L. Zanotti

Oophorectomy and Spine Bone Density: Evidence of a Higher Rate of Bone Loss in Surgical Compared with Spontaneous Menopause

To compare the influence of spontaneous and surgical menopause on bone loss, we measured with dual x-ray absorptiometry (DXA) the spinal bone mineral density (BMD) in 513 women recruited at the Menopause Clinic at Ferrara University Hospital. One hundred one women were premenopausal with regular menstrual cycles; 185 women were perimenopausal with irregular periods or with absence of menstruation for <11 months; 160 women had spontaneous menopause with at least 12 months of amenorrhea; 67 women had a surgical menopause (hysterectomy with bilateral oophorectomy) prior to which they had regular menstruation. To minimize the age bias on BMD, all postmenopausal patients were selected to have the age range at menopause corresponding with the chronological age range (45–53 years) of premenopausal women used as reference. Moreover, to evaluate the influence of time since menopause on BMD, all postmenopausal women were stratified in five categories according to time lapsed since their last menses or oophorectomy. BMD values of spontaneous and surgical menopause do not appear to differ significantly (0.908 4pM 0.146 and 0.885 ± 0.129 g/cm2, mean ± SD). However, the difference between the menopausal groups becomes evident when BMD results take into account the interval since menopause. After 61–144 months of amenorrhea, women who had undergone spontaneous menopause had a cumulative bone loss of 21.8% in comparison with premenopausal BMD, whereas women who had undergone surgical menopause had a bone loss of 25.8%. The yearly percentage of bone loss values of surgical menopause (ranging from 3.72 to 7.93) settled to ∼1% per year after 5 years from oophorectomy, whereas the percentage values of spontaneous menopause (ranging from 1.75 to 4.65) settled to 1% per year after 3 years since the last menses. The difference between bone loss rates of spontaneous and surgical menopause, evaluated by comparison of regression coefficients (— 0.027 and —0.051, respectively) of linear regressions of BMD values on time since menopause, was statistically significant (p ≤ 0.001). Odds ratio (OR) of osteopenia (as Tscore, ≥ — 1) was significantly higher in surgical menopause (OR, 10.36; CI, 24.69–4.34) compared with spontaneous menopause (OR, 7.11; CI, 14.73–3.43). Our data support the evidence that women undergoing bilateral oophorectomy while still menstruating are at a higher risk of osteopenia than women undergoing menopause spontaneously.

Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium.

We evaluated bleeding pattern and endometrium following the administration of two of the most common types of progestogens used in hormone replacement therapy, medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients in spontaneous menopause were randomly allocated to two groups. Group 1 (n = 14) received 5 mg/day of of MPA and group 2 (n = 14) received 5 mg/day of medrogestone: both the progestogens were sequentially added for the last 12 days of a 21-day period of transdermal estradiol administration (50 micrograms per day). A 7-day treatment-free period completed the cycle. The study treatments were administered for 6 cycles. The endomtria were checked for their thickness by transvaginal ultrasound before starting treatment and at 6th treatment cycle (days 6-10 of the estrogen-only phase and during the period between days 8 and 12 of the progestogen addition). Endometrial biopsies were performed before starting treatment only in the patients with a positive progesterone challenge test and in all the patients at the end of the study during the addition of the progestogen. The bleeding pattern was closely monitored. MPA is accompanied by a thick endometrium with full secretory transformation in all cases. On the contrary, the same dose of medrogestone induced a consistent decrease of estrogen primed endometrium with only 4 cases of full secretory transformation. Four medrogestone-treated patients dropped out due to unscheduled bleeding. A low dose of medrogestone added to transdermal estradiol induced incomplete transformation of endometrium and oligo-amenorrhea more frequently than MPA, but it increased the chances of irregular bleeding. MPA fully transformed the endometrium: periods were thus heavier but regular. None of the patients in either group had endometrial hyperplasia.

Hormonal Replacement Therapy and Lipids: Is Transdermal Norethisterone Acetate Better Than Oral Medroxyprogesterone Acetate?

Abstract: We evaluated the effect of transdermal norethisterone acetate (NETA) versus oral medroxyprogesterone acetate (MPA) on the lipids of 28 postmenopausal women taking hormonal replacement therapy for climacteric symptoms. All the 28 patients were using conventional patches releasing 0.050 mg of estradiol per day continuously. However, while one group of 14 patients received transdermal NETA (0.25 mg/day) for 14 days of the cycle, the other group of 14 patients received oral MPA (10 mg/day) for the same number of days. The patients were randomly allocated to one of the two groups. The treatment cycles were repeated for 12 months. There was no significant difference between the two treatment groups for compliance and for incidence of side effects. Both hormonal replacement therapies were equally effective in relieving climacteric symptoms. All the patients underwent serum lipid assays twice, the first time before starting treatment and then again during the progestogen phase of the 12th and last cycle. Serum total cholesterol (TC), low-density lipoprotein (LDL-C), and triglyceride levels did not change significantly during both treatments. Transdermal estradiol associated with oral MPA significantly reduced high-density lipoprotein (HDL-C) by 17.9% (p < 0.05) and significantly increased LDL-C/HDL-C and TC/HDL-C risk ratios by 61.7% (p < 0.05) and 33.1% (p < 0.05), respectively. In contrast, administration of the transdermal NETA did not significantly affect HDL-C levels (– 1.9% of decrease) and, consequently, the risk ratios were minimally altered, with 3.3 and 6.0% increases for TC/HDL-C and LDL-C/HDL-C, respectively. There was a statistically significant difference (p < 0.05) in HDL-C net changes between MPA and NETA treatments (+ 8.5 and - 8.0 mg/dl, respectively). We can therefore conclude that the association of transdermal NETA with transdermal estradiol elicits a relatively benign impact on lipoprotein profile in comparison to oral MPA association