Transdermal Treatment Research Articles

Coagulation factors in postmenopausal women using hormone replacement treatment

SummarySummaryProthrombin fragment F1 + 2 and thrombin-antithrombin complexes (TAT) were measured in 97 postmenopausal women, either untreated or stabilised on subcutaneous depot, oral or transdermal hormone replacement treatment. Thirty-two used depot, 34 transdermal or oral hormone replacement and 31 were untreated. Control, oral or patch and depot groups had mean (± s.d.) Fl+2 levels of 1·25±0·40, 1·13±0·31 and 1·11±0·31 nmol/l, and mean TAT levels of 2·1±0·76, 2·03 20·61 and 1·75±0·63 nmol/l respectively. Oestradiol levels were elevated in both treatment groups compared with controls (P < 0·001). Although oestradiol levels were supraphysiological in 22/32 (62 per cent) of women using depots and 6/19 (32 per cent) of women using oral hormones, no relationship between F1 + 2 and TAT and oestradiol was observed.

Transdermal treatment with clonidine—a new approach in the management of hypertension

Transdermal treatment with clonidine—a new approach in the management of hypertension

Effects of oophorectomy and hormone replacement therapy on plasma lipids

The aim of this study was to determine the effects on plasma lipids and lipoproteins of oophorectomy and various hormone replacement therapy (HRT) delivery systems using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day). A total of 90 women completed the l-year follow-up period. Patients were randomly assigned to five groups. The first ( n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second ( n = 20) 50 μg/day transdermal oestradiol cyclically and the third ( n = 15) 0.625 mg/day CEE continuously. These three groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group ( n = 20) received 0.625 mg/day CEE and 2.5 mg/day MPA continuously, while the fifth ( n = 19) constituted a treatment-free control group. After oophorectomy patients showed increases in low-density lipoprotein (LDL), apolipoprotein B and the atherogenic index, whereas after HRT patients exhibited falls in plasma LDL, apolipoprotein B and the atherogenic index and increases in high-density lipoprotein (HDL) and apolipoprotein A1. No significant changes in total cholesterol were observed after surgery or treatment and decreased levels of triglycerides were detected only in the transdermal treatment group.

Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen

Abstract OBJECTIVE: Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. STUDY DESIGN: A behavioral stress test was given to premenopausal ( n = 13) and postmenopausal women ( n = 36). Biophysical and neuroendocrine responses were measured during and on completion of the stress test. The postmenopausal women were then randomized to placebo or transdermal estradiol treatment for 6 weeks, at which time another behavioral stress test was given. RESULTS: Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women ( p \lt 0.05). On retesting, significant biophysical responses that were present during the initial stress testing were still present ( p \lt 0.05) in the placebo group but were blunted with estrogen treatment. Plasma corticotropin, cortisol, androstenedione, and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women; this response was maintained after placebo treatment. Postmenopausal women treated with estrogen had blunted responses. CONCLUSION: Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women. The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women. Estrogen appears to blunt the stress-induced response. (AM J OBSTET GYNECOL 1992;167:1831-6.)

Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition.

Follicular recruitment takes place under FSH stimulation at the end of the luteal phase and the beginning of the subsequent follicular phase, the so-called luteal-follicular transition (LFT). Inhibin, a known suppressor of FSH, has been implicated in the onset of the rise in FSH levels, as the fall in its immunoreactive plasma levels after the demise of the corpus luteum has been shown to correlate negatively with the increase in FSH. To analyze the role of estradiol (E2), another inhibitor of FSH secretion in the LFT, we designed an experimental paradigm to dissociate the physiological falls in inhibin and E2. This was achieved by extending the duration of luteal plasma E2 levels with transdermal E2 treatment. Untreated ovulatory cycles in seven healthy female volunteers, aged 28-38 yr, were compared with E2-treated cycles in the same subjects, with treatment starting on the 10th day after the LH surge and continuing through the 4th day of the following menses [either 0.2 mg (n = 6; G1) or 0.1 mg (n = 6; G2) E2 daily]. Blood samples were obtained daily from the LH surge until the 11th day of the next cycle. Immunoreactive plasma inhibin levels reached a nadir on day 2 of menses regardless of whether women received E2. Plasma E2 (mean +/- SEM) levels remained within the normal luteal range (220 +/- 51 to 635 +/- 279 pmol/L) until the end of the treatment period in G2 (range, 253 +/- 40 to 382 +/- 62 pmol/L), but not in G1 (range, 598 +/- 195 to 1835 +/- 1259 pmol/L). However, the onset of the FSH rise was clearly delayed, from a mean of 2 days before menstruation in the controls to day 4 of the cycle in G1 and G2. Peak plasma FSH levels were attained within 6 days in the controls and within 2 or 3 days in both treatment periods. Our data suggest that it is the decrease in plasma E2 rather than inhibin that is the triggering signal for the LFT rise in plasma FSH. The exact roles of inhibin and other gonadal proteins (e.g. activins) in follicular recruitment remain to be determined.

Pharmacokinetics of a Transdermal Nicotine Patch Compared to Nicotine Gum

AbstractA new transdermal nicotine delivery system (TBS-NCT)was investigated in laboratory and clinical studies with healthy cigarette smokers. Plasma nicotine concentration time profiles were characterized during and after 24-hr application of three doses of TBS-NCT and during and after a 6-hr regimen of nicotine polacrilex gum. Pharmacokinetic analysis revealed dose-related plasma concentrations for transdermal treatments, bracketing the concentrations obtained from nicotine gum. The TBS-NCT system was also well tolerated during a subsequent 4-week open trial and demonstrated a 40% success rate for smoking cessation during the course of the trial. Overall, the TBS-NCT system appears suitable for once-daily application as an aid in smoking cessation treatments.

92006438 Cyclic hormonal replacement therapy after the menopause: Transdermal versus oral treatment

92006438 Cyclic hormonal replacement therapy after the menopause: Transdermal versus oral treatment

Transdermal oestrogen replacement therapy in a Finnish population

In an open, multicentre study, transdermal administration of oestradiol (E 2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and 83.5% sweating before therapy, only 5.7% and 11.8%, respectively, reported these symptoms at the end of the trial. Furthermore, 97.6%, 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patients completing the treatment, of whom 78% were willing to continue the treatment after the trial. These results show that transdermal administration of E 2 is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermal treatment to be superior to their previous oral replacement therapy.

Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: a multicentric study

Eighty-eight patients (84 men and 4 women; mean age 59.3 years) with stable exercise-induced angina pectoris were enrolled in this within-patient, placebo-controlled study aimed at comparing the efficacy of the continuous and intermittent (12 hour on, 12 hour off) application of transdermal nitroglycerin. Eighty-one patients completed the study. After a 1-week placebo run-in period, during which the stability of angina was assessed on a bicycle ergometer, the patients received continuous treatment (two 10 mg 24 hour patches twice daily, at 8 a.m. and 8 p.m.), intermittent treatment (two 10 mg 24 hour patches at 8 a.m. and two placebo patches at 8 p.m.) and placebo (two placebo patches twice daily, at 8 a.m. and 8 p.m.), each given for one week in a double-blind randomised sequence, according to a 3 × 3 latin-square design. A cycloergometric exercise test was performed at the end of each period of treatment, 4 and 10 hours after the application of the morning patch. In comparison with placebo, both schedules of the active treatment induced a significant increase in both the ischemic (duration of exercise to 1 mm ST segment depression) and the angina threshold (duration of exercise to mild angina) at the 4th and at the 10th hours after-dosing. A significant difference was also found between continuous and intermittent treatment at the same times of observation, in favour of the intermittent schedule. The limited number of anginal attacks recorded during placebo prevented any clinical evaluation of the treatments. This study shows that the efficacy of transdermal nitroglycerin is more pronounced when it is given following an intermittent schedule. The overnight nitrate-free interval does not lead to increased cardiovascular risk in patients with stable exercise-induced angina.

EFFECT OF TOLERANCE TO GLYCERYL TRINITRATE ON VASCULAR RESPONSES IN CONSCIOUS RABBITS

1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings. 2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10-40 micrograms/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5-20 micrograms/kg per min i.v.) and acetylcholine (ACh, 3-12 micrograms/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN-induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh. 3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN-tolerant rabbits contractile responses to serotonin or the thromboxane-mimetic U46619 were significantly attenuated, in contrast to the responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) which were significantly enhanced. 4. Similarly, in conscious rabbits, PE-induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the alpha 2-adrenoceptor agonist BHT 920 were unaffected. 5. In conclusion, tolerance to GTN does not affect endothelium-dependent vasodilatation but does cause a selective enhancement of alpha 1- but not alpha 2-adrenoceptor-mediated vasoconstriction.

Transdermal and Oral Clonidine

The antihypertensive efficacy and side effects of transdermal clonidine (Catapres-TTS) and oral clonidine in equivalent doses on a weight basis were compared under double blind (double dummy) and cross over conditions in 16 outpatients with mild to moderate hypertension. After four weeks of placebo TTS and placebo tablet treatment, the patients were randomly placed into groups for six weeks of active treatment and, after an intervening week of placebo treatment, a second six week treatment period. Transdermal clonidine reduced supine and standing blood pressures (P less than 0.01) and heart rates (P less than 0.05) compared with the values at the end of the placebo periods, while oral clonidine did so to the extent of supine systolic blood pressure (P less than 0.01) and standing heart rate (P less than 0.05), respectively. There were, however, no differences in the values between transdermal and oral clonidine at the end of these six week periods. The plasma clonidine concentration was lower 12 hours after a dose of oral clonidine than after transdermal clonidine (P less than 0.05). The side effects did not differ. Seven patients said afterwards that they preferred the transdermal treatment, two preferred the oral treatment and four could not state any preference. It is concluded that transdermal clonidine is similar in its effect to oral clonidine in mild to moderate hypertension. Transdermal clonidine once a week may increase patients' compliance with antihypertensive treatment.

90056814 Effects of transdermal 17β-estradiol treatment and naloxone infusion on gonadotropin response to gonadotropin-releasing hormone in postmenopausal women

90056814 Effects of transdermal 17β-estradiol treatment and naloxone infusion on gonadotropin response to gonadotropin-releasing hormone in postmenopausal women

Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women : Clin. Endocrinol.; 30/3 (241–249)/1989/

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P less than 0.001). Both treatments reduced plasma FSH; from 42 +/- 10 (SE) IU/l to 30 +/- 2 IU/l with oral and from 46 +/- 7 IU/l to 28 +/- 6 IU/l with transdermal treatment. Urine calcium excretion fell from 0.41 +/- 0.06 (molar ratio to creatinine) to 0.17 +/- 0.02 with oral and from 0.25 +/- 0.06 to 0.13 +/- 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone. Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin-D-binding globulin and sex-hormone-binding globulin. We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side-effects without conferring additional benefit.

Atrial natriuretic peptide in the fetus.

Comment This study showed an unexpectedly high rate (10%) of allergic contact dermatitis to transdermal hyoscine in healthy men treated for several months. Allergic contact dermatitis (type IV delayed hypersensitivity) was diagnosed by well established clinical criteria and was further confirmed by the absence ofany reaction to a placebo patch. Our results contrast with those of studies conducted by the manufacturer (Alza Corporation, California, United States), in which no delayed contact sensitisation occurred. In those studies 203 subjects were examined according to a protocol that included the consecutive application of nine hyoscine patches and the application of a tenth patch after two weeks' rest. The design of these studies, however, does not rule out the possibility of delayed type IV hypersensitivity occurring as a result of more prolonged use of transdermal hyoscine. Studies of the long term use of transdermal clonidine showed an incidence of allergic contact dermatitis of 10-38% after three to 12 months of continuous treatment.3 On the other hand, delayed hypersensitivity to transdermal glyceryltrinitrate, which is commonly used in long term and repeated regimens, is rare. We conclude that delayed hypersensitivity may be a serious disadvantage of giving drugs transdermally. Evaluation of new transdermal treatments should exclude the possibility of delayed hypersensitivity, which in our experience may develop even after several months of repeated application.

Transdermal Treatment: Convenient but for Selected Use Only

Transdermal Treatment: Convenient but for Selected Use Only

COMPARISON OF THE EFFECTS OF ORAL AND TRANSDERMAL OESTRADIOL ADMINISTRATION ON OESTROGEN METABOLISM, PROTEIN SYNTHESIS, GONADOTROPHIN RELEASE, BONE TURNOVER AND CLIMACTERIC SYMPTOMS IN POSTMENOPAUSAL WOMEN

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P less than 0.001). Both treatments reduced plasma FSH; from 42 +/- 10 (SE) IU/l to 30 +/- 2 IU/l with oral and from 46 +/- 7 IU/l to 28 +/- 6 IU/l with transdermal treatment. Urine calcium excretion fell from 0.41 +/- 0.06 (molar ratio to creatinine) to 0.17 +/- 0.02 with oral and from 0.25 +/- 0.06 to 0.13 +/- 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone. Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin-D-binding globulin and sex-hormone-binding globulin. We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side-effects without conferring additional benefit.

Transdermal Clonidine Treatment for Mild Hypertension

Transdermal Clonidine Treatment for Mild Hypertension

Transdermal Treatment for Hypertension

Transdermal Treatment for Hypertension

Physiological function of connective tissue polysaccharides.

Physiological function of connective tissue polysaccharides.