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Objective: We evaluated the acute effects of low-dose oral estradiol and sequential progesterone on the insulin-like growth factor (IGF)/growth hormone (GH) axis, IGF-binding proteins (IGFBPs) 1 and 3, and plasma levels of sex hormone-binding globulin (SHBG) in postmenopausal subjects., Study Design: Thirty healthy normal-weight women (mean age: 54.2 +/- 5.7 years) spontaneously postmenopausal for at least 6 months were enrolled. None had used hormone replacement therapy (HRT). Appropriate investigations excluded renal, glucose, lipid and coagulation abnormalities. Breast X-ray and endometrial ultrasound examinations excluded organic pathologies. They received oral cyclical HRT for 1 year, based on the administration of oral estradiol (1 mg/day) for 28 consecutive days plus progesterone (200 mg/day) from day 15 to day 28; out of the whole group, 15 subjects received progesterone orally (group A), while in 15 progesterone was administered transvaginally (group B). On the day before treatment (T0), on day 14 (T14) and on day 28 (T28) of the first cycle, plasma levels of estradiol, progesterone, SHBG, GH, IGF-I and -II, IGFBP-1 and -3, insulin and C-peptide were assayed in all patients. The same parameters were evaluated at T14 and T28 during the 12th month of treatment., Results: At T14, we observed significant increases in the levels of estradiol (from 20 +/- 16 to 115 +/- 71 pg/ml, p < 0.001), SHBG (from 132 +/- 42 to 182 +/- 55 nmol/l, p < 0.001) and IGFBP-1 (from 92 +/- 57 to 127 +/- 87 ng/ml, p < 0.004), while the level of IGF-I decreased (from 197 +/- 138 to 129 +/- 85 ng/ml, p < 0.003). At T28, progesterone levels were significantly higher in the women receiving it orally than transvaginally (8.4 +/- 6.1 vs. 3.7 +/- 3.2 ng/ml, p < 0.025). However, while oral progesterone did not affect the estrogen-induced variations, transvaginal progesterone abrogated the increase in the levels of IGFBP-1. The levels of IGF-II, IGFBP-3, GH, glucose, C-peptide and insulin did not change at any time. At 1 year, the values maintained the same trends. The estrogen-induced variations of SHBG were correlated directly with those of estradiol (r = 0.48) and inversely with those of IGF-I (r = -0.424)., Conclusions: Low-dose oral estradiol reduces plasma levels of IGF-I and increases IGFBP-1 and SHBG concentrations, while GH is unchanged. These effects, significant and immediate, lead us to hypothesize a direct action of estradiol on hepatocytes.

Objectives: To investigate the effects of transdermal estrogen replacement therapy (ERT) on plasma homocysteine levels in postmenopausal women who underwent total hysterectomy with bilateral oophorectomy., Methods: In two-phase open longitudinal prospective study we compared 28 premenopausal women and 35 healthy postmenopausal patients to evaluate the effect of transdermal estrogen treatment (TTS 50 twice-weekly) on plasma homocysteine levels after 6 and 12 months of therapy., Results: The study showed statistically relevant differences (P<0.05) in baseline plasma homocysteine concentration between the patients in premenopausal and in postmenopausal status. No difference in the plasma homocysteine levels was observed after 6 and 12 months of ERT on postmenopausal patients., Conclusions: Surgically postmenopausal women have higher plasma homocysteine concentrations than premenopausal women, but transdermal estrogen treatment for 12 months in postmenopausal women does not modify homocysteine levels.

We studied 18 early (6 to 36 months) postmenopausal patients with a mean age of 51 years (47-53), who had never undergone hormone replacement therapy before and had no contraindications to hormone replacement. All cases of menopause were spontaneous. The treatment consisted in the continuous transdermal administration of 17-beta-estradiol (50 microg/daily) by skin patch to be replaced every 84 hours. The patients were further treated with a two-week progestogen administration every fortnight. This consisted of transdermal norethisterone acetate (0.25 mg/daily) combined with estradiol in the same patch in the first year, and oral dihydrogesterone (10 mg/daily) in the second year, without wash-out period. Before treatment (T0), and at the 12th (T1) and 24th (T2) month we measured the body mass index, the arterial blood pressure (AP), lipoproteins, coagulation parameters and bone metabolism parameters. The systolic pressure presented mean values (+/-SD) equal to 128.5+/-10.2 mmHg (T0), 131.1+/-7.4 mmHg (T1) and 130.4+/-7.5 mmHg (T2). Diastolic pressure values showed mean value ranging from 85.4+/-8.7 mmHg (T0) to 83.9+/-5.3 (T1) and 83.4+/-5.8 mmHg (T2). The detailed analysis of values of triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B and coagulation parameters at different times of therapy showed no statistically significant changes. With regard to bone metabolism, no statistically significant changes from baseline values were observed in parathormone, alkaline phosphatase, calcitonin, urinary calcium/creatinine ratio, and bone mineral content expressed by the bone density.

In this study we evaluated different metabolic parameters and bone mass, before and after 18 months of treatment by transdermal estradiol associated with oral sequential MPA in menopause. We treated 46 physiologically postmenopausal patients (44-55 years old) for at least six months, by TTS/E2 50 mcg for 3 weeks and MPA 10 mg for the last 12 days of estradiol treatment. The fourth week was free of therapy. Before treatment and after 18 months, we evaluated bone density (BMC/BW), body mass index (W/sqH), systolic and diastolic blood tension, lipid parameters, coagulation parameters, mineral metabolism with statistical elaboration of our results. After therapy we found a significant decrease in diastolic blood tension, a significant reduction in triglyceride levels and a slight but significant increase in HDL-cholesterol levels. The only variation in coagulation parameters was a decrease of circulating fibrinogen. No variation occurred in the body mass index, mineral metabolism or bone density. In conclusion even long term transdermal treatment seems metabolically well tolerated and very useful in relieving neurovegetative climacteric symptoms and dystrophic genital ones.

The Authors compare E2 and Progesterone plasma levels in the luteal phase of twelve normally menstruating women whose basal body temperature curves were biphasic and in which breast micronodularity and mastodynia were present, with those of ten breast disease-free controls. The significant difference (p less than 0.001) found in Progesterone levels gives strength to the opinion that Progesterone supply therapy can effectively improve both mastodynia and the clinical picture objectively documented.

As breast dysfunctional pathology does not appear constantly correlated to significant variations of steroid plasma levels, we purposed to verify whether the control of tissutal mechanism of hormone vehiculation can provide more reliable informations, in order to identify early endocrine disorders and to check more properly the effectiveness of the treatment from both a qualitative and a quantitative standpoint. In this view we assayed the receptors for estradiol and progesterone in the endometrium of women with mastodynia and healthy controls, to verify whether endometrial tissue receptivity may be useful in the control of breast tissue receptivity; in fact, both the tissues are hormone-dependent and equally exposed to the hormones of the menstrual cycle.