A group-comparative study of effects of Ovestin cream versus premarin cream in post-menopausal women with vaginal atrophy

Fourteen post-menopausal women with vaginal atrophy applied, intravaginally, Ovestin® cream (0.5 mg oestradiol/day; 7 patients) or Premarin® cream (1.25 mg conjugated oestrogens/day; 7 patients) for 3 wk. Effects on plasma E₁, E₂, E3, FSH, LH, PRL, TRH-stimulated PRL release, SHBG, and on maturation value (MV), ferning (F) and spinnbarkeit (S) were studied. Endometrial biopsies at pre-treatment and at 2 wk were obtained from 2 patients from each group.

Premarin induced a significant and progressive rise in E₁ and E₂ levels and in SHBG, whereas Ovestin induced no changes. Both creams increased E₃ slightly and suppressed FSH and LH, Premarin suppression of FSH and LH being significantly greater. No significant changes in PRL or TRH-stimulated PRL release occurred with either cream. A similar, marked rise in the MV occurred, but the effect of Premarin on F and S was significantly greater. Endometrium remained atrophic in the 2 Ovestin-treated patients, but moderate proliferation occurred in the 2 Premarin-treated patients. The data showed Ovestin cream to be superior to Premarin cream because of the absence of undesirable effects on E₁ and E₂ levels and the subsequent changes in SHBG and endometrium.     

Pituitary-thyroid function and thyrotropin, prolactin and growth hormone responses to TRH in patients with chronic alcoholism

Basal plasma concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), free T4 index (TF4I), free T3 index (FT3I) reverse T3, 3,3',5-triiodothyronine (rT3), resin T3 uptake (TR3U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T3 and rT3 plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT3U levels, while those without cirrhosis had increased RT3U and normal TBG levels. Plasma concentrations of basal as well as TRH-stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T3 levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease.     

Serum levels of oestrogens, progesterone, follicle-stimulating hormone and sex-hormone-binding globulin during simultaneous vaginal administration of 17β-oestradiol and progesterone in the pre- and post-menopause

Serum concentrations of 17β-oestradiol (E₂), unconjugated oestrone (E₁), total oestrone (tE₁), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 μg micronized E₂ and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5–8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8–10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10–15 h after administration. Significantly higher absorption of E₂ and E₁ (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women.

In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a ‘pre-menopausal’ pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E₂ and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.     

Biological and endocrine aspects of transdermal 17β-oestradiol administration in post-menopausal women

The plasma protein distribution of oestradiol (E₂) and oestrone (E₁) during transdermal E₂ administration (100 μg/24 hr) was studied in 12 post-menopausal women. The E₂ and E₁ levels observed were 43–83 pg/ml and 37–73 pg/ml, respectively. The levels of the free, albumin-bound and sex-hormone-binding globulin (SHBG) bound fractions were in the ranges 1.4–1.9%, 60–65% and 35–45%, respectively, in the case of E₂, and 2.8–3.0%, 80–89% and 15–20%, respectively, in that of E₁. The SHBG levels also remained unaltered. It was concluded that transdermal administration of E₂ at the dosage employed produces a physiological plasma protein distribution of E₂ and E₁ and does not affect liver protein production.     

Antagonism of oestrogen-induced prolactin release by medroxyprogesterone acetate

Previous studies conducted at our clinic suggested that the administration of hormone replacement therapy (HRT) in postmenopausal women could result in the inhibition of oestrogen-induced prolactin (PRL) release. The aim of this study was to determine how the pituitary function is affected by the sequential addition of medroxyprogesterone acetate (MPA) to oestrogen replacement therapy. Twenty-one postmenopausal women receiving no other medication were treated with a standard dose (0.625 mg/day) of conjugated equine oestrogens (CEE) for a period of 24 days, plus 5 mg/day MPA added sequentially during the last 12 days of the oestrogen therapy. Blood samples were collected before treatment, during oestrogen and oestrogen-progestogen administration and after cessation of treatment. Folliclestimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E₂) and PRL levels were studied. During treatment gonadotrophin concentrations decreased significantly, while after cessation of HRT the levels of FSH and LH increased. These gonadotrophin fluctuations indicated a sharp rise in E₂ levels during therapy and a significant decrease during the treatment-free period. PRL levels were found to be higher during CEE therapy, but they fell when patients received CEE in combination with MPA. These observations suggest that the role of progestogens in a variety of experimental and clinically relevant situations needs to be investigated not only as regards their direct action but also their modulation of the effect of oestrogen.     

Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in post-menopausal women

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE₁S, 2.5 mg/day) and oestradiol valerate (E₂V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 μg/day) were compared in 8 post-menopausal women, using a randomized cross-over design.

The end points measured in peripheral plasma included oestrone (E₁), oestradiol (E₂), oestriol (E₃), oestrone sulphate (E₁S), oestradiol sulphate (E₂S) and oestriol sulphate (E₃S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed.

The plasma levels of E₃ were invariably below the detection limit (220 pmol/1). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E₃S following PE₁S administration than those recorded after E₂V ingestion.

The terminal half-lives of the circulating oestrogens measured after PE₁S administration did not differ from those found after E₂V administration.

After 21 days of PE₁S administration (in combination with LNG for the the last 10 days), the maximum levels of all the oestrogens (except those of E₂) were significantly higher than those seen after the first dose. No such difference was observed after E₂V administration.

There was no difference between the effects of the two treatment regimens with regard to the E₁/ E₂ ratios, but the E₁/E₁S ratios were significantly lower after PE₁S treatment than after E₂V administration.

It is concluded that, compared with an equivalent dose of PE₁S, daily repeated oral administration of E₂V yields consistently lower peripheral plasma levels of E₂ and its principal metabolites. However, in contrast to PE₁S therapy, prolonged administration of E₂V does not result in an accumulation of the circulating oestrogens measured.     

The treatment of postmenopausal vaginal atrophy with Ovestin vaginal cream or suppositories: clinical, endocrinological and safety aspects

Seventy-four postmenopausal women presenting with vaginal atrophy were treated with either Ovestin® vaginal cream (Group A, 23 women: 1 mg/day E₃; Group B, 30 women: 0.5 mg/day E₃) or vaginal suppositories (Group C, 21 women: 0.5 mg/day E₃), applied daily for 3 wk (A and B) or 2 wk (C) before retiring. Ten women from A and 10 from B applied a maintenance dose (1 application twice weekly) during wk 4–16. Effects on vaginal cytology, cervical mucus and clinical and colposcopic findings were studied. Endometrial biopsies were done in 16 patients (A) before and after 3 wk of treatment, and, in 8 of the cases, at 16 wk. A routine laboratory screening program was performed before and after 16 wk of treatment in 10 patients (A). Plasma samples for hormone level determinations were obtained in 32 patients.

Clinical and colposcopic findings showed a beneficial effect of treatments, confirmed by vaginal smears, and persisting during maintenance therapy. Effect on cervical mucus was slight to moderate. No side effects occurred and tolerance was very good. Endometrium remained atrophic under treatment. Screening program revealed no abnormalities. Treatments induced a sharp rise in plasma E₃, followed by a gradual decline. Gonadotropins were slightly suppressed. E₁, E₂, PRL and SHBG capacity remained unchanged.     

三叶因子3在大鼠腺垂体嗜色细胞中的定位

目的探讨三叶因子3(TFF3)在腺垂体远侧部嗜酸性细胞和嗜碱性细胞中的表达,明确TFF3在远侧部的分布。方法采用相邻切片的免疫组织化学染色,在相邻切片上分别显示TFF3/生长激素(GH)、TFF3/催乳素(PRL)、TFF3/促甲状腺激素(TSH)、TFF3/促肾上腺皮质激素(ACTH)、TFF3/卵泡刺激素(FSH)、TFF3/黄体生成素(LH)的表达。结果 TFF3和各嗜色细胞的免疫反应产物为棕黄色,主要位于细胞质,ACTH免疫阳性信号在胞膜也有表达,主要分布在腺垂体的远侧部。邻片显示TFF3存在于部分GH、PRL、TSH、ACTH、FSH、LH细胞,分别占19.4%、22.4%、9.2%、6.5%、35.7%、8.3%,以FSH最多,PRL、GH次之。结论垂体远侧部TFF3可分别表达于GH、PRL、TSH、ACTH、FSH、LH细胞。     

What role of estrogens in ovarian stimulation

Estrogens and progesterone represent the key ovarian hormones produced by the developing ovulatory follicle. Serum concentrations start to rise from the mid-follicular phase onwards, coinciding with the development of the dominant follicle. Androgens are converted into estrogens by aromatase activity of the granulosa cells and secreted into the follicular fluid compartment. Their significance for oocyte maturation and fertilizing potential remains unknown.

Paradoxically, serum estrogen levels are within the normal range in the majority of patients presenting with cycle abnormalities due to ovarian dysfunction. Similarly, the distribution of estradiol (E₂) and follicle-stimulating hormone (FSH) levels within the normal range is comparable between normo-ovulatory controls and normogonadotropic anovulatory women. Moreover, E₂ levels are only moderately correlated with luteïnizing hormone (LH), testosterone (T), androstenedione (A), sex hormone binding globulin (SHBG), the free androgen index (FAI) and finally ovarian volume as measured by ultrasound. No correlations could be found between E₂ and age, body weight and cycle history and FSH. Androgen concentrations and cycle history – but not E₂ – were the most prominent predictors of ovarian response tot the conventional ovulation induction.

Anti-estrogenic compounds like clomiphene citrate and tamoxifen have remained the first-line treatment of choice for anovulation. Certainly, CC and to a lesser extent tamoxifen have demonstrated to exhibit undesired anti-estrogenic properties at the uterine level however. However, large follow-up studies demonstrate cumulative ovulation rates around 75%, and the overall pregnancy rates of around 50%.

Aromatase inhibitors, another way to interfere with estrogen feedback, represent a feasible option. This claim should, however, be substantiated by further sufficiently powered, controlled studies, and the possibility of embryo toxicity remains a major concern.

In retrospect, CC and tamoxifen represent the first generation of selective estrogen receptor modulators (SERMs), and many new compounds have recently been introduced into the clinic or are currently under investigation. The major focuses of these compounds are bone density, the cardiovascular system and breast cancer. No studies have been reported in the area of ovarian stimulation.     

Hormone levels in healthy post-menopausal women and in women with post-menopausal bleeding with or without endometrial carcinoma

FSH, oestrone (E₁), 17β-oestradiol (E₂) and androstenedione (A) were determined in 250 healthy pre- and post-menopausal women, with ages ranging from 40 to 78 yr. These hormone levels were not found to have changed significantly in women of this stable, post-menopausal phase after the age of 54. The results found in this group of women (n = 107), who now range between the ages of 55 and 78, were compared with results from two groups of women who were found to have gynaecological disorders. The first group consisted of 45 women with post-menopausal bleeding without endometrial carcinoma. The second group consisted of 38 women with post-menopausal bleeding and endometrial carcinoma.

FSH was determined by double-antibody radioimmunoassay. E_l, E₂ and A were fractionated chromatographically after extraction with ether and determined radioimmunologically. The data were analysed using the Kruskal—Wallis test and the Wilcoxon test.

When comparing the measurement of hormone levels in the healthy group of women with that of women with post-menopausal bleeding without endometrial carcinoma, no differences were found. However, in the group of women with post-menopausal bleeding and endometrial carcinoma, lower levels of FSH and E₂ and increases in the E₁/E₂ ratio were found; both changes were statistically significant. The slight increase in E₁ and A found in these women was not significant. Any changes which occur in the hormone levels of women with endometrial carcinoma may indicate a correlation between hormones and the onset of endometrial carcinoma.     

The effect of estrogen treatment on plasma concentrations of steroid hormones, gonadotropins, prolactin and sex hormone-binding globulin in post-menopausal women

Twenty-one post-menopausal women on no other medication were treated with a low dose (0.625 mg/day) of conjugated equine estrogen (CEE) for a mean (+/- SEM) period of 2.6 +/- 0.2 mth (range 1.75-4.75). Blood samples were collected before and at the completion of therapy, and alterations in the levels of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG) and certain steroid hormones, including the free testosterone (T) index (T/SHBG) were studied. Following treatment, a significant increase in SHBG levels produced a significant decrease in the free T index (P less than 0.005). As expected, no changes were observed in the levels of PRL and steroid hormones other than estrone (E1) and estradiol-17-beta (E2). Our observations indicate that treatment of post-menopausal women with low-dose estrogen lowers the unbound T.     

Hormone-active intradural spinal metastasis of a prolactinoma — A case report

Summary A 44-year-old woman developed acute severe visual field defects and was operated on a macroprolactinoma. Since complete resection of the tumor was not possible, radiotherapy was performed and in addition to hormone replacement therapy, bromocriptine (up to 60 mg daily) was started without however complete normalization of PRL levels. Four years later PRL levels increased to 10⁵ µU/ml despite continuation of dopamin agonist (mesulergin) treatment. As shown by ophthalmological examination and computer tomography there were no signs of regrowth of the pituitary tumor. At that time the patient complained of severe lumbar pain and myelography revealed a tumor mass in the spinal cord (L₁–L₂). Since the spinal tumor was not removable, laminectomy was performed. Histology and immunohistochemistry demonstrated a metastasis of the prolactinoma. Radiotherapy and bromocriptine in extreme doses (140 mg daily) together with an antiestrogen were not able to improve the neurological deficits (paraparesis) and to lower the PRL levels. This case of a metastasis of a prolactinoma after operation, radiotherapy, and dopamin agonist treatment stresses the importance of close surveillance of patients with prolactinomas without PRL normalization during dopamin agonist therapy and shows for the first time the possibility of ectopic PRL production due to an intradural spinal metastasis.Abbreviations ACTH adrenocorticotropin - FSH folliclestimulating hormone - GH growth hormone - Gy Gray - L lumbar - LH luteinizing hormone - µU/ml microunits per milliliter - mU/ml milliunits per milliliter - PRL prolactin - TBG thyroxine-binding globulin - TSH thyrotropin - T₄ thyroxine - T₃ triiodothyronine     

Endometrium and plasma hormone profile in the peri-menopause and post-menopause

Endometrial histology and plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E₂), oestrone (E₁) and progesterone (P) were studied in 483 women over a period of 13 yr (6 yr before and 7 yr after the start of definitive amenorrhoea, defined as the last menstrual bleeding). The patterns for these parameters were established on the basis of the results of 1227 gonadotrophin and steroid determinations and 721 endometrial biopsies.

Three periods were identified. During the first, from year −6 to year−3, gonadotrophin levels increased gradually, while those of E₂ remained normal, with peaks in some cases. Mean plasma P levels were within the normal range until year −3, but they then decreased progressively. Endometrial histology was similar to that observed during reproductive life.

In the second period, from year −3 to year +1, there was a concomitant rise in gonadotrophins as the E₂ and P levels decreased. However, at the start of definitive amenorrhoea, the mean E₂ and P levels fluctuated between 60 and 100 pg/ml and between 2 and 3 ng/ml, respectively. The endometrium reflected this decrease in E₂ and P production. It was not atrophic but proliferative when definitive amenorrhoea commenced.

During the last period, from year +1 to year +7, gonadotrophins reached a plateau at high levels, while those of E₂ continued to fall, reaching very low values at year +4, after which they reached a plateau. P levels were at the detection limit of the technique.

The correlations between all plasma steroid levels and endometrial histology demonstrated discrepancies in 30% of cases: prliferative or hyperplastic endometria were seen at E₂ levels of under 60 mg/ml, atrophic endometric at E₂ levels of over 60 pg/ml and secretory endometria at very low P levels.     

Pituitary hormonal profile in menopause

The hormonal profile of pituitary hormones was studied by measuring serum FSH, LH, TSH, prolactin (PRL) and growth hormone (GH) in a series of postmenopausal women 50–85 yr old who were at least 1 yr postmenopausal.

In 116 women mean (±SD) plasma FSH and LH were 55.8 ± 22 mU/ml and 25.6 ± 13.62. In 27 women, 1–5 yr after the menopause (M), mean FSH was 56 ± 23.8 and LH 24.7 ± 11 mU/ml and in 22 women, 6–9 yr after M, FSH was 60.3 ± 24.6 mU/ml and LH 27.9 ± 17.2 mU/ml. There was then a gradual, but not statistically significant (n.s.) fall of FSH and LH to 51.6 ± 22.6 and 23.9 ± 9 in 23 women, 20 or more years after M.

TSH was measured in 75 women and its mean value was 4.3 ± 2.4 μU/ml. Three hypothyroid values (70, 20 and 13.5 μU/ml) were also found. Mean TSH value in 20 women aged 50–54 yr (4 ± 2.7 μU/ml) was not significant compared to other age-groups or to 8 women aged 70–85 yr (4.57 ± 2.5 μU/ml).

Mean PRL in 62 cases was 0.54 ± 0.20 mU/ml. In 17 other women unexplained increased values (>1 mU/ml) of PRL were found. No significant change of PRL was found with advancing age.

Mean GH in 32 women was 3.7 ± 2.6 ng/ml. Eight other values were found <1 ng/ml and 3 above 10 ng/ml. The distribution of values in the age-group 50–59 yr (n = 22) did not differ from the age-group 60–85 yr (n = 21).

It is concluded that the basal concentration of gonadotrophins, after an initial rise, as well as that of the other pituitary hormones remains practically unaltered with advancing age in postmenopausal women.     

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women

Objectives: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma β-endorphin (β-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n=6). Methods: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an 2 presinaptic agonist for adrenergic system, (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E₁) and estradiol (E₂) levels were evaluated before and after treatment, while plasma β-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. Results: Basal plasma β-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E₁ and E₂ significantly increased after treatment. The clonidine test induced a significant increase of plasma β-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GH levels increased both before and after treatment. Conclusions: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary β-EP to clonidine, an 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary β-EP secretion.     

Effects of intravaginal oestrogen treatment upon the vaginal absorption of conjugated equine oestrogens

Conjugated equine oestrogens (0.625 mg) were administered daily and intravaginally to 7 post-menopausal women (aged 70–93 yr) for 14 days. Blood samples were taken at days 1 and 14 immediately before and 2, 4 and 6 h after oestrogen application and at days 4, 6, 8, 11 and 13, 4 h after application. Serum samples were analyzed with respect to total oestrone (E₁), unconjugated 17β-oestradiol (E₂), FSH and LH. Serum total E₁ and E₂ increased rapidly at day 1 to luteal and follicular phase levels respectively. After that total E₁ levels decreased to a plateau corresponding to follicular phase values and remained at that level throughout the treatment period. Serum E₂ remained at the follicular phase level during the entire period of treatment. No increase in serum oestrogens could be detected after oestrogen application at day 14. Serum gonadotrophins were already suppressed at day 4 and further decreased to premenopausal values during the latter half of the treatment period. It is speculated that the effects of oestrogens upon a post-menopausal vaginal mucosa involves a diminished resorption of conjugated oestrogens. This effect is, however, not sufficient to avoid systemic effects at the dosage used.     

The TSH secretion in the human pituitary adenomas

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.     

Changes in somatotropin and thyrotropin secretory patterns in aging rats

In order to clarify whether pituitary enlargement influences the secretory patterns of growth hormone (GH) and thyrotropin (TSH) in old rats, we studied the correlation between pituitary weight and plasma levels of GH and TSH in Sprague-Dawley rats of different age and sex. Young female (3–4 months; YF), old female (25 months; OF), and senescent female (33–35 months; SF) rats and young male (3–4 months; YM) and old male (24–26 months; OM) rats carrying chronic intraatrial cannulas were used. Sequential blood samples were removed through the cannulas while the animals remained conscious and undisturbed. Plasma TSH and GH as well as serum thyroxine (T₄) and triiodothyronine (T₃) were measured by radioimmunoassay. At two years of age, both males and females showed a consistent decline in GH pulse amplitude without change in trough levels. By 33–35 months of age, females showed a reversal in the previous pattern of change for GH secretion: pulse amplitude, trough levels, and mean plasma GH increased significantly with respect to the old females. The correlation between mean plasma GH and anterior pituitary (AP) weight was positive and significant (p<0.01) for females but nonsignificant for males. Old and senescent rats showed significantly lower serum T₄, but not T₃, than young animals while plasma TSH increased with age in both sexes. The present results show for the first time that senescent females hypersecrete GH and suggest that the age-related alteration of TSH secretion in rats may be due to the low levels of T₄ present in the aged animals. The correlation analysis shows that pituitary enlargement is in general associated with increased secretion of both GH and TSH in senescent female rats.     

Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women

Objective: We investigated the long-term effects of oral estriol (E₃) on serum levels of total cholesterol (t-Cho), high-density lipoprotein cholesterol (HDL-Cho), low-density lipoprotein cholesterol (LDL-Cho), and triglycerides in early menopausal women. Methods: We studied 67 healthy early menopausal women who were treated for 48 months with 2.0 mg of E₃ plus 2.5 mg of medroxyprogesterone acetate daily (E₃ group, n=21), 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily (CE group, n=19), or 1.0 μg of 1-hydroxyvitamin D₃ daily or 1.8 g of calcium lactate containing 250 mg of elemental calcium daily (control group, n=27). The serum levels of t-Cho, HDL-Cho, LDL-Cho, and triglycerides were evaluated at baseline and every 6 months. Results: After 48 months of treatment, the t-Cho decreased significantly by 4.3±2.1% (mean±SE) from baseline in the E₃ group, did not change in the CE group (−1.9±2.1%), and significantly increased (5.4±3.4%) in the control group. The HDL-Cho significantly increased in the CE group (10.7±2.4%), but not in the E₃ group (3.8±3.3%) or in the control group (−3.6±3.0%). The LDL-Cho significantly decreased in the CE group (−11.4±4.0%), did not change in the E₃ group (−5.2±3.6%), and significantly increased in the control group (11.8±6.3%). The triglyceride level decreased significantly in the E₃ group (−6.7±4.9%), whereas it significantly increased in the CE group (17.6±11.4%), and did not change in the control group (6.1±6.4%). Conclusions: Oral E₃ prevented a postmenopausal rise in the t-Cho. Oral estriol did not induce the hypertriglyceridemia that was seen after treatment with conjugated estrogen. Oral E₃ may be a useful alternative therapy in women with hypertriglyceridemia and in women who are reluctant to continue conventional hormone replacement therapy because of uterine bleeding.     

Comparative metabolic study of percutaneous versus oral micronized 17β-oestradiol in replacement therapy

The aim of this study was to compare the metabolic effects of two presentations of 17β-oestradiol (E₂) which are of recognized effectiveness in the prevention of post-menopausal bone loss, one being administered via the oral and the other via the percutaneous route. During this prospective, randomized study, 32 patients were treated for 2 mth with either 2 mg/day of oral micronized E₂ (n = 16) or 3–5 mg/day of percutaneous E₂ (n = 16). Both regimens proved efficacious, since significant increases in oestrone (E₁) and E₂ concentrations ranging up to mid-follicular values were observed.

In the percutaneous-treatment group we noted a significant decrease in triglycerides (TG), without any significant changes in high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). In the oral-treatment group, we saw no significant increase in HDL-C, although significant increases were observed in body weight, TG, plasma renin substrate (PRS) and sexhormone-binding globulin (SHBG) as well as significant decreases in antithrombin III (AT III) activity and antigen. All of these metabolic variations led us to the conclusion that oral E₂ at the dose established as effective in preventing post-menopausal osteoporosis may, even when micronized, alter certain metabolic and haemostatic parameters in a population characterized by increases in cardiovascular risk factors and morbidity. Oral oestrogen replacement therapy should therefore continue to be used only in carefully selected patients and be strictly followed up by systematic checks on a series of metabolic criteria.