Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol

The maturation value (MV), cervical mucus paråmeters (ferning, Spinnbarkeit), oestrone (E₁), oestradiol (E₂), oestriol (E₃), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), growth hormone (GH), sex hormone binding globulin (SHBG), cortico-steroid binding globulin (CBG) and thyroxin-binding globulin (TBG) were determined in 11 post-menopausal women presenting with vaginal atrophy prior to, and following, treatment with Ovestin® vaginal cream containing 0.5 mg/day of E₃ for 8 wk. In 6 of the patients E₃ was measured during frequent plasma sampling on days 1, 21 and 56; in the same patients and on the same days TRH-stimulated PRL, TSH and GH levels were estimated.

While the therapy induced a sharp rise in the MV, there was a moderate effect on ferning/Spinnbarkeit. Baseline E₃ rose from undetectable levels to a mean value of 86.8 pmol/1 at day 21. E₃ levels achieved during frequent plasma sampling were higher on day 1 than on days 21 and 56 - a decline of the areas under the response curves being significant (P₂-sided = 0.03). There was a slight supression of FSH and LH. No changes in the circulating levels of E₁, E₂, SHBG, CBG, TBG, PRL, TSH and GH were seen. TRH-stimulated PRL, TSH and GH levels remained unaffected. Clinical effect was excellent and no untoward effects were reported.     

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.     

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.     

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.     

少弱精子、无精子症患者生殖激素及染色体检测结果分析

目的探讨男性少弱精子、无精子与血清生殖激素及染色体核型的关系。方法对少弱精子、无精子症患者进行染色体以及血清生殖激素检测,并对结果进行比较分析。结果染色体异常总数占60例,异常发生率达33.33%。性染色体异常53例,占异常总数的88.33%,常染色体异常7例,占异常总数11.67%。无精子症组卵泡刺激素（FSH）、黄体生成素（LH）、垂体催乳素（PRL）均显著高于正常精液组（P〈0.01）,且FSH升高幅度均大于LH,睾酮（T）呈显著性降低（P〈0.05）,雌二醇（E2）无显著性变化（P〉0.05）;与正常精液组比较,少精子症组FSH、LH均高于正常精液组（P〈0.01）,T均呈降低趋势（P〈0.01）,E2、PRL均无显著性变化（P〉0.05）。结论男性不育少弱精子、无精子症患者常规做染色体检查和性激素检测是必要的,对确定其是否有治疗价值及是否应用内分泌治疗提供重要依据。     

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.     

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.     

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.     

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.     

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.     

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.     

Comparative endocrinological and clinical effects of percutaneous estradiol and oral conjugated estrogens as replacement therapy in menopausal women

Sixty-three healthy post-menopausal women participated in the study aimed at determining the efficiency of percutaneous administration of estradiol (E₂) giving physiological plasma levels of the estrogen to provide an efficient relief of climacteric and urogenital symptoms. Among these women, 31 had previous hysterectomy and were randomly allocated to one of the two estrogen replacement therapies while, similarly, the 32 women having an uterus were randomly divided between two groups who received in addition to estrogens, micronized oral progesterone. As estrogen, women received either E₂ by percutaneous administration (Oestrogel) or oral conjugated estrogens (Premarin). With Oestrogel, serum E₂ and estrone levels were within those seen during premenopause and showed a ratio close to 1.0. Climacteric symptoms were reduced or eliminated similarly in all groups. No change was noticed on the concentration of serum angiotensinogen with Oestrogel therapy while a 2.5-fold increase was found in women receiving Premarin. As indicated by the 24-week endometrial biopsy, the progestational response induced by oral progesterone at the dose used was sufficient in twenty out of thirty-two women to cause endometrial atrophy, thus suggesting the need for higher amounts of micronized progesterone in a proportion of women. The present data also indicate that Oestrogel provides efficient relief of climacteric and urogenital symptoms without exerting any detectable effect on hepatic function while maintaining the ratio of serum E₂/E₁ at the physiological value of 1.0.     

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.     

Effects of vaginally-administered oestriol on post-menopausal urogenital disorders: a cytohormonal study

Forty post-menopausal women with urogenital disorders who were inpatients in the same geriatric hospital were treated with oestriol (E₃) for 6 weeks. For the first 2 weeks 0.5 mg E₃ (Leo AB, Sweden) was administered intravaginally every day. Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose. Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index (KPI), while the degree of maturation of the vaginal epithelium was estimated visually. Urinary bacteria were cultivated. A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E₃ treatment. However, neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E₃, since the KPI returned to pretreatment values within 4 weeks. The effect of E₃ administration on the vaginal epithelium was overestimated by the visual assessment method. No changes were seen in urinary bacteria. Medroxyprogesterone acetate was given before and after E₃ treatment. None of the women suffered from withdrawal bleeding.     

Developmental, Neuro and Immunotoxic Effects of Perinatal Diazepam Treatment in Rats

In utero exposure of rats to low dosages of diazepam (1.0—2.0 mg/kg) has been found to result in depression of the cellular and humoral immune responses during adulthood. Behavioral dyshnctions were also reported in infants from mothers with high benzodiazepine (BDZ) intake during pregnancy. The present experiment was undertaken to reconsider the potential action of diazepam during ontogeny in order to obtain hrther information about developmental processes using a refined methodology. Time-pregnant rats were treated subcutaneously with diazepam (2.0 mg/kg/day: group E₁) or with diazepam vehicle (group C) from gestational day 14 to 20. Other dams (group E₂) received the same BDZ dose from the 1^st to the 21^st day of lactation (weaning) or were not treated, remaining undisturbed in their home cages (group C₂). The following results were obtained for animals perinatally treated with diazepam compared to groups C1 and C₂: 1- increased time for testis descent and decreased time for vaginal opening (group E₂); 2- no changes in the dates for ear end eye opening, or incisor tooth eruption (groups E₁ and E₂); 3- increased locomotor activity in the open-field (group E₂) and/or in the plus maze (groups E₁ and E₂); 4- decreased levels of anxiety measured in the plus maze (goups E₁ and E₂); 5- decreased macrophage spreading and phagocytosis (groups E₁ and E₂). These results, which occurred in the absence of overt signs of maternal or fetal toxicity, demonstrate developmental, neuro- and immunotoxic effects of perinatal diazepam treatment in rats.     

An oestrone-releasing vaginal ring in the treatment of climacteric women

Post-menopausal patients were treated with a new form of oestrogen administration by using two types of oestrone-containing vaginal rings. It was observed that oestrone was absorbed from the vagina as demonstrated by elevated plasma concentrations of oestrone (E₁) and oestradiol (E₂). In 3 out of 4 patients the ratio of E₁/E₂ was 4–5 in the first plasma samples collected after the initiation of the treatment. After the first week of treatment this ratio had dropped to 0.8–1.5, which indicates an increase and stabilization in the conversion of oestrone to oestradiol within 1 wk of treatment.

The high levels of plasma oestrogens were associated with a decrease of plasma gonadotrophins and the disappearance of climacteric symptoms. The first type of ring tested resulted in a high initial burst of oestrone release, as evidenced by high concentrations of oestrone and oestradiol during the first 2 wk.

In the second type of vaginal ring the high initial oestrone release was not present and the plasma oestrone and oestradiol levels were stable. The patients tolerated the treatment well, and after gaining experience, easily accepted this route of self-administration. It seems that the vaginal silastic ring is an effective steroid-delivery system in post-menopausal women. As judged by plasma oestrone and oestradiol profiles, it seems that the second type of ring was preferable to the first one as an intravaginal releasing device.     

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.     

Acute dopaminergic blockade augments the naloxone-induced LH rise in estrogen-treated postmenopausal women

Objectives: To assess the effect of estrogen replacement on the simultaneous blockade of the dopaminergic (DA) and opioidergic neural control of hypothalamic-gonadotropic function in postmenopausal women. Methods: Twenty healthy postmenopausal women, 48–55 years old were randomly assigned to receive either a 4-h naloxone infusion at 2 mg/h (group 1, n = 7) or a 10 mg i.v. bolus of metoclopramide (group 2, n = 7) or both drugs, simultaneously (group 3, n = 6) before and after 3 weeks of transdermal estradiol (100 μg/day). Blood samples were obtained at 30-min intervals during 4 h and duplicate determinations of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂) and prolactin (PRL) were performed in all samples. Results: In group 1 only a mild but significant LH rise after but not before estrogen replacement was seen. In group 2 PRL had a greater rise after than before estrogen therapy, without other hormonal changes. In group 3 a greater rise in PRL occurred after than before estrogen administration and serum LH had a sustained rise throughout the test only after estrogen replacement (greater than in group 1). No FSH changes were observed. The after-estradiol PRL response was nearly similar in groups 2 and 3. Conclusions: Our results indicate that in the untreated postmenopausal women, the dopaminergic system has little and the opioidergic system has no significant input in the control of gonadotropin or prolactin release. However, following estrogen replacement, opioids are involved in the inhibition of LH release and stimulating PRL release, while the dopaminergic system acts to inhibit PRL release and modulates LH release or inhibition, depending on the levels of circulating estrogens.     

Effect of a conjugated oestrogen (Premarin®) cream on ageing facial skin. a Comparative study with a placebo cream

The effects of Premarin cream on ageing facial skin were studied in a randomised, doubleblind, parallel group study. Fifty-four women aged 52–70 years who had moderate to severe facial cutaneous ageing, applied 1 g of either Premarin cream (0.625 mg conjugated oestrogens per gram of cream), or placebo cream (same composition with the exclusion of conjugated oestrogens) to the face nightly for 24 weeks. Each morning these women protected their face with a sunblock SPF 15. Skin thickness was measured by B-scan ultrasonic echography, and skin microrelief by profilometry. Each subject's facial appearance was also evaluated by the subject herself and by the clinician. A statistically significant difference (P = 0.013) in favour of Premarin cream was detected in skin thickness at week 24. Skin thickness (dermal plus epidermal) for the women who used Premarin cream increased from 1.56 ± 0.20 mm at baseline to 1.68 ± 0.19 mm, compared with 1.52 ± 0.20 mm at baseline to 1.59 ± 0.19 mm in the placebo group. Premarin cream was also significantly more effective than placebo cream in improving fine wrinkles according to the results at weeks 12 and 24 (P = 0.010 and P = 0.012, respectively). Significant improvement from baseline was detected in both groups for roughness, laxity and mottled pigmentation and/or lentigines; however, there was no significant difference in these parameters between the two treatment groups. No subjects discontinued treatment for a safety reason. In conclusion, Premarin cream produced better results than the placebo cream; the difference was statistically significant for skin thickness and fine wrinkles. Premarin cream was well tolerated locally, and its general safety was good.     

继发性闭经患者血清性激素检测的临床意义

目的:探讨了继发性闭经患者血清性激素水平的变化和意义.方法:应用放射免疫分析对33例继发性闭经患者进行了血清E2、FSH、LH、PRL和P水平检测,并与30名正常健康女性作对照.结果:继发性闭经患者血清E2水平明显低于正常人组(P＜0.01),而血清FSH、LH、PRL和P水平则显著高于正常人组(P＜0.01).结论:检测继发性闭经患者血清性激素水平的变化对了解病情、指导临床实践均具有一定的临床价值.