Efficacy and safety of oral estriol for managing postmenopausal symptoms
Introduction
With the increasing longevity of the population age hormone replacement therapy (HRT) has been suggested to be necessary for obtaining a better quality of life and for avoiding metabolic disturbances resulting from hypoestrogenism in postmenopausal women. It has been well established, however, that unopposed estrogen administration may contribute significantly to the development of uterine endometrial cancer [1], [2] and breast cancer [3], [4]. Although these potential risks remain controversial, the addition of sequential or combined progesterone thus has been recognized as essential during estrogen replacement therapy [5]. For obtaining a better quality of life relieving climacteric symptoms, and preventing osteoporosis and cardiovascular disease in postmenopausal women it is important to continue HRT for long period of time. Unfortunately, however, major adverse effects, including regular or irregular uterine bleeding, may impede patient compliance with long-term HRT. Consequently, the biologically weak estrogen, estriol, which has a much weaker stimulating effect on endometrial growth than E2 and does not commonly cause vaginal bleeding appears to be best suited for HRT [6]. Although estriol appears to be much safer than estrone or estradiol, its continuous use in high doses may have a stimulatory effect on both breast and endometrial tissue [7]. The efficacy and safety of orally-administered estriol in the treatment of climacteric symptoms, however, has been investigated rarely [8], [9].
The present study therefore was designed to assess various indicators of therapeutic efficacy and safety of oral estriol for treating climacteric complains in postmenopausal women.
Section snippets
Materials and methods
The study included 68 postmenopausal women ages 35–62 years (mean±S.D., 49.9±5.9 years) with climacteric symptoms, including 35 women ages 45–62 years (53.8±4.4 years) who had undergone natural menopause (time since menopause, 61.9±28.3 months, range 36–116 months) and 33 women ages 35–54 years (45.8±4.4 years) who had undergone surgically induced menopause (time since hysterectomy with bilateral oophorectomy, 50.7±9.3 months, range 36–68 months). All subjects gave written informed consent. The
Results
Of the 68 participants, 88.2% completed the 12-month trial. Eight women dropped out during the trial. Of these women, one had unexpected vaginal spottings during the third month of treatment. Three women dropped out for lack of efficacy after 3–9 months of treatment, two for self-assessed complete relief of climacteric symptoms after 5–10 months of treatment, and two for unknown reasons after 10–11 months of treatment. Unexpected vaginal bleeding for 2–3 days occurred in five women (14.3%) of
Discussion
The present study investigated the efficacy and safety of oral estriol in the treatment of climacteric symptoms in postmenopausal women. Estriol levels in postmenopausal women are likely to be low, even through the metabolic clearance rate of estriol is decreased by 13% [14]. The decrease in estriol levels probably results from the reduction in serum E2 levels, which are significantly lower in postmenopausal women than during the early follicular phase of the menstrual cycle. While
References (33)
Pharmacokinetics of oestrogens and progesterones
Maturitas
(1990)- et al.
The effect of oral estriol succinate therapy on the endometrial morphology in postmenopausal women: the significance of fractionation of the dose
Eur. J. Obstet. Gynecol. Reprod. Biol.
(1983) - et al.
Oestrogens, gonadotropins and prolactin after intra-vaginal administration of oesteriol in post-menopausal women
Maturitas
(1981) - et al.
Effect of continuous oral administration of estriol on corpus luteum function
Contraception
(1975) - et al.
Association of exogenous estrogen and endometrial carcinoma
N. Engl. J. Med.
(1975) - et al.
Increased risk of endometrial carcinoma among users of conjugated estrogens
N. Engl. J. Med.
(1975) - et al.
A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer
J. Am. Med. Assoc.
(1991) - et al.
The use of estrogens and progestins and the risk of breast cancer in postmenopausal women
N. Engl. J. Med.
(1995) - et al.
The new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effect on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding
Obstet. Gynecol.
(1992) - Ohta H, Ikeda T, Masuzawa T, Makita K, Suda Y, Nozawa S. Differences in axial bone mineral density, serum levels of sex...