Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. (See WARNINGS, Cardiovascular Disorders and Dementia.)
The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during five years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies and WARNINGS, Cardiovascular Disorders and Malignant Neoplasms, Breast Cancer).
The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during four years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies, WARNINGS, Dementia and PRECAUTIONS, Geriatric Use.)
Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
CombiPatch® estradiol/norethindrone acetate transdermal system) is an adhesive-based matrix transdermal patch designed to release both estradiol and norethindrone acetate (NETA), a progestational agent, continuously upon application to intact skin.
In women with an intact uterus, CombiPatch is indicated for the following:
Treatment of moderate to severe vasomotor symptoms associated with the menopause.
Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
Published Studies Related to Combipatch (Estradiol / Norethindrone Transdermal)
Lipids and clotting factors during low dose transdermal estradiol/norethisterone use. [2005.04.11]
OBJECTIVE: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis... CONCLUSIONS: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.
Effects of oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate replacement therapy on platelet aggregation in postmenopausal women. [2002.08]
OBJECTIVE: To evaluate the effects of an oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate combination on platelet aggregation in post-menopausal women... CONCLUSION: Hormone replacement treatment with a 17-beta estradiol and norethindrone acetate combination either orally continuously or transdermally cyclically and sequentially does not affect platelet aggregation in postmenopausal women.
Positive effects on cardiovascular and breast metabolic markers of oral estradiol and dydrogesterone in comparison with transdermal estradiol and norethisterone acetate. [2002.04.25]
OBJECTIVES: To assess differences in two sequential combined hormone replacement therapy (HRT) products on selected cardiovascular and breast metabolic markers. The products were different concerning the route of administration of estradiol and its combined progestin, either oral or transdermal, and the androgenic properties of progestogens, respectively, dydrogesterone and norethisterone acetate... CONCLUSION: Oral estradiol sequentially combined with dydrogesterone, a non-androgenic progestogen, induced positive changes of some cardiovascular (HDL-C) and breast (SHBG and IGF-I) metabolic markers. These effects were significantly different from those obtained with a transdermal estradiol associated to an androgenic progestogen.
Low dose transdermal estradiol/norethisterone acetate treatment over 2 years does not cause endometrial proliferation in postmenopausal women. [2002.03]
OBJECTIVE: We investigated the effects of 2-year transdermal continuous combined estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) (Estragest TTS) on bleeding and on the endometrium... CONCLUSIONS: A continuous combined transdermal patch delivering 0.025 mg estradiol/day and 0.125 mg norethisterone acetate/day provided good endometrial protection. The dose maintained a consistently high rate of amenorrhea in postmenopausal women.
Comparison between 1 year oral and transdermal oestradiol and sequential norethisterone acetate on circulating concentrations of leptin in postmenopausal women. [2001.08]
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... CONCLUSION: Leptin is an unsuitable factor to detect oestradiol + NETA-induced metabolic changes in postmenopausal women.
Clinical Trials Related to Combipatch (Estradiol / Norethindrone Transdermal)
Trial to Compare the Effects of Tibolone (LivialŽ) and Continuous Combined Low-Dose Estradiol/Noresterone (ActivelleŽ) [Completed]
The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT
Efficacy and Tolerability Study of Progesterone Vaginal Tablets (EndometrinŽ) in Menopausal Women Treated by Estrogen [Not yet recruiting]
A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland [Enrolling by invitation]
Reports of Suspected Combipatch (Estradiol / Norethindrone Transdermal) Side Effects
Product Adhesion Issue (5),
Hot Flush (4),
Breast Mass (4),
Breast Tenderness (4),
Breast Cyst (3),
Breast Cancer (3),
Incorrect Dose Administered (3),
Headache (2), more >>
PATIENT REVIEWS / RATINGS / COMMENTS
Based on a total of 2 ratings/reviews, Combipatch has an overall score of 5.50. The effectiveness score is 8 and the side effect score is 7. The scores are on ten point scale: 10 - best, 1 - worst.
Combipatch review by 51 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || No Side Effects|
|Condition / reason:|| || Menopause|
|Dosage & duration:|| || 50/250 (dosage frequency: perscribed 2x per week) for the period of 6 months and still taking|
|Other conditions:|| || Reynauds Syndrome|
|Other drugs taken:|| || Multi-vitamin, calcium|
|Benefits:|| || Patient complaints prior to drug were menopause related. Inability to sleep, hot flashes, night sweats, lack of concentration (which may have been intensified by lack of sleep), loss of elasticity in the skin. Although the use of the patch has not helped improve my skin (I didn't expect it to) almost immediately sleep was restored, night sweats stopped, and concentration ability returned, although not as completely as pre-menopause.|
|Side effects:|| || The package insert warns of serious side effects such as breast cancer, cancer of the uterus, stroke, heart attack, blood clots and dementia. I had been one determined to go through menopause without the use of any hormones. However, after trying every over the counter, holistic, and wives tale cure for 5 years with no success, I wanted RELIEF. After consulting every possible option, weighing the side effects of each one carefully, the CombiPatch was the one settled upon.
I am pleased to say I haven't had one side effect of the drug beyond a sticky spot left by the patch's adhesive. Granted, it has only been 6 months since beginning treatment but the benefits and quality of daily life restored have far outweighed the risks.|
|Comments:|| || It is, to my understanding, the smallest dosage available at 50/250 and my doctor suggested I even try applying once, rather than twice per week to see if that was enough to handle my symptoms. It was. The patch is so easy. I only have to remember once per week to change it. And on the rare occasion I forget, the patch loses some of its stickiness and reminds me! Honestly, for any woman truly suffering from constant problems like mine and don't fall into a high risk category, I would wholeheartedly recommend the patch.|
Combipatch review by 54 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Moderately Effective|
|Side effects:|| || Severe Side Effects|
|Condition / reason:|| || menopause symptoms|
|Dosage & duration:|| || N/A (dosage frequency: monthly) for the period of 11 months|
|Other conditions:|| || None|
|Other drugs taken:|| || None|
|Benefits:|| || The benefits were to alleviate menopausal symptoms. It did a very good job at that.|
|Side effects:|| || Severe bleeding to the point that I was four days away from a hysterectomy. I stopped the HRT to prepare for the surgery and the bleeding subsided and eventually stopped. The hysterectomy was cancelled.|
|Comments:|| || The patch was worn on the arm.|
Page last updated: 2006-01-31