Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 µg/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal ultrasound completed with suction biopsy when required. Results Both cumulative amenorrhea and no-bleeding rates increased progressively and reached 88.9% and 100.0%, respectively, by the 12th month. Isolated or repetitive episodes of bleeding, bleeding and spotting, or only spotting were reported by three, four, and 12 women, respectively. Endometrial thickness remained unaltered. Endometrium was atrophic in the seven women in whom a biopsy was performed. Conclusion The substantially reduced progestogen load determined by this combination achieved an acceptable incidence of spotting or bleeding when associated with a low estrogenic dose. There was no apparent endometrial stimulation. Additional studies are required to confirm this observation.

Several data implicate the immune system in bone lost after estrogen deficiency, however, some of the effects on the immune system of estrogen deficiency or of estrogen receptor (ER) modulation are not well established. In this study, the effect of ER agonists on the immune system in ovariectomized mice is analyzed. Mice were ovariectomized and were administered 178-estradiol (E2), raloxifene (RAL) or genistein (GEN). The effect of a 4-week treatment on bone turnover and on several parameters that reflect the status of the immune system was studied. Results show that ovariectomy provoked both uterine atrophy and thymic hypertrophy. Although RAL corrected thymic hypertrophy, only E2 corrected both. Ovariectomized mice showed increased levels of serum calcium and cathepsin K gene expression and decreased levels of serum alkaline phosphatase (ALP) activity, which suggests that there is a persistent alteration in bone metabolism. Moreover, ovariectomy increased B-cells and CD25+ cells, and decreased the percentages of T-cells and Cbfal gene expression in bone marrow (BM). All ER agonists corrected, although to different degrees, changes induced by the ovariectomy. Furthermore, results showed that it is essential to adjust ER agonist doses to avoid immunosuppression, since all ER agonists decreased BM T-cell levels.Osteoporosis is a major public health problem which is characterized by low bone mass and an increased risk of fracture. It is known that estrogen deficiency is a well-established cause of osteoporosis and a major risk factor for bone loss and fractures, whereas hormone replacement therapy (HRT) prevents, or even reverses, bone loss and reduces fracture risk (l). However, the recent Women's Health Initiative clinical study (2) shows an increase in the index of cancer appearance and cardiovascular risk in postmenopausal women taking HRT. Therefore, attention has been centered on other therapeutic possibilities with lesser side-effects. Among the products that exert their bone function through estrogen receptors (ERs), it is necessary to underscore the Selective Estrogen Receptor Modulators (SERMs) and phytoestrogens.

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In order to assess similarities and differences in women that suffer surgical versus natural menopause, a series of bone, clinical, and biochemical parameters was assayed in a clinical sample of 35 women with surgical menopause and 112 women with natural menopause. Biochemical parameters included hormones [parathyroid hormone (PTH) and the sex steroids estradiol and testosterone] and several markers of bone turnover measured in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin, total alkaline phosphatase, total and ionic calcium, phosphate, and magnesium). In addition to type of menopause, women were divided by years since menopause (ysm 2). To detect differences and relationships between variables, ANOVA, ANCOVA, and linear regression analyses were used. Only N-telopeptide, one resorption marker, was significantly affected by the variable years since menopause 2 ( P <0.01), but not by type of menopause. The age-corrected level of PTH was significantly decreased in the surgical menopause group ( P < 0.05). In conclusion, type of menopause did not impose significant differences in bone turnover markers. PTH, one powerful resorption hormone, was diminished in surgical menopause.

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