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1.
Gynecol Endocrinol ; 17(4): 329-32, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14503978

ABSTRACT

Recent studies have shown that statins might be potent inhibitors of bone resorption and osteoclast number, and there is evidence for their bone anabolic effects. Statin treatment seems to protect against non-pathological fractures in older women. However, contradictory findings have been obtained. In this retrospective study we found that postmenopausal women on statins and hormone replacement therapy (HRT) showed higher bone mineral density than women on HRT alone. This evidence provides further confirmation of the effect of statins on bone turnover and shows that the combination of HRT and statins reduces the risk of bone fracture by virtue of the antiresorptive effect of HRT and the anabolic and antiresorptive effects of statins.


Subject(s)
Bone Density/drug effects , Estrogen Replacement Therapy , Osteoporosis, Postmenopausal/prevention & control , Pravastatin/pharmacology , Simvastatin/pharmacology , Absorptiometry, Photon , Bone Remodeling/drug effects , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Middle Aged , Retrospective Studies
2.
Maturitas ; 39(2): 185-8, 2001 Aug 25.
Article in English | MEDLINE | ID: mdl-11514117

ABSTRACT

OBJECTIVE: to evaluate the efficacy of combining kava extract with hormone replacement therapy in the treatment of menopausal anxiety. MATERIALS AND METHODS: HAMA score was evaluated before and after therapy in four groups of women in menopause (duration of menopause ranged from 1 to 12 years). The groups were treated with hormone replacement therapy (with and without progestogens) and kava extract or placebo for 6 months. RESULTS: A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. DISCUSSION: The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease.


Subject(s)
Anxiety/prevention & control , Hormone Replacement Therapy , Kava/therapeutic use , Menopause , Phytotherapy , Plants, Medicinal , Female , Humans , Middle Aged , Plant Extracts/therapeutic use , Treatment Outcome
3.
Am J Obstet Gynecol ; 184(3): 350-3, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11228485

ABSTRACT

OBJECTIVE(S): Raloxifene, a selective estrogen receptor modulator, has beneficial estrogen agonist effects on bone and cardiovascular risk factors and estrogen antagonist effects on the breast and uterus. Limited clinical data have shown a sustained decrease in total cholesterol, low-density lipoprotein cholesterol, and homocysteine levels; an elevated homocysteine level is an independent risk factor for atherosclerosis. All of these studies were conducted in relatively young populations of women (mean age, 52-54 years). Raloxifene does not affect hot flushes, a major immediate symptom of menopause. This drug may therefore be useful in older women to prevent osteoporosis and cardiovascular disease. The aim of this clinical study was to evaluate the effects of raloxifene on plasma lipids and homocysteine in older women. STUDY DESIGN: The subjects were 45 healthy postmenopausal women, aged 60 to 70 years. The women were randomly assigned to therapy with raloxifene or placebo, 60 mg/d for 1 year. Twenty-six women received raloxifene and 19 received placebo. Checkups were performed every 3 months. At baseline and after 3, 6, 9, and 12 months of treatment we measured homocysteine, total serum cholesterol, triglycerides, and both high-density lipoprotein and low-density lipoprotein cholesterol. RESULTS: An effect on lipids was evident by 3 months with no significant additional modification at 12 months. Mean low-density lipoprotein cholesterol levels were lowered by 15% and total cholesterol was lowered by 8.5%. No reduction in high-density lipoprotein cholesterol or triglycerides was observed. After 3 months of therapy, homocysteine was significantly lower than at baseline (9.9 +/- 1.6 vs 11 +/- 2.1 micromol/L; P < .05). The greatest reduction with respect to baseline was reached after 6 months of therapy (-19.5% +/- 3%; P < .05). CONCLUSION(S): The results of our study show that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density lipoprotein cholesterol and total cholesterol in healthy older women. Our study shows that in older women raloxifene leads to a 19.5% +/- 3% reduction in fasting homocysteine levels. Raloxifene may have a favorable effect on the incidence of cardiovascular disease in older women.


Subject(s)
Homocysteine/blood , Lipids/blood , Raloxifene Hydrochloride/pharmacology , Selective Estrogen Receptor Modulators/pharmacology , Aged , Calcium Carbonate/administration & dosage , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Chromatography, High Pressure Liquid , Endometrium/diagnostic imaging , Female , Humans , Middle Aged , Patient Compliance , Postmenopause/blood , Postmenopause/drug effects , Triglycerides/blood , Ultrasonography
4.
Gynecol Endocrinol ; 15(6): 466-71, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11826771

ABSTRACT

In the present study we evaluated plasma levels of two markers of bone turnover (osteocalcin (OC) and urinary pyridinium cross-links) in association with bone mineral density (BMI) in different groups of climacteric women. We have investigated 158 women in pre-, peri- and postmenopause. Blood and urine samples for assay of hormones and markers were collected and bone mineral density (BMD) was measured by DEXA densitometry in the distal tenth of the non-dominant forearm. There was a significant increase in mean absolute levels of both markers in perimenopause and women in natural and surgical menopause, with respect to women in premenopause. There was a significant correlation between OC and deoxypyridoline (DPYR) in peri- and postmenopause groups. In peri- and postmenopause groups, BMD was correlated with an increase in the biochemical markers of bone remodeling. In the present study, OC and DPYR were found to have good sensitivity for identifying perimenopausal women with pathological BMD. The present results reveal a positive and significant correlation between DPYR and OC, inversely proportional to BMD, during hormone replacement therapy. These markers therefore turn out to be sensitive not only for monitoring severe pathology of bone turnover, but also for monitoring slight physiological deficits in bone equilibrium beginning in perimenopause.


Subject(s)
Biomarkers/analysis , Bone Density , Bone Remodeling , Menopause , Adult , Amino Acids/urine , Estradiol/blood , Estrogen Replacement Therapy , Female , Humans , Middle Aged , Osteocalcin/blood , Postmenopause , Premenopause , Regression Analysis , Time Factors
5.
Minerva Ginecol ; 52(6): 263-7, 2000 Jun.
Article in Italian | MEDLINE | ID: mdl-11085051

ABSTRACT

BACKGROUND: Anxiety is one of the main symptoms in menopause. The aim of this study was to evaluate the efficacy of the association of Kava-Kava extracts with hormone replacement therapy (HRT) and to compare it with HRT alone in the treatment of postmenopausal anxiety. METHODS: Forty women in physiological or surgical menopause for the past 1 to 12 years were enrolled in the study. Patients in physiological menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day with progestin and Kava-Kava extract at a dose of 100 mg (HRT + K, no. = 13); TTS natural estrogens 50 micrograms/day with progestin and a placebo product (HRT, no. = 9). Patients in surgical menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day and Kava-Kava extract at a dose of 100 mg (ERT + K, no. = 11); TTS natural estrogens 50 micrograms/day and a placebo product (ERT, no. = 7). Each treatment cycle lasted for 6 months. The outcome of the study was to evaluate changes in the HAMA score. RESULTS: A significant reduction in the HAMA score was observed after 3 and 6 months' treatment in all four groups of women studied. The groups treated with the therapeutic association (HRT + K, ERT + K) showed a greater reduction in the HAMA score compared to patients in the groups treated with hormones alone. CONCLUSIONS: The results of this study show that the association of HRT and Kava-Kava extract may represent an excellent therapeutic tool for the treatment of women in stabilized menopause, in particular those suffering from anxiety and depression, given that Kava-Kava therapy accelerates the resolution of psychological symptoms without diminishing the therapeutic action of estrogens on organic disease, such as osteoporosis and cardiovascular disease.


Subject(s)
Anxiety/drug therapy , Hormone Replacement Therapy , Kava/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Plants, Medicinal , Postmenopause , Drug Therapy, Combination , Female , Humans , Middle Aged
6.
Calcif Tissue Int ; 66(4): 263-7, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10742442

ABSTRACT

Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51+/-8 years (43-62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (<1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy.


Subject(s)
Bone Density , Bone Remodeling/drug effects , Calcitonin/therapeutic use , Estrogen Replacement Therapy , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis/diagnosis , Absorptiometry, Photon , Adult , Biomarkers/blood , Bone Density/drug effects , Calcitonin/blood , Cross-Sectional Studies , Female , Humans , Middle Aged , Osteocalcin/blood , Osteoporosis/blood , Osteoporosis/prevention & control , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/prevention & control , Parathyroid Hormone/blood , Procollagen/blood , Retrospective Studies
7.
Eur J Obstet Gynecol Reprod Biol ; 90(1): 103-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10767520

ABSTRACT

OBJECTIVE: To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. SETTING: Gynecological Endocrinology Research Center, University of Siena (Italy). PATIENTS: 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. DESIGN: Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. MAIN OUTCOME MEASURES: Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. RESULTS: Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. CONCLUSIONS: Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.


Subject(s)
Amenorrhea/drug therapy , Clomiphene/pharmacology , Hypothalamus/drug effects , Ovary/drug effects , Pituitary Gland/drug effects , Thyroxine/pharmacology , Adult , Case-Control Studies , Estrogen Antagonists/pharmacology , Female , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/pharmacology , Gonadotropin-Releasing Hormone/pharmacology , Hormones/blood , Humans , Hypothalamus/physiology , Luteinizing Hormone/blood , Luteinizing Hormone/pharmacology , Ovary/physiology , Ovulation Induction , Pituitary Gland/physiology , Reference Values
8.
Horm Res ; 51(2): 85-90, 1999.
Article in English | MEDLINE | ID: mdl-10352398

ABSTRACT

The hypothesis that glucocorticoids have a direct central inhibitory effect on the reproductive axis is sutained by the identification of glucocorticoid receptors on GnRH-secreting neurons and gonadotropic pituitary cells. It has been proposed that glucocorticoids and opioids interact centrally in the regulation of the GnRH-LH axis. The inhibitory effect of glucocorticoids may manifest not only directly through the hormone-receptor link, but also indirectly through an increase in opioid tone. The aim of this study was to evaluate the role of glucocorticoids and glucocorticoids combined with an opioid antagonist, in the regulation of basal and GnRH- and TRH-stimulated secretion of LH, FSH and Prl in 7 women with normal menstrual cycles. Blood samples were obtained every 10 min for an hour. GnRH (50 microgram) and TRH (200 microgram) were administered and blood sampling was continued every 15 min for 2 h (day 1). At 5 a.m. the next day, naltrexone (50 mg) was given and at 8 a.m. the GnRH-TRH test was repeated (day 2). At 5 a.m. on day 3, the patients took 2 mg oral dexamethasone and the test was repeated. At 5 a.m. on day 4, the patients took naltrexone and dexamethasone and at 8 a.m. the GnRH-TRH test was repeated. Administration of naltrexone did not cause significant changes in basal concentrations of LH and FSH and their response to GnRH. The area under the curve of the LH response to GnRH on day 3 was significantly less than on days 1, 2 and 4. Administration of naltrexone (day 2) did not cause any significant increase in basal and TRH-stimulated levels of Prl with respect to day 1. On day 3, dexamethasone caused a reduced response of Prl to TRH. Pretreatment with naltrexone (day 4) prevented this reduction. These results suggest that suppression of the response of LH to GnRH induced by dexamethasone may be partly mediated by endogenous opioids. Dexamethasone led to a reduction in the response of Prl to TRH, and naltrexone blocked this suppression. Hence the suppression of Prl and LH by dexamethasone must be partly mediated by endogenous opioids, which must therefore inhibit pituitary secretion of Prl.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Gonadotropin-Releasing Hormone/pharmacology , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Pituitary Gland/drug effects , Thyrotropin-Releasing Hormone/pharmacology , Adult , Area Under Curve , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Prolactin/blood
9.
Maturitas ; 31(2): 171-7, 1999 Jan 04.
Article in English | MEDLINE | ID: mdl-10227012

ABSTRACT

OBJECTIVES: Here we report the results of a study in which natural estrogens were given transdermally cyclically and continuously for 1 year, and a progestin of the latest generation, namely nomegestrol acetate, was given for 10 days every month and for 15 days every 2 months. METHODS: The patients were a group of 34 post-menopausal women (51-56 years), 18 of whom (group A) were treated with continuous transdermal estradiol (50 micrograms/day) and cyclic oral nomegestrol at a dose of 5 mg/day for 15 days every 2 months for 1 year. The other 16 women (group B) were treated with cyclic transdermal estradiol for 3 weeks with oral nomegestrol for 10 days (12-21)/month. Endometrial thickness was evaluated by transvaginal ultrasonography before and after treatment. At the end of treatment, an endometrial biopsy was performed. Serum total cholesterol, HDL, LDL and triglycerides were assessed at baseline and every 4 months. The characteristics of the cycle were deduced from the diary cards recorded by the women. RESULTS: No significant differences were found in the mean interval between the last dose of nomegestrol and the start of bleeding or in the duration of bleeding. The total number of days of bleeding per year was significantly lower in group A than group B (27 +/- 12 vs. 52 +/- 18; P < 0.01). Total serum cholesterol and LDL significantly decreased after 1 year of treatment in both groups, HDL-cholesterol and triglycerides were found increased at most of the time points studied. CONCLUSIONS: The present protocol involving continuous transdermal administration of estrogen combined with oral progestin every 2 months gave good control of the menstrual cycle, did not increase the risk of endometrial pathology and met with good patient compliance.


Subject(s)
Endometrium/drug effects , Estradiol/administration & dosage , Estrogen Replacement Therapy , Megestrol , Norpregnadienes/administration & dosage , Progesterone Congeners/administration & dosage , Administration, Cutaneous , Administration, Oral , Cholesterol/blood , Drug Administration Schedule , Endometrium/diagnostic imaging , Endometrium/pathology , Female , Humans , Middle Aged , Norpregnadienes/pharmacology , Progesterone Congeners/pharmacology , Triglycerides/blood , Ultrasonography , Uterine Hemorrhage/chemically induced
10.
Clin Endocrinol (Oxf) ; 49(1): 85-9, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9797851

ABSTRACT

OBJECTIVE: Flutamide is a non-steroid antiandrogen that specifically blocks the androgen receptor. We have investigated the effect of flutamide treatment on the adrenal androgen response to corticotrophin releasing factor (CRF) in eight patients with polycystic ovary syndrome (PCOS). PATIENTS: Eight women with moderate to severe hirsutism, ranging in age from 19 to 23 years were enrolled in the study. Basal hormonal pattern showed anovulatory cycles, increased concentrations of LH, androstenedione and testosterone and increased LH/ FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. Each received 250 mg of Flutamide twice a day for 6 months. MEASUREMENTS: Before treatment and at the end of the sixth month, women were evaluated for hirsutism score and a CRF test was performed to evaluate ACTH, cortisol and adrenal androgen responses. RESULTS: Androstenedione (delta 4), DHEA-S, 17-hydroxy-progesterone, testosterone and free-testosterone showed significantly reduced responses after six months of flutamide therapy whereas ACTH and cortisol response were similar to those before treatment. Clinical improvement in the degree of hirsutism was observed in all patients. The Ferriman-Gallwey scores decreased from a mean of 22 +/- 2 to 8 +/- 1.5. CONCLUSION: Flutamide induces a significant reduction in adrenal androgen response to the CRF test but not in the response of ACTH and cortisol. The finding that flutamide does not alter the pituitary-adrenal axis shows that flutamide acts by reducing adrenal androgens. These results demonstrate that flutamide is not only effective in the treatment of hirsutism but also reduces adrenal androgen secretion.


Subject(s)
Androgen Antagonists/therapeutic use , Androgens/metabolism , Corticotropin-Releasing Hormone , Flutamide/therapeutic use , Pituitary-Adrenal System/metabolism , Polycystic Ovary Syndrome/drug therapy , 17-alpha-Hydroxyprogesterone/blood , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/metabolism , Adult , Androgens/blood , Androstenedione/blood , Androstenedione/metabolism , Area Under Curve , Dehydroepiandrosterone Sulfate/blood , Female , Humans , Hydrocortisone/blood , Hydrocortisone/metabolism , Pituitary-Adrenal System/drug effects , Polycystic Ovary Syndrome/physiopathology , Testosterone/blood , Testosterone/metabolism
11.
Minerva Ginecol ; 50(5): 207-11, 1998 May.
Article in Italian | MEDLINE | ID: mdl-9677811

ABSTRACT

BACKGROUND: Menopausal symptoms include hot flushes, insomnia, nocturnal sweating, dizziness, headaches and palpitations. These symptoms reflect adaptation of the body to estrogen deprivation which affects various central neurotransmitters. METHODS: In this study, the efficacy has been tested of a plant product based on extracts of the leaves of Salvia officinalis (sage) and Medicago sativa (alfalfa) in the treatment of hot flushes in 30 menopausal women with these symptoms. RESULTS: Hot flushes and night sweating completely disappeared in 20 women: four women showed good improvement and the other six showed a reduction in symptoms. GnRH and TRH tests were performed in 8 women to evaluate TSH and Prl responses before and after 3 months of therapy. The plants product induced a significant increase in Prl and TSH response to TRH. Basal levels of estradiol, LH, FSH, Prl and TSH were unchanged. CONCLUSIONS: The product seams to have a central slight antidopaminergic action without side effects and is an effective agent in the treatment of menopausal symptoms.


Subject(s)
Dizziness/etiology , Headache/etiology , Hyperhidrosis/etiology , Menopause , Phytotherapy , Dizziness/drug therapy , Female , Headache/drug therapy , Humans , Hyperhidrosis/drug therapy , Middle Aged , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/etiology , Treatment Outcome
12.
Gynecol Endocrinol ; 12(3): 191-6, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9675566

ABSTRACT

Maternal thyroid function in pregnancy is influenced by many factors. This study was undertaken to clarify the mechanism of thyroid regulation in the first trimester of normal pregnancy. We performed the thyrotropin-releasing hormone (TRH) test in eight women in the first trimester (week 6-9) of pregnancy and ten normal women in early follicular phase. Basal plasma levels of free triiodothyronine and free thyroxine were within the normal range in both groups, whereas thyroid-stimulating hormone (TSH) was at the lower limit of the normal range in pregnant women. TRH stimulation evoked a TSH response with a peak of 14.1 +/- 1.2 mIU/ml at 30 min. In control subjects TSH increased in response to TRH with a peak of 7.4 +/- 1.1 mIU/ml at 30 min. Statistical analysis with Student's t test revealed significantly higher TSH levels (p < 0.01) in pregnant women. The most striking finding was the enhanced responsiveness of TSH to TRH stimulation while the thyroid hormones, free triiodothyronine (fT3) and free thyroxine (fT4), remained in the normal range. This response was similar to that observed in central hypothyroidism. These results suggest that the reduction in maternal pituitary TSH levels is due to human chorionic gonadotropin (hCG) inhibition of TRH secretion.


Subject(s)
Thyrotropin-Releasing Hormone/pharmacology , Thyrotropin/blood , Thyrotropin/drug effects , Adolescent , Adult , Female , Humans , Pregnancy , Pregnancy Trimester, First , Thyroid Function Tests
13.
Gynecol Endocrinol ; 12(3): 197-201, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9675567

ABSTRACT

A variant of growth hormone (GH) known as human placental growth hormone (hpGH) is found in maternal serum during pregnancy. It is well established that during the second half of normal pregnancy, pituitary GH secretion is suppressed; however, there are no data about maternal GH secretion during the first trimester of pregnancy. The present study reports the response of GH to thyrotropin-releasing hormone (TRH) in eight pregnant women in the trimester of pregnancy (weeks 6-9) who had previously requested voluntary interruption of pregnancy. The TRH test induced a significant paradoxical GH response with a peak of 9.4 +/- 0.5 ng/ml (mean +/- SD) at 30 min and a higher thyroid-stimulating hormone (TSH) response in pregnant women. The increment was observed until 120 min and no response was observed in the control group. These data show the paradoxical response of GH to TRH, a releasing factor to which the hormone does not normally respond. This paradoxical secretion may be due to direct pituitary stimulation and can be explained on the basis of a state of gestational hypothyroidism.


Subject(s)
Growth Hormone/blood , Growth Hormone/drug effects , Thyrotropin-Releasing Hormone/pharmacology , Adolescent , Adult , Female , Humans , Pregnancy , Pregnancy Trimester, First , Thyroid Function Tests
14.
J Clin Endocrinol Metab ; 83(1): 99-102, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9435423

ABSTRACT

Anovulation in women with polycystic ovary syndrome (PCOS) is the direct effect of high local androgen concentrations on the ovary. Antiandrogens are substances that prevent androgens from expressing their activity on target tissues. Flutamide is a nonsteroid antiandrogen that has been found effective in hirsute patients, although its mechanism of action is unclear. Eight girls, ranging in age from 16-19 yr, with moderate to severe hirsutism and menstrual irregularities were enrolled in this study. The basal hormonal pattern showed anovulatory cycles; increased concentrations of LH, androstenedione, and testosterone; and increased LH/FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. All were given 250 mg flutamide twice a day for 6 months. LH, FSH, androstenedione, testosterone, estradiol, and progesterone were evaluated before treatment, every 4 days during the third month of treatment, and on day 24 of the sixth month of treatment. Hirsutism improved, androgen levels dropped, and ovulatory cycles were restored in all subjects. Ultrasonographic examination in follicular phase showed a significant reduction in ovarian volume and ovaries of normal appearance with one dominant follicle. The most important result of the present study was that flutamide restored ovulation in anovulatory PCOS patients. This finding supports the hypothesis that flutamide reduces androgen synthesis through restoration of ovulation, although a direct block of the steroidogenic enzymes of androgen biosynthesis in ovarian thecal cells cannot be excluded.


Subject(s)
Flutamide/therapeutic use , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/drug therapy , Adolescent , Adult , Androgen Antagonists/therapeutic use , Androstenedione/blood , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Progesterone/blood , Sex Hormone-Binding Globulin/analysis , Testosterone/blood , Time Factors
15.
Contraception ; 55(4): 239-43, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9179456

ABSTRACT

The effects of 6 months of combined hormone therapy with transdermal estradiol (0.05 mg/day x 21 days) and different oral progestogens (10 mg/day medroxyprogesterone acetate [MPA] in the last 12 days, 10 mg/day dihydrogesterone in the last 12 days, and 50 mg/day cyproterone in the first 10 days), on menopausal symptoms and hypothalamo pituitary-ovarian function were studied in normal perimenopausal women. The study included 38 perimenopausal women, aged 43-49 years, with regular cycles of 26-32 days in length and menopausal symptoms. Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, and P every week until menstrual bleeding, before and during the first month of therapy. Plasma levels of LH and FSH were suppressed in the first month of therapy while E2 had a mean value of 45 +/- 12 pg/ml. Ultrasound examination and low levels of P indicated a complete block of ovulation and hypothalamo-pituitary-ovarian activity. All women reported the disappearance of vasomotor symptoms and nocturnal sweating. Transdermal estradiol and oral progestogens were well tolerated. This study shows that combined hormone therapy with low doses of transdermal estrogen patches and different oral progestogens reduces menopausal symptoms and also safeguards against unwanted pregnancies in the perimenopausal period.


Subject(s)
Contraception , Estradiol/administration & dosage , Menopause , Progestins/administration & dosage , Administration, Cutaneous , Adult , Climacteric , Cyproterone/administration & dosage , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Medroxyprogesterone Acetate/administration & dosage , Middle Aged , Norprogesterones/administration & dosage , Progesterone/blood
16.
Hum Reprod ; 12(2): 357-60, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9070725

ABSTRACT

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.


Subject(s)
Danazol/administration & dosage , Estrogen Antagonists/administration & dosage , Gonadotropin-Releasing Hormone/administration & dosage , Leiomyoma/drug therapy , Uterine Neoplasms/drug therapy , Adult , Drug Resistance , Female , Gonadotropin-Releasing Hormone/analogs & derivatives , Humans , Middle Aged
17.
Gynecol Endocrinol ; 10(1): 49-53, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8737192

ABSTRACT

The effects of 6 months of hormone replacement therapy by transdermal estradiol patches (0.05 mg/day for 21 days) and oral progestogens (10 mg/day for 10 days) on hypothalamic-pituitary-ovarian function was evaluated in 32 perimenopausal women, aged 42-47 years, with irregular anovulatory cycles and menopausal symptoms. Hormone levels evaluated on the 8th and 24th day of the cycle preceding therapy showed follicle-stimulating hormone (FSH) levels above 15 mIU/ml, estradiol less than 45 pg/ml and progesterone less than 800 pg/ml. During therapy, there was an improvement in menopausal symptoms, a decrease in luteinizing hormone (LH) and FSH levels, an increase in estradiol levels and the transdermal patches were well tolerated. At the end of therapy, 19 women continued to have regular ovulatory cycles with progesterone levels similar to those in luteal phase. FSH and LH concentrations were significantly lower than before therapy. This study shows that hormone replacement therapy not only improves menopausal symptoms but may also restore the hypothalamic-pituitary-ovarian function.


Subject(s)
Dydrogesterone/administration & dosage , Estradiol/administration & dosage , Estrogen Replacement Therapy/methods , Menopause , Ovary/physiology , Pituitary Gland/physiology , Administration, Cutaneous , Adult , Dydrogesterone/adverse effects , Dydrogesterone/therapeutic use , Estradiol/adverse effects , Estradiol/therapeutic use , Estrogen Replacement Therapy/adverse effects , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Menopause/physiology , Middle Aged
18.
Gynecol Endocrinol ; 7(4): 279-83, 1993 Dec.
Article in English | MEDLINE | ID: mdl-8147238

ABSTRACT

Many studies have shown a physiological reduction in thyroid function with age in animals, and less clearly in humans, with an increase in the incidence of age-dependent clinical and subclinical hypothyroidism. Women are more subject to thyroid dysfunction than men. In postmenopausal women the sudden drop in estrogen levels may affect not only pituitary gonadotropins but also other pituitary hormones directly or indirectly involved in reproductive function. The response of thyrotropin to thyrotropin releasing hormone (TRH) has been shown to decrease with age and basal levels of thyrotropin have been found to be reduced in elderly subjects. In the present study we evaluated the response of thyrotropin to TRH before and after ovariectomy in premenopausal women and during estrogen therapy. The response of thyrotropin to TRH after ovariectomy was significantly less than before. Estrogen replacement therapy restored the thyrotropin response to TRH to pre-ovariectomy levels. This significant decrease in the thyrotropin response to TRH observed in surgical postmenopausal women may be explained by lower endogenous estradiol levels.


Subject(s)
Ovariectomy , Premenopause/physiology , Thyrotropin/metabolism , Adult , Aging/physiology , Estradiol/blood , Estrogen Replacement Therapy , Female , Humans , Kinetics , Middle Aged , Thyrotropin-Releasing Hormone
19.
Fertil Steril ; 60(2): 268-71, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8339822

ABSTRACT

OBJECTIVE: To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in premenopausal women before and after ovariectomy and after 1 month of estrogen replacement therapy (ERT). PATIENTS: Ten women 42 to 49 years of age awaiting combined hysterectomy and ovariectomy for a variety of benign gynecological conditions. INTERVENTION: Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, P, and PRL. Stimulation with GH-RH was performed before and 8 to 10 days after ovariectomy, and after a month of ERT. RESULTS: A significant reduction in GH response to GH-RH was observed after ovariectomy. Estrogen replacement therapy restored GH response to presurgical levels. CONCLUSIONS: The results support the role of E2 in the stimulated secretion of GH and suggest that ERT increases pituitary stores of GH.


Subject(s)
Estrogen Replacement Therapy , Growth Hormone/metabolism , Menopause , Ovariectomy , Adult , Estradiol/blood , Female , Growth Hormone-Releasing Hormone/pharmacology , Humans , Middle Aged
20.
Gynecol Obstet Invest ; 33(1): 31-5, 1992.
Article in English | MEDLINE | ID: mdl-1563655

ABSTRACT

The postpartum period is characterized by high levels of circulating steroids which condition hypothalamo-pituitary activities. In pregnancy growth hormone (GH) levels are greatly increased and lack pulsatility. In order to investigate the behavior of GH during the postpartum period, the GH response to GH-releasing hormone stimulation (50 and 100 micrograms), to amphetamine, a dopamine receptor agonist, and to FK 33-824, an opiate receptor agonist, was investigated in women during the first 5 days after delivery. In all groups GH responses were significantly lower (p less than 0.01) than in normal women studied during the early follicular phase. FK-33-824-induced GH release was similar in postpartum and control women. These results demonstrate reduced pituitary GH response to GH-releasing hormone and to amphetamine in women during the postpartum period, confirming the peculiarity of the hypothalamopituitary component.


Subject(s)
Amphetamine/pharmacology , D-Ala(2),MePhe(4),Met(0)-ol-enkephalin/pharmacology , Growth Hormone-Releasing Hormone/physiology , Growth Hormone/metabolism , Pituitary Gland, Anterior/metabolism , Postpartum Period/physiology , Adult , Amphetamine/administration & dosage , D-Ala(2),MePhe(4),Met(0)-ol-enkephalin/administration & dosage , Dose-Response Relationship, Drug , Female , Growth Hormone/blood , Growth Hormone-Releasing Hormone/administration & dosage , Growth Hormone-Releasing Hormone/pharmacology , Hormones/administration & dosage , Hormones/pharmacology , Humans , Pituitary Gland, Anterior/drug effects , Postpartum Period/blood , Stimulation, Chemical
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