Long-term remission and recurrence rate in a cohort of Cushing's disease: the need for long-term follow-up.

OBJECTIVE: Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94% and recurrence rates between 3 and 46%, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center. METHODS: Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years. RESULTS: Thirty-five (85.4%) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5%) patients. Thirty-two (78%) patients achieved disease remission after the first treatment, 21 (65.6%) of them presented disease recurrence. Persistent disease was observed in 9 (22%) patients. Twelve (29.3%) subjects developed post-surgical adrenal insufficiency, 7 of which (70%) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol <3 µg/dl) in the immediate post-operative state. CONCLUSIONS: We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

[Increase of PTH in post-menopausal osteoporosis]. / Aumento de los valores de PTH en la mujer con osteoporosis posmenopáusica.

AIMS: Increased parathyroid values (PTH) serum values can be observed in postmenopausal women. However, the clinical repercussion and causes of this finding are poorly understood. This study has aimed to analyze the prevalence and conditions associated to the increased serum PTH levels in postmenopausal women with osteoporosis as well as their clinical characteristics. METHODS: Post-menopausal women with osteoporosis were included in the study. PTH, 25-hydroxyvitamin D (25OHD), 24-h urinary calcium, glomerular filtration rate (GFR) and calcium intake were evaluated. The prevalence of increased PTH serum values and its relationship with vitamin D deficiency and insufficiency, kidney failure, hypercalciuria and calcium intake deficiency were evaluated, these being conditions that may increase PTH secretion. RESULTS: A total of 204 postmenopausal women with osteoporosis with a mean age of 64 years were included. Increase PTH levels (>65 pg/ml) were observed in 35% and 5 women had primary hyperparathyroidism. Women with increased serum PTH levels were older (67 ± 9 years) were old than those with normal PTH levels (63 ± 11 years) (P=0.03). PTH elevation was associated to calcium intake deficiency (<800 mg/d) in 81% of the women, to a vitamin D deficiency and insufficiency in 55% and 86%, respectively, renal insufficiency in 35% and hypercalciuria in 17% of the patients. These values, however, did not differ when compared with patients with normal PTH serum levels. Serum PTH levels were related to age (r=0.19, P=0.01) but not to 25OHD or GFR values. CONCLUSIONS: One third of the post-menopausal women with osteoporosis had elevated PTH levels. This was due to primary hyperparathyroidism in 10%. The prevalence of conditions associated to the increase in PTH (reduced calcium intake, 25-hydroxyvitamin D, renal failure and hypercalciuria) is similar to that observed in women with normal PTH values.

Idiopathic osteoporosis in premenopausal women. Clinical characteristics and bone remodelling abnormalities.

OBJECTIVE: Osteoporosis is infrequent in young premenopausal women and is often associated with secondary disorders. However, idiopathic osteoporosis may be found in this setting and few data are known on this condition. Therefore, the aim of this study was to analyse the clinical characteristics and bone remodelling abnormalities in premenopausal women with idiopathic osteoporosis. METHODS: 28 premenopausal women with idiopathic osteoporosis (aged 38.3+/-7.6 years) were included. The patients had one or more fragility fractures and/or decreased bone mass (z-score <-2 in the lumbar spine or femur). In all patients, secondary causes of osteoporosis were excluded and previous skeletal fractures, family history and risk factors for osteoporosis were recorded. In addition, bone mineral density at the lumbar spine and hip, spinal x-rays, and laboratory tests including PTH, 25-hydroxyvitamin D, 1,25 (OH)2 vitamin D and urinary calcium excretion were measured. Bone markers such as serum bone alkaline phosphatase (bone AP) and P1NP, and urinary hydroxyproline (HYP), NTx and CTx were measured and results were compared with those observed in a control group of 28 healthy premenopausal women. RESULTS: 46% of the patients had previous fragility fractures, 53% had family history of osteoporosis, 36% had associated hypercalciuria and 30% had a BMI <20 Kg/m2. Patients with idiopathic osteoporosis had increased bone resorption markers (NTx and HYP) but normal bone formation markers when compared with healthy controls. No significant differences in the clinical and biochemical parameters were observed between patients with or without hypercalciuria. CONCLUSION: Young women with idiopathic osteoporosis have an increased bone resorption without changes in bone formation when assessed by biochemical markers.

Aetiology and clinical characteristics of male osteoporosis. Have they changed in the last few years?

OBJECTIVE: The aim of this study was to analyse the clinical characteristics and etiological factors related to male osteoporosis in patients attending an out-patient rheumatology department during an 11-year period (1995-2006), as well as to compare them with the observed characteristics in a previous study performed 12 years ago. METHODS: 232 males aged 21-88 (mean 56.1+/-14) with osteoporosis were included in the study. Previous skeletal fractures and family history of osteoporosis were recorded. Bone mass assessment, automated biochemical profile and hormonal measurements (including PTH, 25-OH vitamin D, cortisol, thyroid and sexual hormones) were performed on most patients as well as 24 h urinary calcium, and bone markers. In patients with idiopathic osteoporosis 1-25-OH2 vitamin D was also determined. In addition, x-rays of the spine were obtained for all patients. RESULTS: 67% of the patients had previous skeletal fractures and 51% had vertebral fractures. 57% of the patients had idiopathic and 43% had secondary osteoporosis whereas in the previous series only 22% of the patients had idiopathic disease. The most frequent causes of secondary osteoporosis were corticosteroid therapy, hypogonodism and alcoholism. 38% of the patients with idiopathic osteoporosis had associated hypercalciuria. Patients with secondary osteoporosis were older, shorter, had lower femoral neck T-score and lower serum values of 25-OH vitamin D and testosterone, as well as higher gonadotrophin and PTH values than the patients with idiopathic osteoporosis, whereas patients with idiopathic osteoporosis had higher urinary calcium and more frequent family history of osteoporosis. Hypercalciuric patients were younger, had lower lumbar BMD, higher urinary calcium and greater incidence of lithiasis than normocalciuric patients with idiopathic osteoporosis. Back pain, frequently associated with vertebral fractures, was the most common cause of referral in all groups of patients. CONCLUSION: Idiopathic osteoporosis is the most frequent cause of male osteoporosis in this study. In these patients, family history of osteoporosis and associated hypercalciuria are frequent. The most frequent causes of secondary osteoporosis in males include corticosteroid therapy, hypogonadism and alcoholism. Although clinical characteristics of male osteoporosis are similar to that previously reported, in this study the percentage of patients with idiopathic osteoporosis was higher than previously observed.

Long-lasting subclinical Addison's disease.

OBJECTIVE: To report a patient with autoimmune adrenal disease and increased ACTH with longstanding hyperpigmentation as an isolated symptom. METHODS: A 49-year-old woman requested a diagnostic work-up for hyperpigmentation initiated 9 years before, associated with increased ACTH. She was receiving replacement therapy for autoimmune hypothyroidism. Basal and dynamic tests of glucocorticoid axis, basal investigation of mineralocorticoid axis and measurement of organ specific autoantibodies were performed. RESULTS: Plasma ACTH (143 pmol/l; normal <13.2 pmol/l) and antibodies against 21-hydroxylase (115 UI/ml; normal <1) were remarkably high, thyroid peroxidase and parietal cell antibodies were positive at low titer and all additional tests were normal. CONCLUSION: Autoimmune adrenal disease can have a very long preclinical period even with high concomitant ACTH and specific antibody titers.

Bone mass improves in alcoholics after 2 years of abstinence.

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis.

The influence of a nonskeletal disease with increased connective tissue synthesis or degradation in the collagen-related markers of bone turnover has been evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81 years), a disease with increased hepatic fibrosis, often associated with osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino-terminal (PINP) propeptides of type I collagen were assessed as indexes of bone formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I collagen cross-linked N- (NTX) and C-telopeptide (CTX) were measured as markers of bone resorption. The histologic stage of the disease and serum amino-terminal propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels were higher in patients than in controls. Among the bone resorption markers, serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly higher in patients than in controls. Serum PIIINP levels were also increased in PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP levels. Serum TRAP did not correlate with collagen-related markers of bone resorption. Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with the histologic stage of the disease, but not with osteopenia measured by densitometric procedures in 22 patients. In conclusion, collagen-related markers of bone turnover do not reflect bone remodeling in PBC. The close association of these markers with PIIINP and the clinical and histologic stage of the liver disease suggests that they are influenced by liver collagen metabolism.

Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease.

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy.

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.

Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of factors associated with discontinuation.

OBJECTIVE: To evaluate prospectively the effects of long-term estrogen replacement therapy (ERT) on bone density in surgical postmenopausal women treated for 5 years with two different modalities and to determine the factors associated with discontinuation of ERT. DESIGN: We included in the present study 165 women (mean age, 46.8 +/- 4.6 years) who had undergone surgical menopause. ERT was prescribed immediately after surgery, and bone mineral density was measured at the lumbar spine before the women entered the study and at 12, 24, 36, 48, and 60 months after being included. Treated patients were assigned at random to one of two groups. The first group received conjugated equine estrogens 0.625 mg/day continuously, and the second group received transdermal 17beta-estradiol 50 mg/day continuously. Treated groups were compared with a nontreated control group. RESULTS: Our data showed that although ERT clearly protected against bone loss in women who had experienced surgical menopause, only one third of the treated patients continued ERT at the end of follow-up. The main reason for discontinuation was fear of cancer (36.1 % of cases). In addition, no differences were observed between oral and transdermal groups of treatment. CONCLUSIONS: Long-term ERT may have a protective effect against bone loss in surgically postmenopausal women; however, two thirds of treated patients discontinued therapy after 5 years and 43% of them presented a negative balance on bone mass in one or more bone density assessments. For this reason, enhancing compliance and monitoring treatment are mandatory.

Effects of a long-acting gonadotropin-releasing hormone analog on the pituitary-ovarian-adrenal axis in women with severe hirsutism.

We evaluated modifications in the pituitary-ovarian-adrenal axis in severely hirsute women after administration of the gonadotropin-releasing hormone analog (GnRHa), D-Trp-6-luteinizing hormone-releasing hormone (LHRH) (Triptorelin) in a prospective study at a tertiary hospital. A total of 20 hirsute women aged 19 to 38 years were included. Hyperandrogenism of adrenal origin was excluded in all subjects. Patients received 3.75 mg D-Trp-6-LHRH intramuscularly (Decapeptyl 3.75; Lasa-Ipsen, Barcelona, Spain). Serum levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (delta 4 An), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone-binding globulin (SHBG) were determined before GnRHa administration, 24 and 48 hours after, and on days 7, 15, 30, and 45. GnRHa suppresses FSH, LH, and E2 in all women. Unexpectedly, adrenal steroids showed a flare-up phenomenon in the first days and subsequent decrease to lower values than before GnRHa administration. SHBG showed slight changes. After GnRHa, patients showed a significant decrease in T and delta 4 An: these hormones were reduced to half the basal levels. We conclude that GnRHa can potentially be used in the treatment of hyperandrogenism to reduce androgen levels in hirsute women.

Gonadotropin-releasing hormone analog plus an oral contraceptive containing desogestrel in women with severe hirsutism: effects on hair, bone, and hormone profile after 1-year use.

To evaluate the usefulness of D-Trp-6-luteinizing hormone-releasing hormone (LHRH) (triptorelin), a gonadotropin-releasing hormone (GnRH) analog (GnRHa), plus an oral contraceptive (OC) in the treatment of severe hirsutism, a total of 48 women between 19 and 35 years of age suffering from polycystic ovary syndrome (PCOS) with severe hirsutism were studied. Hyperandrogenism of adrenal origin was excluded in all subjects. Twenty-three patients received 3.75 mg D-Trp-6-LHRH intramuscularly monthly for 1 year plus an OC containing 30 micrograms ethinyl-estradiol and 150 micrograms desogestrel. A second group of 25 subjects received an OC containing 35 micrograms ethinyl-estradiol and 2 mg cyproterone acetate (CPA). Immediately before and after months 6 and 12 of therapy, bone mineral density (BMD) and Ferriman-Gallwey scores were evaluated and follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone-binding globulin (SHBG) were determined. After 1 year of follow-up study, the combination of a GnRHa plus OC resulted in a decrease of hirsutism similar to that observed in the CPA group (41.9% v 40.5%) and in a suppression of gonadotropins and ovarian steroids in all treated women, without significant changes in bone density. The GnRHa-OC combination can potentially be used in the treatment of hirsutism and hyperandrogenism.

Menstrual history as a determinant of current bone density in young hirsute women.

There is evidence that bone mass is influenced by estrogen, declining in situations characterized by a decrease in the production of this hormone. Usually, amenorrhea and oligomenorrhea are associated with a state of hypoestrogenism, and both situations are frequent in hirsute patients. The aim of the present study was to analyze the relationship between bone mass and menstrual cyclicity in hirsute women. A total of 52 nulliparous women complaining of hirsutism in various degrees with associated oligomenorrhea/amenorrhea (OA) in 27 cases and eumenorrhea in 25 were included in this study. Basal serum levels of follicle-stimulating hormone (FSH), luteinzing hormone (LH), estradiol-17beta (E2), prolactin (PRL), testosterone (T), androstenedione (A4) dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (OHP), and SHBG were determined, and the area under the curve (AUC) for E2 was plotted. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DEXA). The mean age for eumenorrheic patients was 26 years (range, 17 to 31), and for OA patients, 24 (range, 16 to 29). Both groups had similar Ferriman-Gallwey scores. Basal levels of PRL, LH, FSH, E2, T, A4, OHP, and DHEAS were similar for eumenorrheic and OA patients. The AUC for E2 was significantly higher for eumenorrheic patients, and DEXA at the lumbar spine demonstrated a significant difference between eumenorrheic (1.222 +/- 0.240 g/cm2) and OA (1.016 +/- 0.108 g/cm2) hirsute women (P < .01). In conclusion, OA, due to a relative hypoestrogenism, may be correlated with osteopenia in young hirsute women.

Pregnancy associated osteoporosis: the familial effect.

OBJECTIVE: The etiology and pathogenesis of pregnancy associated osteoporosis is unclear. Whether pregnancy has simply been an aggravating factor or is a direct etiologic cause responsible for severe bone loss needs to be elucidated. METHODS: In order to evaluate the contribution of familial factors to pregnancy osteoporosis, we analyzed the bone mass of 15 relatives of 5 women with pregnancy osteoporosis. Most of the patients suffered from severe back pain associated with vertebral fractures in their first pregnancy. Extensive clinical, laboratory and radiological investigations were performed to exclude secondary causes of osteoporosis. Bone mineral density measurements were performed on 15 first order family members and the results were compared with those of a control group of 20 healthy members of 5 families. RESULTS: Osteoporosis was present in 53% of the relatives of patients with pregnancy osteoporosis and in 15% of the controls (P < 0.05). CONCLUSION: These results highly suggest that some patients with pregnancy associated osteoporosis have a genetic determination of low peak bone mass, and gestation, due to its association with physiological metabolic disturbances, constitutes a risk factor for the development of skeletal fractures in these patients.

Antagonism of oestrogen-induced prolactin release by medroxyprogesterone acetate.

Previous studies conducted at our clinic suggested that the administration of hormone replacement therapy (HRT) in postmenopausal women could result in the inhibition of oestrogen-induced prolactin (PRL) release. The aim of this study was to determine how the pituitary function is affected by the sequential addition of medroxyprogesterone acetate (MPA) to oestrogen replacement therapy. Twenty-one postmenopausal women receiving no other medication were treated with a standard dose (0.625 mg/day) of conjugated equine oestrogens (CEE) for a period of 24 days, plus 5 mg/day MPA added sequentially during the last 12 days of the oestrogen therapy. Blood samples were collected before treatment, during oestrogen and oestrogen-progestogen administration and after cessation of treatment. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-oestradiol (E2) and PRL levels were studied. During treatment gonadotrophin concentrations decreased significantly, while after cessation of HRT the levels of FSH and LH increased. These gonadotrophin fluctuations indicated a sharp rise in E2 levels during therapy and a significant decrease during the treatment-free period. PRL levels were found to be higher during CEE therapy, but they fell when patients received CEE in combination with MPA. These observations suggest that the role of progestogens in a variety of experimental and clinically relevant situations needs to be investigated not only as regards their direct action but also their modulation of the effect of oestrogen.

Effects of oophorectomy and hormone replacement therapy on pituitary-gonadal function.

The purpose of this study was to determine how oophorectomy and different hormone replacement therapy (HRT) regimens using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day) influence the pituitary-gonadal axis function. Ninety (90) women, who had had regular menses prior to surgery, completed a 1-year follow-up period. Patients were assigned to 5 groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms day transdermal oestradiol (E2) cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These 3 groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day of MPA continuously, while the fifth (n = 19) constituted a control group. After oophorectomy all patients showed increases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and decreases in those of E2, oestrone (E1), prolactin (PRL), sex-hormone-binding globulin (SHBG), androstenedione (delta A4) and testosterone (T). No changes were detected in dehydroepiandrosterone sulphate (DHEA-S) levels. After HRT, decreases in FSH, LH and PRL levels and increases in those of E2, E1 and SHBG were observed, but no changes were seen in T, delta A4 or DHEA-S plasma levels. As the differences that were found cannot be attributed to the presence of ovaries, it is reasonable to assume that they were perhaps due to the treatment. All these changes, with the exception of a decrease in PRL levels, are therefore to be expected after HRT.

Facial wrinkling in postmenopausal women. Effects of smoking status and hormone replacement therapy.

BACKGROUND: There is some evidence that hormone replacement therapy may produce significant improvements in fine wrinkling, while aging skin is more frequently found in smokers. However, studies of the combined effect of a protective factor, such as HRT, and a damaging factor, such as smoking, are rare. OBJECTIVES: To determine in postmenopausal women the relationship between smoking status and the average number of packets of cigarettes since the subject took up smoking (packs-years) on the one hand, and facial wrinkling on the other, and to evaluate the role of hormone replacement therapy in the prevention of wrinkles in smokers and non-smokers. METHODS: All subjects were recruited from our menopause clinic at Hospital Clínic i Provincial in Barcelona and were placed into one of three groups according to their smoking status: 215 life-long non-smokers, 306 former smokers and 209 current smokers. Smoking status, pack-years and hormone replacement were assessed by direct questioning. Facial wrinkle scores were estimated by standardized visual assessment. RESULTS: The relative risk of moderate-severe wrinkling for current smokers compared to that for life-long non-smokers was 2.57 (confidence interval: 1.83-3.06; P < 0.0005). Pack-years was positively related to facial wrinkles. Life-long non-smokers receiving HRT had lower facial wrinkle scores than Life-long non-smokers who had never received HRT. HRT did not, in general, modify the facial wrinkle score in current smokers. CONCLUSION: Our results suggest that the risk of facial wrinkles is greater in smokers and that HRT does not diminish this risk.

Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women.

BACKGROUND: The main goals of estrogen replacement therapy (ERT) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life (QL). Androgens and tibolone therapy may increase bone mineral density (BMD) to a greater extent than ERT and offer an increase in QL. Lipid and cardiovascular effects, however, are still a major concern. AIM: To evaluate whether the addition of a weak androgen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy. SUBJECTS AND METHODS: This prospective study enrolled 120 surgical postmenopausal women; of these, 96 completed the 1-year follow-up. Patients were allocated to one of four groups. The first group (A; n = 23) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydroandrosterone im monthly. The second group (E; n = 26) received 50 microg/day of transdermal 17-b-estradiol continuously; the third (T; n = 23) received 2.5 mg of tibolone every day; and finally, the fourth group (C; n = 24) constituted a treatment-free control group. Bone mass (dual X-ray absorptiometry), serum total cholesterol, HDL, LDL, triglycerides, apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up. RESULTS: All active treatment groups showed an increase in BMD. This increase was higher in the A treatment group (4.08% P < 0.01). Sexuality improved significantly with therapy; however, tibolone and androgens increased scores to a greater extent than ERT. Androgen therapy was associated with significant increases in total cholesterol, LDL and triglycerides. Cholesterol and LDL fall into groups E and T, HDL into groups A and T and triglycerides in group T only. CONCLUSION: The combined regimen of androgens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone; its effects on lipids, however, are clearly adverse.

Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid myopathy.

In this report we describe a patient with Sjögren's syndrome (SS) and calcitriol-mediated hypercalcaemia. Initially, there was no clinical evidence of sarcoidosis. The patient had hypercalcaemia associated with increased calcitriol serum levels; circulating interleukin-6 and tumour necrosis factor alpha levels were also elevated. At the beginning, therapy with clodronate was effective in decreasing the serum calcium levels. However, the serum calcitriol decreased only after chloroquine treatment was added. After 2 years of therapy, the patient developed progressive and extensive muscle weakness. A muscle biopsy revealed a very prominent non-caseating granulomatous myopathy. Corticosteroid therapy was then instituted. Although both chloroquine and corticosteroid therapy were associated with decreased serum interleukin and calcitriol levels, only corticosteroid therapy was effective in treating the sarcoid myopathy. The role of cytokines in calcitriol mediated hypercalcaemia is discussed.

The effect of hormone replacement therapy on postmenopausal bone loss.

Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral.