Endometrial safety of low-dose vaginal estrogens.

ABSTRACT: It is estimated that up to 50% to 90% of postmenopausal women may experience genitourinary syndrome of menopause (GSM), which may have a detrimental impact on quality of life. One of the most effective modes of treatment of GSM is low-dose vaginal estrogens. Numerous studies have addressed the safety of these estrogens using endometrial biopsy and/or endometrial thickness on ultrasound. Based on these studies, the consensus is that low-dose vaginal estrogens do not substantially increase the risk of endometrial hyperplasia or cancer; however, the data are severely limited by short duration of follow-up. Although long-term trials are warranted, they are difficult to carry out, costly, and will not yield data for years. More immediate information regarding endometrial safety may be obtained from studies measuring endometrial tissue and serum concentrations of estradiol, estrone, and relevant equine estrogens after administration of different estrogen formulations and doses. This would allow us to understand better the metabolism of estrogens by the vagina and endometrium, and how much estrogen is reaching the endometrium. Here, we discuss metabolism, receptor binding, and signaling of estrogens in vaginal and endometrial tissue, and summarize the existing studies on the endometrial impact of low-dose vaginal estrogen treatment in postmenopausal women.

Effect of oral contraceptives on total and bioavailable 25-hydroxyvitamin D.

Studies show an increase in circulating levels of 25-hydroxyvitamin D [25(OH)D] in women using combined oral contraceptives (COCs). 25(OH)D is a quantitatively important metabolite and widely used clinical marker of vitamin D status and is regulated by vitamin D binding protein (VDBP). However, studies have not identified the type of formulations used by the women, and there are no data on the effect of progestins on 25(OH)D levels. Our study objective was to compare the effects of two COC formulations [ethinyl estradiol (EE)/norethindrone acetate (NETA) vs. EE/levonorgestrel (LNG)] as well as LNG alone on total and bioavailable (free plus albumin-bound) 25(OH)D levels in serum samples collected at baseline, mid treatment, and end of treatment. Total 25(OH)D and VDBP were measured by immunoassay, and bioavailable 25(OH)D was calculated. The results show that with the EE/NETA formulation, total and bioavailable 25(OH)D and VDBP levels increased non-significantly by 7.4 %, 14.9 %, and 10 %, respectively, from baseline to end of treatment. In contrast, the corresponding changes with EE/LNG showed an increase of 4.4 % in total 25(OH)D but a significant decrease of 18.2 % in bioavailable 25(OH)D and increase of 19.1 % in VDBP. When LNG was administered alone, no significant changes were observed in total and bioavailable 25(OH)D or VDBP levels during the course of treatment. Our findings show considerably different effects on total and bioavailable 25(OH)D levels, as well as VDBP levels, with different oral contraceptive formulations. LNG may have a suppressive effect on VDBP, similar to its well-known androgenic effect on SHBG. Further studies are needed to determine the effect of hormonal contraceptive formulations on vitamin D status and its potential impact on women's health.