Transdermal Estradiol Patch Research Articles

Comparative bioavailability study of a matrix versus a reservoir transdermal estradiol patch in healthy postmenopausal women

The single-application bioavailability of estradiol from a new matrix (Climaderm ®) versus a standard reservoir (Estraderm ® TTS 50) transdermal therapeutic system was investigated in a prospective, open-label, randomized, two-period crossover study in healthy postmenopausal volunteers. Each system was labeled to deliver approximately 0.05 mg of estradiol per day and was applied to the abdominal area and worn continuously for 4 days; there was a minimum 5-day washout between the two study periods. For each study period, venous blood samples were obtained before patch application, during treatment (20 samples), and after patch removal (3 samples) and assayed for estradiol and estrone. In addition, the samples obtained at 0, 8, 12, 24, 48, 72, 96, and 120 hours after application were assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Twenty-six women completed both study periods. No differences between the patches were detected with regard to peak concentration and time to peak concentration. Based on area under the curve, the two patches were bioequivalent through 48 hours. From 48 to 96 hours, however, the matrix patch produced a more consistent level of estradiol. Mean values for the levels of estradiol, estrone, FSH, and LH for the entire study period are presented.

Effect of Acute Ethanol Ingestion on Prolactin in Menopausal Women Using Estradiol Replacement

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

Sequential estrogen-progestin addition to gonadotropin-releasing hormone agonist suppression for the chronic treatment of ovarian hyperandrogenism: a pilot study.

The purpose of the study was to evaluate the efficacy and safety of a sequential regimen of estrogen-progestin addition to GnRH agonist suppression in ovarian hyperandrogenism. Eight patients presenting with a polycystic ovary syndrome were treated with an sc implant of GnRH agonist every 4 weeks for 48 weeks. Starting at week 9, patients were replaced with 100 micrograms transdermal estradiol patches continuously and sequentially combined with 10 mg oral medroxyprogesterone acetate the last 2 weeks of each 4-week period. The rapid down-regulation of the pituitary-ovarian axis led to significant reduction of testosterone and androstenedione to 48.9% and 67.4% of baseline, respectively. During steroid replacement, testosterone and androstenedione continued to decrease gradually. The baseline hirsutism score (18.7 +/- 1.3) progressively fell to 9.7 +/- 2.0 at the end of treatment. The mean hair diameter was significantly reduced (0.097 +/- 0.004 vs. 0.081 +/- 0.005 mm). A withdrawal bleeding was obtained in 63.6% of the artificial cycles, but breakthrough bleeding occurred during 48% of the sequential replacements. The incidence of menopausal symptoms was low. There was a nonsignificant decrease in bone mineral content of the lumbar spine and the femoral neck but no trend in Ca2+/creatinine and OH-proline (OH-P)/creatinine ratios or in serum triglycerides and cholesterol fractions. There was a nonsignificant increase in hirsutism score in five patients followed up for 24 weeks after cessation of treatment, although there was a rapid return of hormones toward baseline and recurrence of irregular bleeding. Transdermal estradiol addition periodically combined with medroxyprogesterone acetate is effective in reducing hirsutism and is safe in minimizing side effects and bone loss. A regimen allowing a better bleeding control would make this approach a valuable alternative for prolonged or repeated palliative treatment of excessive hair growth and irregular bleeding in polycystic ovary syndrome.

Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study.

To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p < 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p < 0.01) and in the articular index (p < 0.05). There were no significant changes in ESR or CRP in either group. Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.

An Australian Experience of Transdermal Oestradiol Patches in a Subtropical Climate

Tolerability and efficacy of transdermal oestradiol patches were assessed in 121 menopausal women over a period of 3 months to 2.5 years. Of particular interest, in a subtropical climate such as Brisbane, were the problems associated with adhesiveness and skin irritation during the summer months. We conducted a retrospective study with self-administered questionnaires. All patients had been selected for the nonoral route because of side-effects or relative contraindications to oral therapy. There was, overall, good efficacy and acceptability. The majority of the women found the patch very adequate in relieving symptoms of the menopause (vasomotor, genitourinary and musculoskeletal). Most preferred the patch to oral therapy. The oestradiol patch was well tolerated and few side-effects were reported. Breast tenderness and weight gain were 2 minor problems associated with its use. Skin irritation was minimal, but adhesiveness was a problem during the summer months, especially with swimming or showering. Some practical suggestions were obtained about how to overcome site of application problems.

Endometrial effect of transdermal estradiol and progestin ST-1435 in postmenopausal women

To study the endometrial effect of the transdermal synthetic progestin ST-1435. Prospective. City Maternity Hospital, Helsinki, Finland. Eleven postmenopausal women used transdermal estradiol (E2) patches for 6 weeks immediately before a vaginal operation for prolapse. For the last 10 days, 1 mg of ST-1435 transdermally in a gel was combined to the treatment. Blood samples were taken to follow serum concentrations of E2, follicle-stimulating hormone, and ST-1435. Endometrial samples for histologic examination were collected during the operation to evaluate the effect of the progestin. Transdermal absorption of ST-1435 resulted in reasonably constant serum concentrations of ST-1435 in each subject. A progestin effect on the endometrium was seen in 9 of 10 samples obtained. One sample did not show any progestin effect in spite of adequate ST-1435 levels, but this patient's E2 concentrations were low. When the estrogen stimulation was adequate, the transdermal ST-1435 induced a progestin effect on the endometrium, i.e., it had an end-organ effect.

The effect of ketoconazole and transdermal estradiol on serum sex steroid hormones levels

In this randomized, open-label trial, 24 subjects were studied. There were 12 subjects with essential hypertension and 12 normotensive controls who received, after an initial control period, 48 h of treatment with a transdermal estradiol patch or ketoconazole tablets every 8 h for six doses, or in combination. LHRH (100 micrograms) and ACTH (250 micrograms) were given at 48 h of each treatment. Each treatment was one week apart. In both normotensive and hypertensive men ketoconazole reduced adrenal and gonadal androgens, raised 11-deoxycortisol and 17 alpha-hydroxyprogesterone levels; blunted the rise of cortisol to ACTH and had no effect on the response of LH to LHRH. Transdermal estradiol raised serum estradiol levels, blunted the time to peak plasma concentration of LH to LHRH and produced a normal response to ACTH. Although baseline level of total and free testosterone and DHEA-S were lower in hypertensive men, the response of the pituitary (LH) to LHRH and adrenal axis with ACTH were similar in both normotensive and hypertensive men. Blood pressure was unaffected by any of the treatment interventions in either normotensive or hypertensive men. Although ketoconazole or transdermal estradiol reduce androgens, there was no evidence that this reduction in androgens was involved with the short term regulation of blood pressure in hypertensive men.

TREATMENT OF SEVERE PREMENSTRUAL SYNDROME WITH OESTRADIOL PATCHES AND CYCLICAL ORAL NORETHISTERONE

40 patients with premenstrual symptoms were randomly allocated to receive placebo patches or active treatment with transdermal oestradiol patches (2 x 100 μg) to suppress ovulation. Norethisterone 5 mg was given in each group from day 19-26 of the cycle to ensure a regular withdrawal bleed. Treatment was for 6 months with crossover at 3 months. Patients completed the Moos menstrual distress questionnaire (MDQ) and the premenstrual distress questionnaire (PDQ) daily throughout the study. 5 patients withdrew, 4 because of skin reactions and 1 because of considerable improvement with initial (active) treatment. After 3 months, both groups showed improvement in MDQ and PDQ scores. In general, between 3 and 6 months, patients who switched from active treatment to placebo had deteriorating scores while patients who switched from placebo to active treatment maintained or improved upon their initial gains. Significant improvements occurred after changing to active treatment in five of six negative MDQ symptom clusters and in six of ten PDQ symptoms.

A randomized comparison of nonoral estradiol delivery in postmenopausal women

We compared the transdermal and subdermal routes of estrogen administration with respect to the constancy of estrogen delivery and metabolic effects. Twenty postmenopausal women were randomized to receive either two 25 mg estradiol pellets subdermally (n = 10) or a 0.1 mg estradiol transdermal patch twice weekly (n = 10). Blood was sampled at 0, 2, 4, 6, 8, 12, 24, and 72 hours and 1, 2, 4, 8, 12, 16, 20, and 24 weeks (fasting samples at 0, 12, and 24 weeks), and a fasting urine was obtained after diuresis at 0, 12, and 24 weeks. In a 72-hour profile, serum estradiol levels (mean ± SE) were highest at 24 hours (179 ± 20 pg/ml) and fell to 139 ± 16 pg/ml at 72 hours in the pellet group. In the patch group, estradiol levels rose rapidly to 152 ± 33 pg/ml at 4 hours, remained relatively constant over 8 hours, and fell to 46 ± 10 pg/ml at 72 hours. At 1 week, estradiol levels in the pellet group were 113 ± 12 pg/ml and remained relatively constant for 24 weeks. In contrast, estradiol levels in the patch group were 52 ± 11 pg/ml at 1 week and then varied widely until 24 weeks, when the levels were 89 ± 26 pg/ml. The mean estradiol/estrone ratio ranged between 1 and 2.5 in both groups but fluctuated widely in the patch group. Follicle-stimulating hormone was suppressed in both groups; however, the decrement in the pellet group was greater (p < 0.002). There was a significant increase in high-density lipoprotein cholesterol and a decrease in total cholesterol/high-density lipoprotein cholesterol at 12 weeks with the pellet but only at 24 weeks with the patch. The urinary calcium /creatinine ratio was reduced more consistently with the pellet than with the patch. Hot flushes were eliminated in all subjects.

Suppression of ovulation by transdermal oestradiol patches.

Suppression of ovulation by transdermal oestradiol patches.