General Information

Cenestin has been approved to reduce moderate or severe menopausal symptoms.

Estrogens are hormones made by the ovaries of normal women. Between ages 45 and 55, the ovaries normally stop making estrogens. This leads to a drop in body estrogen levels which causes menopause (the end of monthly menstrual periods). If both ovaries are removed during an operation before natural menopause takes place, the sudden drop in estrogen levels causes surgical menopause.

When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating (hot flashes). Using estrogen drugs can help the body adjust to lower estrogen levels and reduce these symptoms. Most women have only mild menopausal symptoms or none at all and do not need to use estrogen drugs for these symptoms. Others may need to take estrogens for a few months while their bodies adjust to lower estrogen levels. The majority of women do not need estrogen replacement for longer than six months for these symptoms.

Clinical Results

A randomized, placebo-controlled multicenter clinical study was conducted evaluating the effectiveness of Cenestin for the treatment of vasomotor symptoms in 120 menopausal women. Patients were randomized to receive either placebo or 0.625 mg Cenestin daily for 12 weeks. Dose titration was allowed after one week of treatment. The starting dose was either doubled (2 x 0.625 mg Cenestin or placebo taken daily) or reduced (0.3 mg Cenestin or placebo taken daily), if necessary.

Efficacy was assessed at 4, 8 and 12 weeks of treatment. By Week 12, 10% of the study participants remained on a single 0.625 mg Cenestin tablet daily while 77% required two (0.625 mg) tablets daily. The results indicate that compared to placebo, Cenestin produced a reduction in moderate-to-severe vasomotor symptoms at all time points

Side Effects

In addition to the risks listed above, the following side effects have been reported with estrogen use:

• Nausea and vomiting
• Breast tenderness or enlargement
• Enlargement of benign tumors of the uterus (fibroids)
• Retention of excess fluid
• Spotty darkening of the skin, particularly on the face

CONTRAINDICATIONS

Estrogens should not be used in individuals with any of the following conditions:

• Known or suspected pregnancy (see PRECAUTIONS)
• Undiagnosed abnormal genital bleeding
• Known or suspected cancer of the breast (except in appropriately selected patients being treated for metastatic disease)
• Known or suspected estrogen-dependent neoplasia
• Active thrombophlebitis or thromboembolic disorders

Mechanism of Action

DESCRIPTION

Synthetic conjugated estrogens, A tablets contain a blend of nine (9) synthetic estrogenic substances. The estrogenic substances are sodium estrone sulfate, sodium equilin sulfate, sodium 17a-dihydroequilin sulfate, sodium 17a-estradiol sulfate, sodium 17b-dihydroequilin sulfate, sodium 17a-dihydroequilenin sulfate, sodium 17b-dihydroequilenin sulfate, sodium equilenin sulfate and sodium 17b-estradiol sulfate.

Additional Information

Estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 µg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.

Circulating estrogens modulate the pituitary secretion of the gonadotropins, leutinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism and estrogen replacement therapy acts to reduce the elevated levels of these hormones seen in postmenopausal women.