Preventive effects of transdermal administration of 17 beta-estradiol on postmenopausal bone loss: a 2-year prospective study

A 2-year prospective study was conducted on 44 early postmenopausal women to assess the effect of transdermal estradiol (TTS-E2) on vertebral bone mass. Twenty treated women and 24 untreated were studied. Treatment consisted of TTS-E2 (0.05 mg/day, 3 weeks a month) and an oral gestagen (10 days per month). At 24 months, bone mineral density, measured by Dual Photon Absorptiometry (DPA), decreased significantly in untreated women (-4.3%) (p less than 0.001), while treated women had a net gain of +5.4% (p less than 0.001). Bone turnover parameters (serum osteocalcin, urinary calcium/creatinine ratio) were significantly (p less than 0.05) reduced from the 2nd month of treatment onwards. Serum estradiol levels were sustained during the treatment and were in the range of an early follicular phase (approximately 45 pg/ml). These findings suggest that low doses of transdermal estradiol sufficient to relieve menopausal symptoms, and which, due to the association with progestogen, result in regular withdrawal bleeding, are effective in preventing postmenopausal bone loss.     

Effect of treatment with GnRH agonists on new markers of bone metabolism

To assess the utility of new markers in monitoring bone turnover during treatment with GnRH agonists, alkaline phosphatase (total and bone specific) and urinary N-telopeptides were measured. 16 women undergoing treatment with GnRH agonists for endometriosis or leiomyomas were studied before and 3 months after the onset of treatment. N-telopeptide levels increased significantly (44% of baseline, p < 0.05). Bone specific alkaline phosphatase (BALP), measured with a new ELISA assay, was more elevated (40% of baseline, p = 0.001) than total ALP (15% of baseline, p < 0.001). In conclusion, in estrogen deficiency states, urinary N-telopeptide measurements provide a quantitative measure of bone resoption. In the assessment of bone formation, BALP determination is move sensitive than total ALP and this may be clinically useful.     

Effect of estrogen replacement therapy on the serum osteocalcin level in the postmenopausal and castrated women

Osteocalcin (OC), the major noncollagenous bone protein, is a vitamin K-dependent protein which is synthesized in osteoblasts. Serum OC is increased in patients with certain metabolic bone diseases, but little is known about the effects of menopause, castration, and the estrogen-replacement therapy on serum OC. In this study, we attempted to determine the serum OC level before and after menopause and castration, and the effects of estrogen on serum OC were also studied. Mean serum OC in women who underwent menopause or castration within 5 years was 4.56 +/- 1.74 ng/ml (mean +/- SD) and the concentration was significantly higher than that of premenopausal women. Serum OC was then, transiently reduced but increased again when estrogen deprived conditions lasted for more than 10 years. Estrogen replacement therapy (conjugated estrogen 0.625 mg/day for 6 months) could decrease not only serum Ca. P and ALP but also the serum OC from 4.45 +/- 1.40 to 2.97 +/- 1.43 ng/ml (p less than 0.001). There was a significant correlation between the percent changes in serum OC and ALP before and after estrogen administration (r = 0.60, p less than 0.05).     

Fetal growth and placental function assessed by urinary estriol excretion before the onset of pre-eclampsia.

In a series of 1,316 patients with pre-eclampsia 744 had urinary estriol excretion measured before and 366 after the onset of clinical signs of the disease. Low estriol excretion had a highly significant association with fetal growth retardation and perinatal death both before and after the onset of clinical signs (p less than 0.001). As assessed by the incidences of low estriol excretion, fetal growth retardation, and perinatal wastage, pre-eclampsia of early onset (before 37 weeks) was a malignant disease in comparison with pre-eclampsia of late onset (after 37 weeks). Patients destined to develop early-onset pre-eclampsia had a high incidence of subnormal estriol excretion (25.4%; p less than 0.001). Although further deterioration of placental function occurred after the onset of clinical signs (41.3%; p less than 0.01), fetal growth and prognosis were already determined.     

Influence of estrogen replacement therapy on endogenous calcitonin production rates.

Calcitonin is now a well-accepted therapy for inhibition of bone loss, both in the first years of menopause and in established osteoporosis. However, its exact role in the pathogenesis of that disease as well as the interactions between calcitonin production and estrogen metabolism remain unsolved. In order to clarify the influence of estrogen replacement therapy (ERT) on calcitonin secretory capacity, we measured whole plasma immunoreactive calcitonin basal levels, metabolic clearance rates and production rates in a group of postmenopausal women, before and after a daily intake for 28 days of 0.625 mg/day of conjugated equine estrogens, and again 4 weeks after the withdrawal of that estrogen replacement therapy. No significant changes appeared in immunoreactive calcitonin or immunoreactive calcitonin metabolic clearance rate but the production rate significantly increased over the 28 days (mean +/- SEM, from 21.3 +/- 5.1 pg/ml to 25.2 +/- 5.9 pg/ml, p less than 0.05), and then decreased 4 weeks after therapy was withdrawn to the initial level (17.9 +/- 3.6 pg/ml). We concluded that estrogen replacement therapy significantly increases calcitonin secretory capacity. This confirms the interactions between calcitonin production and estrogen metabolism, and may provide an explanation concerning the mode of action of estrogen replacement therapy in prevention of postmenopausal bone loss.     

The measurement of secretory endometrial protein PP14 in serum from postmenopausal women receiving unopposed estrogen or continuously combined estrogen/progestogen

A highly sensitive radioimmunoassay was developed to measure the low serum concentrations of the endometrial secretory placenta protein 14 (PP14) in postmenopausal women. The assay was established by selecting optimum reaction conditions for radioactive labelling of PP14, combined with simple procedures for the purification of the labelled PP14. The PP14 assay was used in 2 groups of healthy, early postmenopausal women blindly receiving either estrogen monotherapy (n = 20, placebo n = 25) or continuously combined estrogen/progestogen therapy (n = 20, placebo n = 23). Neither of these regimens is believed to produce secretory endometrium. During the 12 months of estrogen monotherapy, serum PP14 (S-PP14) remained unchanged at 4.9 micrograms/l, when compared with placebo. Treatment with continuously combined estrogen/progestogen showed a small but significant increase in S-PP14 from 5.3 micrograms/l to 7.2 micrograms/l at 3 months. S-PP14 remained at this slightly elevated level throughout the treatment period of 24 months. Three months after hormone withdrawal, S-PP14 had returned to the pretreatment level. We suggest that S-PP14 might be a useful marker of secretory endometrium.     

Comparison of changes in biochemical markers of bone turnover after 6 months of hormone replacement therapy with either transdermal 17 beta-estradiol or equine conjugated estrogen plus nomegestrol acetate

OBJECTIVE: To compare changes in biochemical markers of bone turnover in postmenopausal women who received sequential discontinuous hormone replacement therapy (HRT) with either transdermal 17 beta-estradiol gel (group 1) or oral equine sulfoconjugated estrogen (group 2), plus nomegestrol acetate. PATIENTS AND METHOD: Prospective, open, randomized, controlled trial, conducted on 3 parallel groups of 106 postmenopausal women. All treated groups received estrogen therapy for 25 consecutive days every month. The estrogen used was either 1.5 mg/day of transdermal 17 beta-estradiol gel (group 1) [N = 42, average age (AA) = 51.6 years, average duration of menopause (ADM = 21.5 months)], or 0.625 mg/day of oral equine sulfoconjugated estrogen (group 2) [N = 39, AA = 51.3 years, ADM = 16.8 months]. In all cases nomegestrol acetate 5 mg/day was added for 12 consecutive days every month. The control group comprised 25 patients, [AA = 53.4 years, ADM = 33.7 months]. Two bone resorption markers: urinary cross-linked N-telopeptide and C-telopeptide of type I collagen (U-NTX/Cr, U-CTX/Cr), and a bone formation marker: serum bone specific alkaline phosphatase activity were measured before and 6 months after treatment start. RESULTS: Significant decreases from baseline values were observed for the 3 biochemical markers in both treated groups compared with control (P < 0.001). There were no significant differences in changes between the 2 treated groups for the 3 biochemical markers. The mean percentage change in the 3 biochemical markers was: from -9.3 to -45.5% in group 1, from -20.5 to -39% in group 2, and from -3.3 to 2% in control group. In group 1, the mean percentage decreases in U-CTX reached optimal threshold of bone turnover change (-45%) which is considered by the International Osteoporosis Foundation as clinically relevant because it predicts an increase in BMD greater than 3% when treatment is maintained over a long term. DISCUSSION AND CONCLUSION: Both treated groups induced a significant comparable decrease of bone turnover markers after 6 months of intervention, compared with control. The group treated with cyclic administration of transdermal 17 beta-estradiol (1.5 mg/day) and nomegestrol acetate (5 mg/day) showed a bone resorption markers decrease corresponding to the threshold of clinical relevance described in the international literature and predictive of positive BMD response in long term.     

The treatment of severe premenstrual syndrome with goserelin with and without ‘add-back’ estrogen therapy: A placebo-controlled study

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting ,60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily) ,Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2 ,4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2 ,4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2 ,4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.     

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.     

Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.     

Changes in spinal and femoral bone mineral density due to pelvic irradiation following oophorectomy

Since radiation therapy has been known to be a cause of bone atrophy (radiation osteopathy), it could be important whether postoperative radiotherapy in patients who have undergone oophorectomy further promotes bone mineral loss or not. Nineteen patients with stage Ib to IIb cervical cancer were studied. Eleven of the 19 patients received only surgical treatment and 8 received postoperative radiotherapy (50 grays to the pelvis and 40 grays to the lumber spine), because of the presence of advanced lesions or positive lymphnodes. A significant increase in FSH and decrease in E2 (p less than 0.01) compared to before treatment were observed in both groups. A significant increase in serum alkaline phosphatase activities (p less than 0.01), urine-calcium/creatinine ratio (p less than 0.05) and urine-hydroxyproline/creatinine ratio (p less than 0.01), which indicated high bone turnover, compared to before treatment in both groups also appeared. Although these chemical parameters in both groups changed coincidentally, the decline in spinal bone mineral density in the irradiated group was delayed at 12 months after the treatment. On the other hand, there was no difference in the changes in femoral bone mineral density in the two groups. These results suggest that radiotherapy might inhibit the bone mineral loss at the irradiated bone site even when there was an estrogen lack.     

Changes in bone mineral density and bone turnover within 12 months after oophorectomy: a prospective study compared with hysterectomized controls

Nineteen patients (pts) with stage Ib to IIb uterine cervical cancer were studied for changes in bone mineral density and bone turnover within 12 months after radical hysterectomy and pelvic lymphadenectomy. Eleven out of 19 pts also underwent oophorectomy (OX), and the other 8 pts without OX were studied as controls. A significant increase in FSH and decrease in E2 (p less than 0.01) in OX pts indicated the completeness of oophorectomy, whereas no significant change in those levels showed retained ovarian function in the controls. In OX pts significantly increased serum alkaline phosphatase (p less than 0.01), urine-calcium/creatinine (p less than 0.05) and hydroxyproline/creatinine ratio (p less than 0.01) indicating high bone turnover after the oophorectomy were observed. However, a transient but significant (p less than 0.05) rise in these levels in the 3rd month in the controls was noted. In OX pts the spinal bone mineral density (BMD) measured by dual photon absorptiometry was significantly reduced to approximately 10% (p less than 0.05) within 12 months after oophorectomy, while in the controls loss of BMD was also observed up to 6 months, and it appeared to have returned towards baseline levels at 12 months after hysterectomy. These data suggest that a rapid and considerable loss of spinal BMD was mainly accelerated by the oophorectomy, but in part was contributed to by the stress or reduced physical activity for up to 6 months after radical hysterectomy.     

Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.

OBJECTIVE: To compare the effects of a 12-week treatment with 17ss-estradiol given alone and in sequential combination with 3.75 mg of nomegestrol acetate (Naemis), or a placebo on biochemical markers of bone turnover in menopausal women. PATIENTS AND METHODS: A double-blind, randomized, placebo and estradiol-controlled multicenter study was conducted. A total of 176 patients who had been menopausal for 1-10 years, hysterectomized or not, having no contraindications to hormone replacement therapy, without any risks factors for osteoporosis, received one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E(2)) or 1.5 mg E(2)/3.75 mg nomegestrol acetate (E(2)/NOMAC). The primary efficacy variables were the change in bone markers (total alkaline phosphatase, bone alkaline phosphatase and osteocalcin; urinary type-I collagen peptides). RESULTS: The four biochemical markers decreased only in the E(2)/NOMAC group. Bone alkaline phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the E(2) group. For both active treatment groups compared to the placebo group, the changes were statistically significant after a 12-week treatment. There were no statistically significant differences between the E(2) and the E(2)/NOMAC groups except for total serum alkaline phosphatase, whose mean value decreased in the E(2)/NOMAC group but increased slightly in the E(2) group (p < 0.001). Furthermore, after a 6-week treatment, the changes in biochemical markers of bone turnover were similar to those found after 12 weeks. Safety data were satisfactory with regard to estradiol given alone or in combination with nomegestrol acetate. CONCLUSION: These results demonstrated that 1.5 mg E(2) is effective in reducing bone turnover in postmenopausal women and proved that the combination of 1.5 mg E(2) and 3.75 mg nomegestrol acetate has no deleterious effect on bone remodelling.     

Factors affecting fetal loss in induction of ovulation with gonadotropins: increased abortion rates related to hormonal profiles in conceptual cycles

Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to-estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome.     

Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study.

Secondary amenorrhea in women with normal estrogen levels increases the risk of endometrial carcinoma. Cyclical dydrogesterone induces regular withdrawal bleeding and effectively protects the endometrium of postmenopausal women receiving estrogens. In order to assess the efficacy of dydrogesterone in inducing regular withdrawal bleeds in premenopausal women with secondary amenorrhea or oligomenorrhea and normal estrogen levels, a double-blind, randomized, placebo-controlled, multicenter study was conducted in 104 women using cyclical dydrogesterone as is used for estrogen replacement therapy. Treatment consisted of dydrogesterone (10 mg/day on days 1-14 followed by placebo on days 15-28 of each cycle) given for six cycles of 28 days. The control group received placebo throughout the six cycles. Bleeding was documented by the patient on diary cards. The number of women with withdrawal bleeding during the first cycle was twice as high in the dydrogesterone group as in the placebo group (65.4% vs. 30.8%; p = 0.0004). Superiority of dydrogesterone was also observed for regularity of bleeding over the six cycles (p < 0.0001), although endometrial thickness after six cycles did not differ between the groups. In conclusion, dydrogesterone is significantly superior to placebo in inducing withdrawal bleeding, and maintaining regular bleeding, in women with secondary amenorrhea and normal estrogen levels.     

Effects of smoking on serum lipoproteins and bone mineral content during postmenopausal hormone replacement therapy

We examined the effect of smoking on the treatment response in serum estrogens, serum lipids and lipoproteins, and bone mineral content in 110 postmenopausal women treated for 2 years with either percutaneous or orally administered combined hormones or placebo and followed up by examinations every 3 months. Serum estradiol and estrone levels during oral hormone administration were lower in smokers than in nonsmokers, whereas no differences related to smoking habits were observed during percutaneous hormone administration. Serum total and low-density lipoprotein cholesterol were significantly reduced in both smokers and nonsmokers receiving hormones, but the response in smokers was only half that observed in nonsmokers (not significant). When the impact of the route of hormone administration was examined in relation to smoking habits, the response in serum total and low-density lipoprotein cholesterol in smokers receiving oral hormones was significantly lower (p less than 0.05) than that observed in nonsmokers. No differences in serum lipids or lipoproteins were observed between smokers and nonsmokers receiving percutaneous hormones. The response in bone mineral content in smokers and nonsmokers receiving percutaneous hormones and placebo was not significantly different, although the overall response differed significantly in the two groups (p less than 0.001). In contrast, the response in smokers receiving oral hormones was significantly lower than that observed in the corresponding nonsmokers (p less than 0.01). We conclude that smoking greatly affects the response on circulating levels of estrogens in postmenopausal women treated with orally administered hormone replacement therapy and that the subsequent treatment response on serum lipids and lipoproteins and on bone mineral content is reduced accordingly. The study suggests that alternative routes of administration should be considered when postmenopausal estrogen therapy is instituted in women who smoke.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

Cortical and trabecular bone mineral content in women with endometriosis: effect of gonadotropin-releasing hormone agonist and danazol

Cortical bone (distal radius and ulna) and trabecular bone mineral content of the thoracolumbar vertebrae (T-12 to L-4) were measured with single-photon absorptiometry and quantitative computed tomography, respectively, in 55 women with laparoscopically staged endometriosis before, during, and after treatment with a gonadotropin-releasing hormone agonist (GnRH-a) or danazol. Mean pretreatment potassium phosphate mineral contents of T-12 to L-4 were 174 to 201 mg/ml in stage I to IV endometriosis and were within the 100 to 115th percentile of normal women. Similarly, cortical bone mineral contents were normal and were not significantly affected by either medication. Trabecular bone decreased significantly to 92.6 +/- 1.7% (n = 11, P less than 0.001) and 92.3 +/- 2.5% (n = 7, P less than 0.01) of baseline year after 6 months and 9 months of GnRH-a treatment and remained significantly depressed at 95.8 +/- 1.9% (P less than 0.0025) and 94.8 +/- 2.5% (P less than 0.005) 6 months after stopping treatment. Thus, cortical and trabecular bone mineral contents of women with endometriosis are normal, but treatment with GnRH-a induced significant loss of trabecular bone.     

Bone mineral content in premenopausal women treated with gonadotropin-releasing hormone analogue]

To assess bone metabolism during treatment with gonadotropin-releasing hormone analogue (GnRHa), serum osteocalcin (BGP), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcitonin (CT), calcium (Ca) and phosphorus (P) were determined before and after 6 months of GnRHa treatment in 15 premenopausal women with clinically diagnosed endometriosis. The bone mineral content (BMC) of the lumbar spine (L3) was measured by single energy quantitative computed tomography in 9 women, and in 6 of these 9 women microdensitometry was performed simultaneously during the treatment. BMC decreased significantly to 92.5 +/- 6.8% (mean +/- SD) of the pretreatment value after 6 months of treatment. On the other hand, microdensitometry revealed no significant change during treatment. Serum BGP and ALP were significantly higher after 6 months of treatment than before treatment, indicating an increase in bone formation. These data indicate that the GnRHa treatment induces an increase in bone turnover and a significant bone loss.     

Rapid reduction of uterine leiomyomas with monthly injections of D-Trp6-GnRH

Ten women with intramural leiomyomas were treated with the microencapsulated GnRH analogue Decapeptyl for 24 weeks. Four (4) mg Decapeptyl was injected, starting on day 21 of the menstrual cycle, and injections were repeated every 4 weeks for a total of 24 weeks. All patients showed a marked reduction in uterine size: before treatment it measured 284 +/- 57 cm3, after 8 weeks 122 +/- 33 cm3, and after 24 weeks 89 +/- 14 cm3. LH and estradiol decreased significantly; FSH decreased but not significantly; prolactin remained almost unaltered. Serum calcium, phosphate, alkaline phosphatase and osteocalcin increased, but, since calcium excretion (and hydroxyproline excretion) remained unaltered, these changes were considered to reflect increased bone turnover rather than bone loss. From these data it is concluded that Decapeptyl is very effective in reducing uterine fibroids, that treatment can be shorter than 6 months and that measurable bone loss did not occur.