Charcoal treatment and risk of escape ovulation in oral contraceptive users

Ovulatory potential was studied during the use of two oral contraceptive pill preparations, after repeated mid-cycle administration of activated charcoal. Eleven women used monophasic pills containing gestodene, 75 microgram, plus ethinyl oestradiol, 30 microgram, or norethisterone acetate, 1 mg, plus ethinyl oestradiol, 30 microgram, for 4 months each, in randomized order. During both pill treatments the third cycle was a control cycle, and during the fourth cycle of both pill types, 5 g of activated charcoal was ingested four times a day, starting 3 h after pill intake, on cycle days 12, 13 and 14. Ovarian activity was monitored by intravaginal ultrasonography of follicles and by measurements of serum concentrations of LH, FSH, oestradiol and progesterone throughout the control and charcoal-treatment cycles of both pill treatments. None of the women ovulated. Follicular activity seen in two women did not correlate with charcoal administration. It is concluded that the possible enterohepatic recirculation of gestodene and norethisterone is not of clinical importance. Repeated charcoal treatment, when administered 3 h after but at least 12 h before pill intake, can be used to treat diarrhoea in women taking oral contraceptives.     

A comparison of effects of sequential transdermal administration versus oral administration of estradiol plus norethisterone acetate on serum NO levels in postmenopausal women

AIM: To compare the effects of sequential transdermal administration versus oral administration of estradiol plus NETA on serum nitric oxide (NO) levels in postmenopausal women (PMW). MATERIALS AND METHODS: Eighty postmenopausal subjects without any prior hormone replacement therapy (HRT) usage were enrolled in this study. All participants were healthy, ambulatory, non-smoker and had similar life styles with dietary habits. HRT was given to participants according to desired HRT administration, in group A (n=50); oral estradiol hemi-hydrate (2 mg)/norethisterone acetate (1 mg), and in group B (n=30); transdermal combined patch comprising estradiol (0.05 mg) alone and estradiol (0.05 mg)/norethisterone acetate (0.25 mg), were given sequential for 12 months. Serum NO levels were studied using Total Oxide Assay Kit (Assay Designs, Inc.) according to manufacturer's instructions prior to and after 12 months from the HRT treatment. RESULTS: The mean serum NO levels prior to the HRT in groups A and B was 0.48+/-0.46 (range, 0.27-0.76 nmol/mL) nmol/mL and 0.47+/-0.48 nmol/mL (range, 0.29-0.693 nmol/mL) (p>0.05). The mean serum NO levels after the HRT in groups A and B was 0.53+/-0.33 nmol/mL (range, 0.29-2.10 nmol/mL) and 2.91+/-0.50 nmol/mL (range, 2.10-3.67 nmol/mL) (p<0.05). A significant difference was found between mean serum NO levels prior to and after the treatment in group B (p<0.05). CONCLUSIONS: Transdermal sequential combined HRT with estradiol hemi-hydrate/NETA was found to be superior to sequential combined oral HRT in increasing serum NO levels.     

The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy

Objective: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. Method: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density<100 mg/cm³) and treated with oral E+P plus alendronate 10 mg/day. Result: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P<0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P>0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P>0.05) but NTx excretion diminished more in patients with high baseline levels. Conclusion: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration.     

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 microg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.     

Combination therapy of low-dose medroxyprogesterone acetate and oral estrogen does not affect endothelial function in the forearms of postmenopausal women

OBJECTIVE: We investigated whether low-dose medroxyprogesterone acetate (MPA) combined with oral estrogen had adverse effects on endothelial function compared with oral estrogen alone in postmenopausal women with mild hypercholesterolemia. DESIGN: Subjects were divided into two groups. One group received conjugated equine estrogen (CEE, 0.625 mg daily) orally for the first 3 months, followed by estrogen combined with MPA (2.5 mg daily) orally for an additional 3 months ( = 26). The other group received no treatment (control group, = 12). Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Nitrite/nitrate, angiotensin-converting enzyme, and lipid concentrations were measured in the serum. RESULTS: Both CEE and CEE combined with MPA significantly increased the FBF during reactive hyperemia. This increase was similar in both active treatment phases. No changes were seen in controls. FBF after sublingual nitroglycerin did not change over 6 months in either group. Significant and similar increases in serum concentration of nitrite/nitrate and plasma renin activity as well as decreases in angiotensin-converting enzyme activity were found in both treatment phases. No such changes occurred in the control group. There was no significant increase in high-density lipoprotein cholesterol or decrease in low-density lipoprotein cholesterol between the treatment phases. Likewise, no such changes were observed in the control group. CONCLUSIONS: Our 6-month study suggests that the addition of low-dose MPA with CEE had no adverse effects on forearm resistance artery endothelial function compared with CEE alone.     

Oral contraceptives and tryptophan metabolism: Effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone

The effect upon tryptophan metabolism of the use of combined oestrogen-progestagen oral contraceptives containing a low (0.05 mg) dose of oestrogen, or of the continuous administration of megestrol acetate, has been studied by determining the excretion of tryptophan metabolites in urine collected after a 2 g oral dose of the amino acid.An investigation of 10 women before being given oral contraceptives and after 21 days and three months of their use showed that xanthurenic acid excretion is increased within 21 days and that by three months the urinary levels of xanthurenic acid, kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid may all be elevated.Ten other women studied after taking a combined type of oral contraceptive for six months or longer excreted significantly higher levels of all four metabolites than did those who had been treated with these steroids for only three months. The abnormal urinary excretion of tryptophan metabolites was completely reversed by treatment with pyridoxine hydrochloride, 20 mg daily for one month.Studies of four women when they were taking an oestrogen-containing oral contraceptive and at intervals after they had discontinued its use showed that abnormal tryptophan metabolism may persist for three months or longer.Megestrol acetate, a progestagen used as an oral contraceptive, was found to have no significant effect upon tryptophan metabolism.The possible clinical significance of the effects of oral contraceptives upon tryptophan metabolism is discussed.     

Endometrial and menstrual response to subcutaneous oestradiol and testosterone implants and continuous oral progestogen therapy in post-menopausal women

A regimen of subcutaneous implants of oestradiol and testosterone in combination with continuous oral norethisterone (0.35mg to 5mg daily) was used to treat 71 non-hysterectomised post-menopausal women for up to 30 mth in an attempt to avoid the withdrawal periods associated with conventional cyclical therapy, while at the same time protecting the endometrium from oestrogenic overstimulation. Amenorrhoea, defined as no vaginal bleeding for at least 3 mth, occurred immediately in 5.4–55.6% of women, the percentage depending on the daily dose of the progestogen. In those women who bled, the dose of norethisterone was adjusted at 3-mth intervals. Despite this protocol, only 51.0% of the patients were amenorrhonic after 6 mth, and 63.2% after 1 yr. Although eight women did develop amenorrhoea for 12–27 mth, there was a high drop-out rate by the others, mainly because of unacceptable irregular bleeding. Irrespective of the bleeding pattern, endometrial biopsies 6 mth after treatment revealed endometrial atrophy. It is concluded that this form of therapy is inferior to oral continuous combined hormone replacement where amenorrhoea can almost invariably be achieved.     

Antioxidant effect of short-term hormonal treatment in postmenopausal women

OBJECTIVES: Recent studies have shown that estrogens alone or in association with progestins can exert an antioxidant effect on Low-Density Lipoprotein (LDL) and lipids of platelet membranes. It has been demonstrated that the oxidative modification of LDLs also involving the formation of lipid peroxides, exerts several biological effects that may contribute to the onset and progression of cardiovascular diseases. Therefore, the aim of our study was to evaluate the effect of short-term treatment with oral estrogens alone and estrogens plus progestin on endogenous and copper-induced serum levels of lipid peroxides in postmenopausal women. METHODS: Thirty-nine postmenopausal women were randomly divided into three groups: group I was treated with oral conjugated equine estrogens (CEE) for 21 days; group II received oral CEE for 21 days and, after 14 days of this treatment, 5 mg/day of medrogestone was added for 7 days; group III did not receive any therapy (controls). Endogenous and copper-induced serum levels of lipid peroxides were determined before and after 21 days of treatment in the two treated groups and in the control group. RESULTS: The serum endogenous levels of lipid peroxides in postmenopausal women did not change after short-term treatment with hormone replacement therapy. Moreover, copper-induced serum levels of lipid peroxides significantly decreased after therapy in both groups I and II. CONCLUSIONS: Our data show that hormone replacement therapy (HRT) inhibits lipid peroxidation and may play a role in preventing cardiovascular diseases.     

Behavioral effects of ethynyl estrogens in the female rat

The synthetic analogues of estradiol, ethynyl estradiol and mestranol, are used in oral contraceptives. Their effects on food intake and sexual behavior were evaluated in female rats, and compared with those of estradiol. It was found (Experiment 1) that both ethynyl estradiol and mestranol reduced food intake reliably, and more than estradiol. Water intake and body weight followed similar trends. Ethynyl estradiol, but not mestranol, plus progesterone stimulated proceptive and receptive behavior in ovariectomized female rats. Daily administration of ethynyl estrogens without progesterone showed similar trends (Experiment 3). It is hoped that these studies provide guidelines for further work on the effects of synthetic estrogens on sub-primate and primate behavior.     

Oral contraception, ovarian disorders and tobacco in myocardial infarction of woman

In Italy, two cases of myocardial infarction in women who smoked are reported: one used oral contraceptives and the other had abnormally high serum progesterone. The first case was a 35-year old woman who smoked 35 cigarettes daily, and had suffered from exertional angina for a year. She took oral contraceptive containing 0.125 mg levonorgestrel and 0.05 mg ethinyl estradiol. Her lipid and carbohydrate findings were normal. She died 4 days after hospitalization, and necropsy revealed a transmural infarction and an occlusive thrombus. The second woman, 40 years old with a habit of smoking 20 cigarettes daily, was admitted with acute myocardial infarction and fibrillation. She had hypercholesterolemia (280 mg%) and elevated enzymes, PMNs and sedimentation rate. Her progesterone level was 33 ng/ml (normal range 3-25 ng/ml. After removal of an aneurysm, she recovered.     

Comparison between 1 year oral and transdermal oestradiol and sequential norethisterone acetate on circulating concentrations of leptin in postmenopausal women

BACKGROUND: Oral and transdermal postmenopausal hormone replacement therapy (HRT) affects lipid and glucose metabolism differently, which is of significance in the release of leptin by adipocytes. Moreover, oestrogen and progesterone can stimulate leptin secretion in women of reproductive age. Therefore, we compared the effects of oral and transdermal oestrogen plus progestin regimen on plasma leptin in 38 healthy postmenopausal women with normal body mass index (BMI), who wished to use HRT to control incapacitating climacteric symptoms. METHODS: The women were randomized to treatment with oral HRT (2 mg oestradiol on days 1--12, 2 mg oestradiol plus 1 mg norethisterone acetate (NETA) on days 13--22, and 1 mg oestradiol on days 23--28, n = 19), or with transdermal HRT (50 microg/day of oestradiol on days 1--13, and 50 microg oestradiol plus 250 microg/day NETA on days 14--28, n = 19) for 1 year. Plasma samples were collected before and at oestradiol + NETA phase after 2, 6 and 12 months treatment and were assayed for leptin. RESULTS: The baseline leptin, ranging from 3.3 to 34.9 microg/l, was significantly associated with BMI (r = 0.78, P < 0.0001 ), but showed no difference between women in oral HRT (geometric mean 13.9 microg/l, 95% confidence interval (CI) 10.1--17.6 microg/l) or transdermal HRT group (geometric mean 12.0 microg/l, 95% CI 9.7--14.3 microg/l). Neither oral nor transdermal oestradiol + NETA caused any significant changes in plasma leptin (or BMI) after 2, 6, or 12 months of treatment. CONCLUSION: Leptin is an unsuitable factor to detect oestradiol + NETA-induced metabolic changes in postmenopausal women.     

Long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with uterine leiomyomas

BACKGROUND: Our aim was to evaluate the long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with symptomatic uterine leiomyomas. METHODS: Fifty pre-menopausal women with uterine leiomyomas were treated with leuprolide acetate depot at dose of 3.75 mg/28 days and raloxifene hydrochloride at 60 mg/day for 18 cycles. At admission and after each six cycles of treatment, bone mineral density (BMD), uterine, leiomyoma and non-leiomyoma dimensions, serum bone metabolism markers, lipid, glucose and insulin levels were evaluated. Leiomyoma-related and climacteric-like symptoms were assessed using a daily diary. RESULTS: Throughout the study, no significant change in BMD or in any bone metabolism markers was observed. A significant decrease in uterine, leiomyoma and non-leiomyoma sizes was detected in comparison with baseline already after 6 months. No other significant change was observed at the successive follow-up visits. No significant change in lipid and glucose profile was detected throughout the study. The treatments were well tolerated. All treatment withdrawals (16%, eight out of 50) were due to lack of compliance, and none to drug-related adverse experiences. CONCLUSION: GnRH agonist plus raloxifene administration is an effective and safe treatment for pre-menopausal women with uterine leiomyomas.     

Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins.

To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation.     

Effects of RU16117, an orally active weak oestrogenic compound,in postmenopausal women

Daily oral administration of 1, 3 or 10 mg of RU16117 (11α-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 ± 17.0, 35.1 ± 9.1 and 20.1 ± 2.8% of control (pretreatment values, P < 0.01), respectively, after 4 wk of drug administration. Although the pattern was similar, the inhibitory effect of RU16117 was even more pronounced on FSH than LH levels: a 50% decrease of basal LH and FSH levels was obtained at the daily 1.8 and 1.2 mg doses of RU16117, respectively. No significant change of basal serum gonadotrophin levels was observed with the daily 0.3 mg dose. Administration of 1 mg of RU16117 every second day or 10 mg once a week led to a relatively small but significant (P < 0.05) 20–25% decrease of basal serum LH levels after 4 wk of treatment in four out of five women. While daily 0.3 and 1.0 mg doses of RU16117 had no significant effect on the LH response to 100 μg LHRH, the 3.0 mg dose delayed the response up to 90 min. The 10 mg dose, on the other hand, led to a markedly delayed and reduced response. Treatment for the same period (4 wk) with 1 mg RU16117 every second day or 10 mg once a week led to a small (20–25%, P < 0.05) inhibition of the LH response to LHRH. At the dose of 10 mg once a week, RU16117 had no or minimal effect on endometrial histology. Since RU16117, an orally active weak oestrogenic compound, has been shown to have anticarcinogenic activity in the rat, the present findings suggest that this new steroid could be useful for the treatment of climacteric symptoms.     

Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries

OBJECTIVE: To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle). DESIGN: An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment. RESULTS: Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase. CONCLUSIONS: The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.     

Endometrial changes induced by the administration of an oral contraceptive, norethindrone (S-3800B)

Pathohistological studies on the effects of an oral contraceptive, norethindrone 5 mg and mestranol .05 mg, on the endometrium during and after the administration of the drug are reported. Menstrual cycles with biphasic temperature patterns returned within 2 to 3 cycles after discontinuing the drug. No significant side effects were recognized. During treatment, the endometrium became markedly atrophic and the stroma showed marked edema. Endometrial glands were poorly developed at the first cycle; glands were frequently cystic. Blood vessels had marked thickening of their walls from the twelfth cycle on. The lumen of the lymphatic vessels was markedly dilated. No mitotic activity was seen in glandular or stromal cells.     

In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.

The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-risk lipoprotein pattern in post-menopausal women on sequential oestrogen/progestogen treatment

Female hormones are known in influence serum lipoproteins. In post-menopausal women oestrogens decrease the concentration of low-density lipoprotein (LDL) and increase that of high-density lipoprotein (HDL), while progestogens may have the opposite effect. The risk of coronary heart disease (CHD) should consequently be decreased by oestrogens and increased by progestogens. We report here the changes observed in serum total cholesterol, triglycerides, and lipoproteins in post-menopausal women during sequential oestrogen/progestogen treatment. Oestriol and 17 beta-oestradiol were given alone for the first 12 days, in combination with norethisterone acetate (1 mg/day) for the next 10 days, and then in reduced amounts for the last 6 days of the 28-day cycle. Three different doses of the oestrogens were investigated (high, medium and low). A total of 177 normal post-menopausal women volunteered for random allocation to treatment or placebo groups. Blood samples were taken every 3 mth during the progestogen phase of the cycle. Serum total cholesterol was found to be 10-13% lower over a 3-yr period on the high oestrogen dose and 5 and 3% lower on the medium and low doses, respectively. No significant changes were seen in serum triglycerides. Determination of lipoprotein fractions showed that the reduction in total cholesterol was due to reduced LDL-cholesterol, the HDL-cholesterol levels remaining virtually unchanged.     

Effect of losartan on sodium appetite of hypothyroid rats subjected to water and sodium depletion and water, sodium and food deprivation

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg x g(-1), the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg x g(-1) did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors.     

A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women

OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on the vaginal blood flow and sexual function in postmenopausal women with previous hysterectomy. DESIGN: Fifty-seven women were randomized to receive either oral (0.625 mg of conjugated equine estrogens per tablet; n = 27) or topical (0.625 mg conjugated equine estrogens per 1 g vaginal cream; n = 30) estrogen administered once daily. All women underwent estradiol measurements, urinalysis, pelvic examination, introital color Doppler ultrasonographies, and personal interviews for sexual symptoms using a validated questionnaire before and 3 months after ET. RESULTS: A higher serum level of estradiol was noted in the oral group compared with the topical group after 3 months of ET. There were significant increases in the number of vaginal vessels and the minimum diastole (P < 0.01), and marked decreases of pulsatility index values (P < 0.01) in both groups after ET. Regarding the systolic peak, we found a significant decrease only in the topical group (P < 0.05). Although the post-ET prevalence of anorgasmia decreased significantly in both groups (P < 0.05), changes in other domains, including the rates of low libido and coital frequency, were not statistically significant (P > 0.05). In the topical group, ET improved sexual function on the vaginal dryness and dyspareunia domains in a statistically significant manner (P < 0.05), but this was not the case in the oral group (P > 0.05). However, the efficacy of oral ET for vaginal dryness and dyspareunia reached 80% and 70.6%, respectively. The corresponding figures of the topical ET were 79.2% and 75%. CONCLUSIONS: The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function, but it may not have an impact on diminished sexual desire or activity. Compared with systemic therapy, topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol.