased 2.3-fold. This was associated with increased concentrations of serum estradiol, which rose 7-fold to values (0.48 nmol X 1(-1) typical for females. There was a major decrease in serum FSH and LH concentrations, but they returned to control levels following drug withdrawal. However, serum testosterone concentrations stayed at low levels (9 nmol X 1(-1) ) during this follow-up period, indicating long-lasting impairment of testicular endocrine function. Serum ACTH concentrations were also decreased during steroid administration, possibly due to a corticoid-like effect of some of the anabolic steroids taken in high doses. However, no changes were seen in serum cortisol. The only consistent change in the control group was an increase in serum LH concentrations during the most intensive training, suggesting that a decreasing tendency of serum testosterone was compensated for by augmented LH secretion.

Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes.

Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of androgenic-anabolic steroids, and during the 13 weeks following drug withdrawal. During the use of steroids significant decreases (P less than 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyroxine, triidothyronine, free thyroxine, and thyroid hormone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P less than 0.001). In relation to the changes in the thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hormone increased at some point of the study 5 to 60-fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P less than 0.001) in serum estradiol. Furthermore, there were major decreases in serum LH (P less than 0.01) and FSH (P less than 0.01) concentrations, and testicular testosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 +/- 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 +/- 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of testicular endocrine function. No consistent changes were found in the eight control athletes.

Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate.

The hormonal and biochemical effects of danazol (600 mg a day) and high-dose medroxyprogesterone acetate (MPA; 100 mg a day) were studied in a placebo-controlled, 6-month trial. Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments, whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA. Both drugs significantly suppressed the sex hormone-binding globulin level (SHBG), and consequently, the free-androgen index (serum total testosterone nmol/l per SHBG nmol/l x 100) as compared with placebo, the effect of danazol being significantly stronger than that of MPA. Danazol, but not MPA, significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and haemoglobin levels, and also thrombocyte counts, whereas MPA, but not danazol, increased the serum concentration of albumin in relation to placebo. Serum total bilirubin, conjugated bilirubin, gamma-glutamyl transferase, creatinine, alkaline phosphatase, sodium and potassium levels and leucocyte counts remained unchanged during both treatments. Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects, while the increase in androgenic activity induced by danazol was greater than that achieved with MPA. Danazol also had more biochemical effects than MPA. It interfered with the functions of the liver and the production of thrombocytes and haemoglobin, whereas MPA affected only albumin synthesis/release.

Static posturography and intravenous alcohol.

Twelve health subjects were assessed using static posturography before and after intravenous alcohol infusion in a double-blind experiment. The dose was 0.5 g ethanol per kg body weight in 15 minutes, which raised the blood alcohol concentration to a level of approximately 1 mg/mL. Among other parameters, the average body sway velocity (BSV) and area of body sway (BSA) were measured. BSV was the most sensitive parameter for detecting increased body sway after alcohol infusion, and a significant effect of alcohol on its values was seen at 0.46 to 1.0 mg/mL alcohol concentrations. The second best indicator was the BSA. There was a positive correlation between the BSV and the BSA. The other parameters were not affected. The Romberg quotient remained constant during the alcohol test. The test battery used was relevant to distinguish the effect of alcohol on balance. In this study, acute blood alcohol concentrations of around 0.5 to 1.0 mg/mL affected BSV more significantly than BSA. The authors do not, however, recommend the test for forensic purposes in examining drivers with alcohol in their blood, as there is too much interindividual dispersion in the results.

Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood.

Early menarche is a risk factor for breast cancer. In a longitudinal manner, we have investigated the endocrine features of girls with early menarche. This study extends our investigations to the third decade of life in a cohort of girls followed up for 13 years. The group studied comprised 44 women, 20-31 years of age. Eleven women had had their menarche before 12.0 years, 14 women at 12.0-12.9 years and 19 women at 13.0 years or more. The women who had had early menarche had higher serum oestradiol concentrations during the follicular phase of the menstrual cycle than the women who had had their menarche later. The serum oestradiol concentrations increased rapidly at the beginning of cycle in these "early menarche" women. If there is a threshold which serum oestradiol concentrations must exceed to increase the risk of breast cancer, then these women have more days at risk than other women. In addition, the serum SHBG (sex-hormone-binding globulin) concentration was about 30% lower in the follicular-phase specimens of the women who had had their menarche before 12.0 years compared with those who had had their menarche at 13.0 years. Our data therefore indicate that women with early menarche are subject to a high degree of oestrogen stimulation at least until approximately 30 years of age. Our findings may have important consequences for the design of intervention programs for breast cancer prevention.

Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne.

Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.

PIP: This study investigated pituitary function in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG), and other biochemical parameters in male acne patients and in female acne patients before and after oral contraceptive (OC) treatment. Among males, basal and stimulated prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were similar among acne cases and controls; however, stimulated LH levels were 60% higher among cases and SHBG levels were 60% higher among cases and SHBG levels were statistically higher. The 33 female acne patients were treated for 6 months with an OC containing 0.03 mg ethinyl estradiol plus 0.15 mg levonorgestrel or 0.15 desogestrel. After 6 months, a 15% and a 30% decrease, respectively, was observed in DHEA-S levels in the 2 groups. Serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, while SHBG elevated 250% in the desogestrel/ethinyl estradiol group and 30% in the levonorgestrel/ethinyl estradiol group. Although acne improved in both groups, the improvement was greatest among cases receiving a desogestrel-containing OC. These findings suggest that low SHBG and elevated DHEA-S are the hormonic alterations most often seen in cases of severe acne, although pretreatment DHEA-S levels did not correlate with the severity of the acne. It is concluded that OCs improve acne by increasing SHBG and decreasing DHEA-S levels.

Maternal serum prolactin and its response to TRH in normal and complicated early pregnancy.

Maternal serum prolactin levels (PRL) were measured by radioimmunoassay in thirty-four women with either normal or complicated early pregnancy. The basal PRL level (mean +/- S.D.) of 33.4 +/- 16.4 ng/ml in normal pregnancy (n = 15) was similar to the level of 32.7 +/- 18.8 ng/ml in threatened abortion (n = 11) and 32.8 +/- 16.9 ng/ml in hyperemesis gravidarum (n = 8). Two patients, one with blighted ovum and the other with subsequent spontaneous abortion, demonstrated PRL levels lower than the range of 20-63 ng/ml in the control group. The PRL response to 200 microgram of synthetic thyrotropin releasing hormone (TRH) administered intravenously was similar throughout the patient groups. The basal level of PRL in the whole series was more closely related to the level of serum oestradiol (r = 0.778, P less than 0.001) than to that of serum progesterone (r = 0.442, P less than 0.05). However the increments of PRL following TRH administration did not correlate with either oestradiol or progesterone.

Induction of ovulation with low-dose estrogen-progestin therapy in amenorrheic patients.

Sixteen amenorrheic patients, five with ovarian and 11 with hypothalamic failure, were treated for three cycles with a biphasic low-dose estrogen-progestin regimen consisting for esterified estrogen, 1.5 mg/day for 21 days, combined for the last 7 days with norethisterone acetate, 5 mg/day. Serum FSH and LH decreased significantly (P less than 0.01) during treatment in the ovarian failure group, and FSH in the hypothalamic failure group. Estradiol levels increased on average two-fold during treatment and decreased again after treatment, these changes being slower in the hypothalamic than in the ovarian failure group. Withdrawal bleeding occurred in all patients during the treatment cycles. After treatment, six patients with hypothalamic failure had spontaneous menstrual bleedings. Judged by serum progesterone measurements, one ovulation occurred in each group during the treatment cycles, and in the hypothalamic failure group, two ovulations were observed 3 wk after treatment. Four women with secondary amenorrhea are presented, in whom conception occurred during biphasic estrogen-progestin treatment; three of these cases had hypergonadotrophic ovarian failure. Our results suggest that low-dose estrogen-progestin treatment may induce ovulation in selected cases of hypothalamic and also of ovarian failure.

Haematological values for the Finnish reindeer.

Red blood cell counts, haemoglobin, packed cell volumes and total and differential leucocyte counts as well as E-MCHC, E-MCH, E-MCV values and the osmotic fragility of erythrocytes are described for the Finnish reindeer. The samples were taken in early autumn from 52 reindeer of varying ages.

Effects of experimental hyperprolactinemia and clomiphene on pituitary responsiveness to LHRH and TRH in men.

The effect of clomiphene citrate during sulpiride-induced hyperprolactinemia on pituitary function was tested in 8 healthy men, who ingested 100 mg of clomiphene, 150 mg of sulpiride or 100 mg of clomiphene + 150 mg of sulpiride daily for 7 days. Clomiphene treatment increased FSH and LH plasma concentrations and this increase was unaffected by sulpiride-induced hyperprolactinemia. Sulpiride intake alone did not alter serum gonadotropin concentrations. A reduced LH response to LHRH during sulpiride intake was seen, whereas the FSH response was unchanged. The prolactin response to TRH was unaffected during the combined sulpiride + clomiphene ingestion. Sulpiride treatment did not change the basal and/or clomiphene-stimulated gonadotropin secretion in healthy men. Thus, oligozoospermic men using psychotropic drugs and/or with hyperprolactinemia may be suitable candidates for clomiphene treatment.

Intra-amniotic or intravenous injection of dehydroepiandrosterone sulphate: simultaneous changes in steroid levels in amniotic fluid and maternal serum.

Levels of unconjugated oestradiol-17 beta (E2) and testosterone (T) and total oestriol (E3) were measured hourly to 6 h after intra-amniotic (i.a.) (100--200 mg) or intravenous (i.v.) (100 mg) injection of dehydroepiandrosterone sulphate (DHEA-S) in a series of twenty-six women with mid-trimester abortion. Amniotic fluid E2 and T levels were elevated significantly 1--6 h after the i.a. injection of DHEA-S, while the E3 level in amniotic fluid did not change. The i.a. administration also induced significant rises in serum E2 and T levels between 1 and 6 h and in the serum E3 level between 2--6 h. The i.v. injection of DHEA-S was accompanied by significantly elevated serum levels of E2 and T, while the E3 concentration remained unchanged. It appears that following maternal i.v. administration or an amniotic fluid injection, DHEA-S is rapidly converted to E2 and T, and these accumulate in both the maternal circulation and the amniotic fluid. E3, however, is formed only after i.a. administration of DHEA-S, and is selectively transported to the maternal blood.

Adrenocortical function of patients using oral contraceptives.

PIP: To investigate the possible changes in adrenocortical function during the use of different oral contraceptives, 43 women of fertile age were studied. 35 were using orgal contraceptives of the estrogen-gestagen type, the estrogen-gestagen sequential type, or the low-gestagen type. 8 women were controls. Each member of the test groups had been taking contraceptive pills for at least 2 menstrual cycles. Adrenocortical function was measured by assaying photofluorimetrically the 11-OHCS content of the plasma during the synthetic adrenocortioctrophic hormone (ACTH) (Homactid) test. The dose of the hormone used was 10 mcg given im. Plasma samples were obtained before and 15, 30, 60, and 120 minutes after injection. Tests were done on Days 15-20 of the menstrual cycles. The plasma 11-OCHS level in the low-gestagen group was the same as in controls both before and during the test. The combined type contraceptives had an elevating effect on the 11-OHCS level in the plasma; these levels both before and during the ACTH test ranged from nearly significant to p less than .01 with some of the readings reaching significance at the p less than .001. The difference is assumed to be due to an increased transcorting content of the plasma and to the increased biological half-life of cortisol induced by estrogen. This could also explain why the metabolic change noted in association with estrogen-gestagen oral contraceptives is similar to that seen in corticosteroid-induced diabetes. Similar readings were found for the patients taking the sequential contraceptives, with values ranging from nearly significant at 0-15 minutes to highly significant (p less than .001) from 30 to 120 minutes.^ieng