Low-dosed solid oral dosage forms for hrt

Abstract

The present invention relates to a very low-dosed dosage form for hormone replacement therapy (HRT). More particularly, the present invention concerns a solid oral dosage form comprising about 0.5 mg estradiol and about 0.25 mg drospirenone, and at least one pharmaceutically acceptable excipient. Despite the very low E2 and DRSP doses it has surprisingly been found that a high proportion of the women suffering from moderate to severe hot flushes actually respond to this treatment. Accordingly, the dosage form of the invention may be used as maintenance HRT or may be used already when HRT is initiated.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a very low-dosed dosage form for hormone replacement therapy (HRT). More particularly, the present invention concerns a solid oral dosage form comprising about 0.5 mg estradiol (abbreviated “E2”) and about 0.25 mg drospirenone (abbreviated “DRSP”), and at least one pharmaceutically acceptable excipient. Despite the very low E2 and DRSP doses it has surprisingly been found that a high proportion of the women suffering from moderate to severe hot flushes actually respond to this treatment. Accordingly, the dosage form of the invention may be used as maintenance HRT or may be used already when HRT is initiated.BACKGROUND OF THE INVENTION[0002]Estrogens, and in particular E2, have been used for decades for treating estrogen deficiency symptoms, i.e. vasomotor symptoms. Hot flushes are the most common and bothersome clinical symptom of menopause, affecting approximately 75% of postmenopausal women (Sterns et al. Lancet 2002; 36...

AI Technical Summary

Benefits of technology

[0013]The present inventor has now surprisingly found that an E2 dose previously believed to be too low, is effective in providing a rapid and adequate relief of moderate to severe vasomotor symptoms if such a low E2 dose is combined with a low dose of DRSP. As will be apparent from the examples provided herein, it has surprisingly been found that a high proportion of women suffering from moderate to severe hot flushes responded to treatment with a solid oral dosage form comprising a low dose of E2 (about 0.5 mg), when combined with a low dose of DRSP (about 0.25 mg).

[0014]Accordingly, such dosage forms effectively provide adequate relief of moderate to severe vasomotor symptoms, in particular moderate to severe hot flushes, in postmenopausal women already within the first few weeks of treatment. Such a low-dosed dosage form can thus be used to initiate hormone replacement therapy or, alternatively, as maintenance therapy. Furthermore, the very low-dosed dosage forms of the invention improves the bleeding behavior, in particular it lowers the frequency of breakthrough bleedings (increases the incidence rate of amenorrhea).

[0019]In another aspect, the present invention relates to a solid oral dosage form according to the invention for lowering the frequency of breakthrough bleedings, or increasing the incidence rate of amenorrhea, in a woman.

[0021]In yet another aspect, the present invention relates to a method for lowering the frequency of breakthrough bleedings, or increasing the incidence rate of amenorrhea, in a woman, said method comprising administering a dosage form according to the invention to a woman in need thereof.

Problems solved by technology

Menopausal symptoms cause discomfort and distress, ranging from tolerable to, at times, severe enough to affect a woman's quality of life.

Also, the loss of endogenous estrogen during menopause accelerates the risk for chronic diseases, such as osteoporosis (Slemenda et al.

Conversely, a higher dose of 2 mg E2 is effective for symptom relief, but is associated with increased estrogen-related adverse events.