Cenestin

Neurobiol Aging 2000 May-Jun;21(3):475-96
The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective
Diaz Brinton R, Chen S, Montoya M, Hsieh D, Minaya J, Kim J, Chu HP
Department of Molecular Pharmacology and Toxicology and the Program in Neuroscience, University of Southern California, Pharmaceutical Sciences Center, 1985 Zonal Avenue, Los Angeles, CA 90033, USA

The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women's Health Initiative. Morphologic analyses demonstrated that CEEs significantly increased neuronal outgrowth in hippocampal, basal forebrain, occipital, parietal and frontal cortex neurons. Dose-response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect with greatest potency occurring in hippocampal and occipital cortex neurons. CEES induced highly significant neuroprotection against beta amyloid(25-35), hydrogen peroxide and glutamate-induced toxicity. Rank order of potency and magnitude of CEE-induced neuroprotection in the brain regions investigated was hippocampal neurons > basal forebrain neurons > cortical neurons. In hippocampal neurons pre-exposed to beta amyloid(25-35), CEEs halted Abeta(25-35)-induced cell death and protected surviving neurons from further cell death induced by Abeta(25-35). Because CEEs are the estrogen replacement therapy of the Women's Health Initiative, results of the current study could provide cellular mechanisms for understanding effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial.

Maturitas 1999 Jun 21;32(2):87-93
Climacteric skin ageing of the face--a prospective longitudinal comparative trial on the effect of oral hormone replacement therapy
Pierard-Franchimont C, Cornil F, Dehavay J, Deleixhe-Mauhin F, Letot B, Pierard GE
Department of Dermatopathology, Belgian SSTC Research Center 5596, University Medical Center Sart Tilman, Liege

BACKGROUND: It is still a matter of debate whether HRT improves the physical quality of sun damaged skin. OBJECTIVES: To compare in a prospective longitudinal study the effects of climacteric aging controlled or not by HRT upon the tensile properties of facial skin. METHOD: A total of 140 women aged 40-52 years were enrolled in the study. The HRT group comprised 90 volunteers and a control group encompassed 50 non recipient volunteers. Yearly measurements of tensile functions of facial skin were performed for 5 years. A computerized suction device equipped with a 2-mm diameter hollow probe derived tensile variables quantifying skin distensibility, viscosity and elasticity. RESULTS: Climacteric aging was characterized by increased skin distensibility (1.1% per year) and viscosity (1.3% per year) mirrored by a decrease in elasticity (1.5% per year). HRT helped mitigate such changes. However, the HRT efficacy was not similar in all volunteers. Groups of good and poor responders were clearly identified as far as benefit on skin elasticity was concerned. CONCLUSION: The beneficial effect of HRT upon climacteric skin aging of the face is confirmed, at least in a subgroup of menopausal women.

GENERIC NAME: conjugated equine estrogens
BRAND NAME: Premarin

DRUG CLASS AND MECHANISM: Estrogens are one of the two major classes of female hormones. (Progestins comprise the second major class.) Estrogens are used primarily to treat the symptoms of menopause and states in which there is a deficiency of estrogen, for example, in women who have had their ovaries removed.

Conjugated equine estrogens are a mixture of several different estrogens that are derived from the urine of pregnant mares. Estrogens have widespread effects on many tissues in the body. Estrogens cause growth and development of the female sexual organs and maintain female sexual characteristics such as the growth of underarm and pubic hair and the shape of body contours and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium).

PREPARATIONS: Tablets: 0.3, 0.45, 0.625, 0.9, and 1.25 mg. Vaginal cream: 0.625 mg per gm of cream.

STORAGE: Conjugated equine estrogens should be stored at room temperature between 15-30°C (59-8677°F).

PRESCRIBED FOR: Conjugated estrogens are used for treating the symptoms of menopause including hot flashes, vaginal dryness, and vaginal atrophy. They also are used as therapy when the body does not produce enough estrogen due to castration, ovarian failure or underdevelopment of hormone-secreting organs (hypogonadism). Conjugated estrogens also may be beneficial in treating advanced prostate and breast cancer. Although estrogens are approved for treating osteoporosis, other drugs usually are prescribed for this purpose.

DOSING: To minimize side effects, the lowest effective oral dose of conjugated estrogens is used. The usual starting dose for treating symptoms associated with menopause and for preventing postmenopausal osteoporosis is 0.3 mg/day. The dose should be increased based on the response of patients’ symptoms.

The vaginal cream is used for treating vaginal atrophy, and the recommended dose is ½ to 2 g daily in a cyclic interval of 3 weeks on treatment and 1 week off treatment.

Hypogonadism is treated with doses of 0.3 mg or 0.625 daily with a cyclical interval of three weeks on treatment followed by one week off treatment. The dose for women who have been castrated or have ovarian failure is 1.25 mg daily in a cyclical interval of three weeks on treatment and one week off treatment. (In reality, most women take estrogens continuously since during the week off treatment, symptoms return because of the lack of estrogen.) For treatment of breast cancer the recommended dose is 10 mg daily for three months.

DRUG INTERACTIONS: Estrogens increase the liver's ability to manufacture factors that promote the clotting of blood. Because of this, patients receiving warfarin (Coumadin), a drug that thins the blood and prevents clotting by reducing clotting factors, need to be monitored for loss of the blood thinning effect if treatment with an estrogen is begun.

Rifampin (Rifadin), barbiturates, carbamazepine (Tegretol), griseofulvin (Grifulvin), phenytoin (Dilantin), St. John’s wort and primidone all increase the elimination of estrogen by enhancing the liver's ability to break-down estrogens. Use of any of these medications with estrogens may result in a reduction of the beneficial effects of estrogens. Conversely, drugs such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), ritonavir (Norvir) and grapefruit juice may decrease the break-down of estrogens by the liver and lead to increased levels of estrogens in the blood. This may result in more side effects.

PREGNANCY: Estrogens should not be given to pregnant women due to the risk of harm to the fetus.

NURSING MOTHERS: Estrogens are secreted in breast milk and cause unpredictable effects in the infant. They should not be taken by women who are breast-feeding.

SIDE EFFECTS: The most common side effects of conjugated estrogens are headache, nausea, back pain, joint pain and vaginal bleeding. Patients may also experience vaginal spotting, loss of periods or excessively prolonged periods, breast pain, breast enlargement and an increase or decrease in sexual drive. Effects of estrogen on the skin include rash, and melasma (tan or brown patches) that may develop on the forehead, cheeks, or temples and may persist even after estrogens are stopped. In the eyes, conjugated estrogens may cause an increase in the curvature of the cornea, and patients with contact lenses may develop intolerance to their lenses.

There is an increased risk of cholesterol gallstones among men and women taking estrogens. Estrogens can inhibit the flow of bile from the liver (cholestasis) and uncommonly cause jaundice.

Estrogens can cause salt (sodium) and water retention. Therefore, patients with heart failure or reduced function of their kidneys who are taking estrogens should be carefully observed for water retention and its complications.

Blood clots in the legs or lungs occasionally occur in women taking conjugated estrogens. This potentially serious complication of estrogen therapy is dose-related, that is, it occurs more commonly with higher doses. Therefore, the lowest effective doses that relieve symptoms should be used. Cigarette smokers are at a higher risk for blood clots. Therefore, patients requiring estrogen therapy should quit smoking.

Estrogens can promote a build up of the lining of the uterus (endometrial hyperplasia) and increase the risk of endometrial cancer. (Women who have undergone surgical removal of the uterus or hysterectomy are not susceptible to develop endometrial hyperplasia.) The addition of a progestin to estrogen therapy prevents the development of endometrial cancer.

The Women’s Health Initiative found that postmenopausal women (50-79 years old) taking conjugated equine estrogens, 0.625 mg daily, in combination with medroxyprogesterone, 2.5 mg daily, for five years, had an increased risk of heart attacks, stroke, breast cancer, and blood clots, while postmenopausal women taking conjugated estrogens without progesterone experienced only increased strokes but not increased blood clots, heart disease, or breast cancer. There was an increased risk of impaired cognition and/or dementia among women over age 65 who were treated with either estrogens or estrogens and medroxyprogesterone.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov
my.webmd.com