Ethinyl Estradiol Therapy Research Articles

Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD

Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain < 2 cm/year) in group E was 152.4 ± 3.4 cm and the standard deviation (SD) was 2.02 ± 0.62 for Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm3) was significantly different from that of group L or E (0.262 or 0.262 g/cm3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.

Subsequent endocrine therapy after resistance to ethinylestradiol treatment for the late-stage metastatic breast cancer: A retrospective cohort study.

148 Background: Aromatase inhibitor (AI) is a most commonly used as the endocrine therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, estrogen additive therapy using ethinylestradiol can be useful after long-term estrogen deprivation therapies with AI. Furthermore, there is a possibility of the beneficial effect of AI or fulvestrant as a subsequent endocrine therapy after EE2 failure. Methods: Ethinylestradiol (EE2; 3mg/day, TID) therapy was performed in 20 patients with metastatic breast cancer (median; 62 years-old, the mean observation time: 13.6 months.), who were heavily treated by sequential endocrine therapies (3rd or more line) including cytotoxic chemotherapies. We examined the efficacy of a subsequent endocrine therapy of AI or fulvestrant after becoming resistance to the EE2 therapy in the patients who got the disease control by the prior EE2 therapy. The primary endpoint was clinical benefit rate (CBR) and the secondary endpoint was time to treatment failure (TTF). (Registration number; UMIN 000002831, additional analysis). Results: Median TTF of EE2 treatment was 46 weeks (23-62+, 2 cases were ongoing). The response rate was 41% (9/22), the clinical benefit rate was 50% (11/22). The stable disease (&lt; 6 months) was 18% (4/22) and another 3 cases were judged as progressive disease. Four cases withdrew due to nausea, fatigue and muscle-skeletal pain. In 20 cases progressed after disease control (SD or more) of EE2, a subsequent endocrine therapy, fulvestrant for 10 cases and AI for 10 cases, was performed. Fulvestrant group showed 50% (3 in 6) of CBR and 15 weeks (5-55+) of TTF, and AI-treated group showed 43% (3 in 7) of CBR and 19 weeks (5-33+) of TTF. Two in three cases, who became resistance to anti-estrogen treatment, got long SD by further EE2 re-therapy. Conclusions: Some cases showed clinical benefits of a subsequent therapy by AI or fulvestrant after becoming to EE2 failure. Taken together, sequential use of estrogen and anti-estrogen therapy (vice versa) could be one of the options as a salvage endocrine therapy for the patients with end-stage breast cancer.

Oral ethinylestradiol in castration-resistant prostate cancer: a 10-year experience.

To describe our 10-year experience with the use of oral ethinylestradiol in the treatment of metastatic castration-resistant prostate cancer. From February 2000 to April 2010, 116 patients with a metastatic castration-resistant prostate cancer were prospectively submitted to oral ethinylestradiol monotherapy. Inclusion criteria were: diagnosis of castration-resistant prostate cancer after failure of at least two lines of androgen deprivation therapy and radiological evidence of metastases. Exclusion criteria were: symptomatic cases with a European Cooperative Oncology Group score >2 and severe or uncontrolled cardiovascular diseases. At inclusion in the study, all patients discontinued the previous androgen deprivation therapy and started oral ethinylestradiol at the daily dose of 1 mg. Aspirin (100 mg/daily) was concomitantly given. The median ethinylestradiol therapy duration was 15.9 months (range 8-36 months), whereas the median follow up of patients was 28 months (range 13-36 months). During ethinylestradiol therapy, a confirmed prostate-specific antigen response was found in 79 patients (70.5%). The median time to prostate-specific antigen progression was 15.10 months (95% confidence interval 13.24-18.76 months). A toxicity requiring treatment cessation was observed in 26 patients (23.2%) at a median time of 16 months (mainly thromboembolism). Our 10-year experience shows that ethinylestradiol provides a prostate-specific antigen response in a high percentage of patients with metastatic castration-resistant prostate cancer. Cardiovascular toxicity can be managed through accurate patient selection, close follow up and a concomitant anticoagulation therapy.

Abstract P1-14-04: Subsequent endocrine therapy after becoming to resistance of ‘estrogen therapy’ is beneficial as a salvage treatment for the late stage metastatic breast cancer

Abstract BACKGROUND: Aromatase inhibitor (AI) is a most commonly used as the endocrine therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, estrogen additive therapy, high-dose estrogen using ethinylestradiol, can be useful after long-term estrogen deprivation therapies with AI. Furthermore, there is a possibility of the beneficial effect of AI or fulvestrant as a subsequent endocrine therapy after EE2 failure. METHODS: Ethinylestradiol (EE2; 3mg/day, TID) therapy was performed in 22 patients with metastatic breast cancer (median; 62 years-old, the mean observation time: 13.6 months.), who were heavily treated by sequential endocrine therapies (3rd or more line) including cytotoxic chemotherapies. We examined the efficacy of a subsequent endocrine therapy using aromatase inhibitor or fulvestrant after becoming resistance to the EE2 therapy in the patients who got the disease control by the prior EE2 therapy. The primary endpoint was clinical benefit rate (CBR) and the secondary endpoint was time to treatment failure (TTF). (Registration number; UMIN 000002831, additional analysis) RESULTS: Median of TTF of EE2 treatment was 46 weeks (23-62+, 2 cases were ongoing). The response rate was 41% (9/22), the clinical benefit rate was 50% (11/22). The stable disease (&amp;lt; 6 months) was 18% (4/22) and another 3 cases were judged as progressive disease. Four cases withdrew due to nausea, fatigue and muscle-skeletal pain. In 13 cases progressed after disease control (SD or more) of EE2, a subsequent endocrine therapy, fulvestrant for 6 cases and AI for 7 cases, was performed. Fulvestrant group showed 50% (3 in 6) of CBR and 15 weeks (5-55+) of TTF, and AI-treated group showed 43% (3 in 7) of CBR and 19 weeks (5-33+) of TTF. Two in three cases, who became resistance to anti-estrogen treatment, got long SD by further EE2 re-therapy. DISCUSSION: EE2 therapy could be beneficial for heavily treated metastatic breast cancer. Some cases showed clinical benefits of a subsequent therapy by AI or fulvestrant after becoming to EE2 failure. Taken together, sequential use of estrogen and anti-estrogen therapy (vice versa) could be one of the options as a salvage endocrine therapy for the end stage breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-14-04.

Prospective observational trial of re-antiestrogen therapy after becoming resistant to ethinylestradiol treatment in hormone-dependent metastatic breast cancer.

161 Background: After heavily treated estrogen deprivation therapy by aromatase inhibitors (AIs), an additional estrogen therapy may be useful in a certain condition. Furthermore, the estrogen therapy might sensitize a subsequent anti-estrogen therapy after the acquired resistance to estrogen. Methods: In the patients who obtained disease control (SD or more) by ethinylestradiol (EE2) therapy (1.5-3mg TID), the efficacy of anti-estrogen therapy using AI or fulvestrant was examined as a subsequent endocrine therapy. Primary endpoint was clinical benefit rate (CBR), and secondary endpoints were response rate (RR) and time to treatment failure (TTF). (Registration; UMIN000002831, prospective observational trial, sub-protocol analysis) Results: EE2 therapy was performed in 22 of postmenopausal breast cancer patients with ER-positive HER2-negative in primary or recurrent tumor, who had heavily pre-treated by endocrine therapies, including chemotherapies. At the median observation period of 13.6 months, RR of 41% (9/22) and CBR of 50% (11/22) were obtained (CR; 0, PR; 9, long SD; 2, SD; 4, PD; 3) and 4 patients withdrew this trial due to adverse events of early endocrine related symptoms and cerebral infarction. Although two patients were still ongoing, the median of duration of disease-control was 46 weeks (range; 23-62+). In thirteen patients who obtained disease control (SD or more) by EE2 therapy, fulvestrant for 6 patients or AI for 7 patients was used as a subsequent therapy. Fifty percent of fulvestrant group (3/6) and 43% of AI group (3/7) showed clinical benefit (PR or long SD). TTF of fulvestrant group was 15 weeks (median; range; 5-55+) and that of AI group was 19 weeks (median; range 5-33+). Furthermore, two patients who were responders to previous AI, got long SD to the subsequent EE2 re-treatment. Conclusions: EE2 therapy after resistance to estrogen deprivation therapy could be very useful, and a subsequent anti-estrogen therapy by AI or fulvestrant could be also effective in a certain condition. Thus, the changes of the endocrine environment by EE2 may induce the sensitization to hormone dependency in acquired hormone-resistant tumors. Clinical trial information: 000002831.

Anticlastogenic effect of apigenin in human lymphocytes treated with ethinylestradiol

In the present study the antigenotoxic effect of apigenin was studied against a genotoxic dose of ethinylestradiol using the damage parameters of chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and cell cycle kinetics (CCK). Human peripheral blood lymphocytes were cultured and treated with 10 μM of ethinylestradiol along with doses of 5, 10, 15 and 20 μM of apigenin. A clear decrease in the genotoxic damage induced by ethinylestradiol was observed with increasing doses of apigenin, suggesting a protective role for apigenin during ethinylestradiol therapy.

Deep Vein Thrombosis Due to Ethinyl Estradiol Therapy for Prostatic Cancer Complicated by Hyperglycemia

Deep Vein Thrombosis Due to Ethinyl Estradiol Therapy for Prostatic Cancer Complicated by Hyperglycemia

Effect ofCentella asiaticaL. extract against ethinylestradiol-induced geno-toxic damage on cultured human lymphocytes

In the present study the effect of Centella asiatica L. extract was studied against the genotoxic doses of ethinylestradiol on human lymphocytes culture. The different doses of C. asiatica L. extract i.e. 1.075×10-4, 2.125×10-4 and 3.15×10-4 g/ml were treated separately with 5 μM of ethinylestradiol. Similar treatments were given with 10 μM of ethinylestradiol. The treatments result in a significant dose dependent decrease in chromosomal aberrations and sister chromatid exchanges on human lymphocyte cultures induced by 5 and 10 μM of ethinylestradiol. The selected doses of C. asiatica L. extract were not genotoxic itself. Hence it is concluded that C. asiatica L. extract reduced the genotoxic damage during the ethinylestradiol therapy in patients and thereby reducing the chances of cancer development in humans.

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy

Objective: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. Study Design: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 μg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. Results: At 3 months, 1 mg norethindrone acetate/5 μg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P < .029) and bleeding and/or spotting (22% vs 44%; P < .001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 μg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P = .004 and P < .001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 μg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P < .05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. Conclusion: The 1 mg norethindrone acetate/5 μg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study. (Am J Obstet Gynecol 2003;188:92-9.)

HIGH DOSE ESTROGENS IN GIRLS WITH TALL STATURE INDUCE A TRANSIENT PROLACTIN INCREASE

Estrogens are a potent stimulus of prolactin secretion as illustrated by the increase during female puberty. High estrogen levels may lead to lactotroph hyperplasia and even pituitary adenoma. Prolactinoma in a girl treated with estrogens has been described (J Ped 1988, 133:337-9). Methods: In 30 girls with constitutional tall stature prolactin levels were measured before, during and, in part of them, after Ethinyl Estradiol (EE) therapy, 200 microgram/day. At the start of treatment mean age was 12.7 yrs (range 10.3-15.9} and pubertal stage was B3-B4: all were premenarcheal. Reference data were obtained from 25 healthy girls with mean age 13.4 yrs (range 11.7-15.1), pubertal stage B3-B5 and pre- or perimenarcheal. Blood was drawn between 9.00 and 12.00 am. Results: In the control group mean prolactin was 0.19 U/l (range 0.09-0.37). In the EE group mean prolactin at the start of treatment was 0.19 U/l (range 0.05-0.51), not different from the control data. On EE (3-18 months) mean prolactin significantly increased (ANOVA P<0.001). Mean values at 3,6,9,12,15 and 18 months were 0.45. 0.41, 0.40. 0.33. 0.32 and 0.30 U/l respectively. The treatment values at each time were significantly higher compared to the control values as well (Wilcoxon P<0.001). After EE discontinuation prolactin values significantly decreased to 0.14 U/l (range 0.07-0.24), not different from pretreatment or control data. Conclusion: High dose estrogen treatment results in prolactin hypersecretion, which normalizes after estrogen withdrawal. Follow-up of these girls should be done to exclude long-term consequences as hyperprolactinoma and/or prolactinoma.

Effects of ethinyl estradiol on semen quality and various hormonal parameters in a eugonadal male

To determine the influence of estrogens on male fertility. A 36-year-old eugonadal male was subjected to two different regimens of treatment with ethinyl estradiol (EE2). Sperm quality, immunoreactive luteinizing hormone (LH) and follicle-stimulating Hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), prolactin (PRL) and sex hormone-binding globulin were determined at intervals of 2 weeks for 315 days. A gender dysphoria clinic. A transsexual male nurse. It was hypothesized (and confirmed) that by comparing the effects of increasing and constant dose of EE2 on fertility parameters, differences in estrogen-sensitivity would show more clearly. Furthermore, this procedure served to find the minimal dose of EE2 for complete testicular suppression. Low doses of EE2 (20 micrograms/d) had no negative effect on sperm motility and density for a period of approximately 4 weeks, whereas high doses (60 micrograms/d) reduced motility already after a few days and led to a pronounced decrease in sperm density after 2 weeks. After discontinuation of therapy, motility normalized faster than sperm density. Under increasing doses of EE2 there was a constant decrease of FSH that occurred several weeks earlier than that of LH. Under constant dose of EE2 (60 micrograms/d) the decrease of LH was delayed (with respect to FSH) by only a few days. The decrease in T showed a stronger correlation with that of FSH than with that of LH. Volume and fructose content of the seminal fluid correlated with the decrease in T. Rebound effects were observed for FSH, LH, T, and fructose during the therapy-free interval. Ethinyl estradiol therapy had no influence on the serum concentrations of E1, E2, and PRL. Estrone was the dominant estrogen before and after therapy with EE2. Adrenal gland activity was markedly suppressed by EE2, as reflected by the decrease in DHEAS. The suppressive effect of EE2 on FSH and sperm motility was more pronounced and consistent than on LH and sperm density. The T decrease appears to be mainly caused by a direct effect of EE2 on the testes.

Increased hGH Production Rate after Low-Dose Estrogen Therapy in Prepubertal Girls with Turner's Syndrome

Low-dose estrogen therapy significantly increases radioimmunoassayable serum hGH concentrations in the prepubertal hypogonadal female. In this study, we have examined the effects of short- and long-term low-dose ethinyl estradiol therapy on the endogenous production rates and metabolic clearance rates of hGH. We used deconvolution mathematical modeling to provide quantitative estimates of individual secretory parameters and to calculate subject-specific hGH metabolic clearance rates, by using all serum hGH concentrations and their variances considered simultaneously. Nine girls with Turner's syndrome (mean age 7.7 +/- 0.5 y) were studied on three separate nights by drawing blood every 20 min from 2200 to 0800 h before (I), after 1 wk (II), and 5 wk (III) of 100 ng/kg/d ethinyl estradiol therapy orally. We found that the endogenous hGH production rate more than doubled in all patients studied after 5 wk of ethinyl estradiol therapy (194 +/- 22 (I), 290 +/- 43 (II), and 412 +/- 66 (III) micrograms/L/12 h; p less than 0.05 for I and III). The half-life of endogenous hGH was not altered in the estrogen treatment paradigm with a mean of 19 +/- 1.6 min in study I and 18 +/- 1.2 min in both studies II and III. Our results suggest that even prepubertal concentrations of gonadal steroids in the hypogonadal female may be physiologically relevant to the maintenance of normal somatotrope secretory function.

Reduced serum vitamin B12 levels during oral cyproterone-acetate and ethinyl-oestradiol therapy in women with diffuse androgen-dependent alopecia

In a group of healthy, non-vegetarian females currently being treated for diffuse androgen-dependent alopecia with 50 or 100 mg of oral cyproterone acetate for 11 days and 30 or 40 micrograms of ethinyl oestradiol for 20 days of the menstrual cycle, significant decreases in mean serum vitamin B12 (P less than 0.0001), haemoglobin (P less than 0.003) and haematocrit (P less than 0.004) values, were observed after 6 months. Serum folic acid, red-cell folate and mean cell volume remained unchanged within the normal range during this time. All patients responded to oral cyanocobalamin, or intramuscular injections of hydroxocobalamin. In patients with baseline serum vitamin B12 levels below 350 ng/l, we would suggest prophylactic cyanocobalamin concurrent with cyproterone-acetate-ethinyl-oestradiol (CPA EE2) therapy. Studies involving other dose regimens of CPA EE2 (Dianette) or cyproterone acetate alone (Androcur, Cyprostat), may require evaluation of the vitamin B12 status if treatment is to be given for periods of longer than 3 months.

Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea

The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle-stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases.

METHIONYL GROWTH HORMONE (met-GH) IN A DOSAGE OF 4 IU/m2 DAY PROMOTES GROWTH IN TURNER SYNDROME

In a Dutch multi-center study 16 girls with Turner Syndrome were treated with met-GH in a dosage of 4 IU/m2 body surface administered s.c. once a day. In girls older than 13 years low-dose ethinyl-estradiol (EE) therapy (0.1 ug/kg body weight o.d.) was added. Ages ranged from 7.9 to 15.2 years and bone age from 6.0 to 12 “years”. Heights, expressed as standard deviation scores, were between -2.5 and -5.1 (median -3.9). Endogenous GH secretion was assessed by arginine infusion, exercise test, GRF (1-29)-test and plasma SM-C/IGF-I. Mean ( ± S.D.) growth velocities were: During the first 6 months of therapy the mean ( ± S.D.) bone age (Greulich and Pyle) advanced from 9.1 (±1.2) to 9.4 (±1.2)“years” and the predicted adult height from 148.2 (±4.5) to 151.0 (±4.2) cm. The growth response (growth velocity during 9 months of therapy minus baseline) ranged from 0.8 to 7.0 cm/year and was negatively correlated with chronological age (r= -0.48, p<0.05). In the 4 girls older than 13 years, who also received EE, the growth response was 3.3 ± 0.9, compared to 4.0 ± 1.6 in younger girls. Growth response was not correlated with maximum plasma GH levels during provocation tests. Anti-GH antibodies with a binding capacity of > 0.2 U/l were found in 5 out of 10 patients. In one of them a very high value (3.7 U/l) was found.

4 Hormone replacement therapy and sexuality in women

As a result of changing expectations of sexuality, women now hope to enjoy sexual relationships well into their later years. 2 clinically important questions for both women and their physicians are: are any changes in sexual behavior to be expected with hormone depletion at the menopause; and what effects do hormone replacement therapies have on sexual response. This chapter reviews the available evidence and discusses the clinical implications. Attention is focused on the following: animal studies (nonprimates, primates, mechanism of action, and methodological considerations); the effects of depletion of ovarian hormones on human sexuality (natural menopause and surgical menopause); the effect of hormone replacement therapies (clinical trial); and clinical implications. Pronounced changes were found in female animals with oophorectomy. Normal sexual behavior could be restored in primates with administration of estradiol and progesterone in doses approximating plasma levels of hormones during the menstrual cycle. In humans bilateral oophorectomy is usually performed in conjuction with hysterectomy, making it difficult to assess the effects of hormone depletion alone. Epidemiological studies suggest a decline in female sexual interest, orgasm, and coital frequency at menopause. There have been a few double blind studies of the effect of hormone replacement therapy on sexuality. A model used extensively in animal research involved investigation of sexual behavior after oophorectomy and subsequent replacement therapy with estrogen and progesterone. The decision was made to utilize this model in order to investigate the effects of these hormones on human females. Women selected for study had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders and were aged less than 65 years. After initial assessment the women were randomly allocated to 1 of 4 medication groups: ethinyl estradiol 50 mcg; levonorgestrel250 mcg; ethinyl estradiol 50 mcg; and levonorgestrel 250 mcg--"noridol"; placebo. After the 2nd month there was a significant difference between estrogen containing compounds and the nonestrogen containing compounds for both sexual desire and enjoyment. The difference between norgestrel and the estrogen containing drugs was highly significant for sexual enjoyment. There was also significantly more vaginal lubrication reported after 2 months of ethinyl estradiol therapy than after 2 months of placebo. The highest number of orgasms occurred with ethinyl estradiol.

Some clinical effects of oestrogen-progestogen therapy in surgically castrated women

This study reports some of the effects of oestrogen and progestogen therapy. Forty-nine women who had undergone hysterectomy and bilateral salpingo-oophorectomy took part in a double blind crossover study during which they received ethinyl oestradiol 50 μg/day, norgestrel 250 μg/day, the combination of these substances “Nordiol” and placebo. Somatic complaints were assessed at monthly interviews and weight and blood pressure recorded. The addition of norgestrel to ethinyl oestradiol therapy resulted in less dryness of skin but significantly increased mastalgia and breast size. There were no significant differences between drugs on amount of facial hair, acne, arthralgia, pruritus vulvae, vaginal discharge, vaginal odour, dyspareunia, weight or blood pressure. There was a significant reduction of diastolic blood pressure with the time duration of the study.

Changes in coagulation factors in postmenopausal women on ethinyl oestradiol.

Coagulation factors II, VII, X, VII + X complex and anti-thrombin III were measured in 10 postmenopausal women before, during and after a four-month course of 20 microgram daily of ethinyl oestradiol, taken three weeks in four. Factors VII, X and VII + X complex rose significantly during treatment but only factor X levels were significantly elevated at the end of the four-month treatment period. There was no change in factor II or anti-thrombin III levels. These effects on coagulation factors during ethinyl oestradiol therapy are, in general, similar to those found during treatment with conjugated equine oestrogens and oestradiol valerate in a previous study from the same laboratory. It seems likely that equipotent doses of ethinyl oestradiol and 'natural' oestrogens have similar effects on these coagulation factors.

METABOLIC AND HORMONAL EFFECTS OF POST-MENOPAUSAL OESTROGEN REPLACEMENT TREATMENT

ABSTRACT The influence of daily oral cyclical oestrogen treatment on the plasma lipid and lipoprotein concentrations was studied in post-menopausal females. Ethinyloestradiol (EOe) 0.05 mg was administered to 20 subjects and oestradiol valerianate (OeV) 2 mg to 19 subjects. The women were investigated twice before medication and 1, 3 and 6 months after the start of treatment. During EOe therapy the total cholesterol (TC) decreased 10 per cent, high density lipoprotein (HDL)-TC and HDL-phospholipid (PL) increased 30–40 per cent, approximated low density lipoprotein (LDL)-TC decreased 30 per cent and triglyceride (TG) increased 30–40 per cent. In the OeV treated group the HDL-TC and the HDL-PL concentrations showed a mean increase of 10–15 per cent after 6 cycles. Augmented HDL-TC level and/or decreased LDL-TC level is believed to reduce the risk for the development of atherosclerotic disease. Increased TG concentration probably raises the risk for ischaemic cardiovascular disease. Thus the net effect on the development of ischaemic cardiovascular disease due to the changes of plasma lipids induced by EOe 0.05 mg can at present not be evaluated while the plasma lipid changes observed during OeV 2 mg might hypothetically retard the development of atherosclerosis. Only 10 per cent of the changes of lipid and lipoprotein concentrations could be explained statistically by their correlations to the simultaneously occurring alterations in the glucose tolerance and the concentrations of insulin and growth hormone. The dissimilar changes in the lipid parameters in the EOe and OeV groups might be explained by the different oestrogenic potency of the drugs and a dose-response relationship of oestrogen treatment on protein and probably lipoprotein synthesis.

The effect of ethinyloestradiol on calcium and phosphorus metabolism of post-menopausal women with primary hyperparathyroidism.

1. Eight post-menopausal women with primary hyperparathyroidism were given ethinyloestradiol (0.05 mg daily) and the effects on calcium and phosphorus metabolism were observed. 2. In every patient ethinyloestradiol produced a fall in fasting plasma and urine calcium. Calcium balance improved in seven patients on treatment and there was a significant fall in 24 h urine calcium in all eight patients; however, there was no consistent change in net or true absorption of calcium. 3. Ethinyloestradiol produced a small fall in the fasting plasma inorganic phosphorus and a fall in fasting urine phosphorus in seven cases. There was a decrease in 24 h urine phosphorus in seven of the eight cases, but there was no consistent effect on phosphorus absorption nor on phosphorus balance. 4. Bone mineralization rate and bone resorption rate were determined in seven of the patients. The administration of ethinyloestradiol produced a decrease in both these variables in all seven patients. 5. The 24 h urine hydroxyproline, used as an independent measure of bone resorption, decreased in all eight patients during ethinyloestradiol therapy. 6. It is concluded that ethinyloestradiol produces an improvement in calcium and phosphorus balance and a decrease in plasma calcium and phosphorus in primary hyperparathyroidism by decreasing bone resorption. 7. It is suggested that ethinyloestradiol may be used as a medical treatment for primary hyperparathyroidism in post-menopausal women who are either unsuitable for surgery or on whom operative procedures have failed, or in those cases in whom primary hyperparathyroidism is mild.