Efficacy on climacteric symptoms of a new estradiol transdermal patch with active matrix in comparison with a reference reservoir patch. Two long-term randomized multicenter parallel-group studies.
METHODS
Two randomized prospective multicentre parallel group studies were performed (one in Germany and the other in Italy) in symptomatic postmenopausal women. The goal was to assess the efficacy on climacteric symptoms and the safety of a new estradiol (CAS 50-28-2) transdermal patch with solid active matrix (SAM) in comparison to a conventional liquid reservoir (LR) type estradiol transdermal patch. Both patches released 50 micrograms/day estradiol. One group of patients received the SAM patch and the other the LR patch in 4-week cycles, with a twice-weekly application of the patches for 3 weeks, followed by one week without patches. Progestin opposition was achieved with medroxyprogesterone acetate 5 mg/day orally in the last 11 days of patch application in the German study and with 10 mg/day in the last 12 days of patch application in the Italian study. Both studies were divided into two Parts: Part 1 with three 4-week cycles for a total of 12 weeks and Part 2 for other ten 4-weeks cycles in which the patches could be applied also continuously. The total duration of the study was therefore 52 weeks.


RESULTS
Germany study. 133 patients resulted randomized to the SAM group and 129 to the LR group. Both estradiol patches quickly relieved climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the Kupperman Index. At the end of Part 1, in the SAM group 91% and in the LR group 96% of patients reported relief from climacteric symptoms. At the end of Part 2 the percentages were 98% and 95%, respectively. The two patches were therapeutically equivalent with a power greater than 99.7%. Both patches were systemically fairly well tolerated. Only 4.5% of patients in the SAM group and 3.9% in the LR group discontinued prematurely for possible adverse reactions related to estradiol. There was no significant difference between the two patches with regard to systemic tolerability. Conversely, with regard to local skin reactions, the SAM patch was significantly (p < 0.01) better tolerated than the LR patch. The adhesion to the skin of the SAM patches was better than that of the LR patches. RESULTS. Italian study. 139 patients resulted randomized to the SAM patch and 128 to the LR patch. Also in this study both types of patches relieved the climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the visual analogue scale (VAS) recordings of severity of hot flushes and of sweats. At the end of Part 1 both patches relieved 95% of patients from climacteric symptoms. At the end of Part 2, i.e. after 52 weeks, 100% of patients were relieved from climacteric symptoms. Of these, 72% in the SAM group and 78% in the LR group reported complete disappearance of symptoms. Also in the Italian study, therefore, the two patches were found therapeutically equivalent. Both patches stopped or even reversed bone mineral loss in L2-L4 and had some favorable effects on lipid metabolism. Both patches were systemically equally fairly well tolerated with premature discontinuations for systemic adverse drug reactions in only 5.0% of patients in the SAM group and 3.9% in the LR group. Conversely, as in the German study, the SAM patches were significantly better tolerated by the skin (p < 0.0001).


CONCLUSIONS
The two types of estradiol transdermal patches were equivalent in providing an effective and rapid relief from climacteric symptoms. Systemically both patches were fairly well tolerated. The SAM patches were significantly better tolerated by the skin. The better local tolerability combined with better adhesion and cosmetic properties render the SAM patches very patient friendly and improve the compliance in the long term estrogen replacement therapy required to reduce osteoporosis and cardiovascular risks.
Rovati
L C
LC
Department of Clinical Pharmacology, Rotta Research Laboratorium, Monza, Italy.
Schmid
K
K
Giacovelli
G
G
Bonn
M
M
Setnikar
I
I
Wolff
F
F
Genazzani
A R
AR
D000268:Adhesiveness; D000279:Administration, Cutaneous; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D002979:Climacteric / Q000187:drug effects*; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000097:blood; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D014621:Vagina / Q000502:physiology
D004967:Estrogens; D008055:Lipids; D004958:Estradiol