Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women

342 Use of testosterone azoospermia

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from

to prevent

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Journal

cyclophosphamide-induced

Masala A.; Faedda R.; Alagna S.; Satta A.; Chiarelli Rovasio P.P.; Ivaldi R.; Taras MS.; Lai E.; Bartoli E.

G.;

ITA

ANN INTERN MED 1997 126/4 (292-295) BACKGROUND: Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. OBJECTIVE: To study the possible protective effect of testosterone used to inhibit germinal cell activity in men who are receiving cyclophosphamide. DESIGN: Randomized, clinical trial. Setting: University medical center. Patients: 15 patients with the nephrotic syndrome who were treated with cyclophosphamide for 6 to 8 months. Intervention: Five patients received daily oral cyclophosphamide, five received cyclophosphamide in monthly bolus injections, and five received monthly intravenous boluses of cyclophosphamide plus testosterone (100 mg intramuscularly every 15 days). Measurements: Sperm counts, serum folliclestimulating hormone levels, and serum luteinizing hormone levels were measured before, during, and after treatment with cyclophosphamide alone or cyclophosphamide plus testosterone. RESULTS: The 10 patients who did not receive testosterone became azoospermic during cyclophosphamide therapy. In only 1 of the 10 patients did the sperm count return to normal 6 months after discontinuation of therapy. Follicle-stimulating hormone levels were elevated in these patients (mean + SE, 19.20 f 1.28 IU/L in patients receiving oral cyclophosphamide and 16.04 rt 2.22 IU/L in patients receiving intravenous cyclophosphamide alone). All 5 patients who received testosterone became azoospermic or severely oligospermic during treatment but had a normal sperm count 6 months after the discontinuation of therapy. In these patients, the mean sperm count was 45.71 +3.89 x lOsup 6/mL and follicle-stimulating hormone levels were normal (5.08 f 0.56 IU/L). Conclusion: Testosterone given to men before and during an 8-month cycle of cyclophosphamide therapy for the nephrotic syndrome may preserve fertility. Adult-onset idiopathic hypogonadotropic treatable form of male infertility

hypogonadism

-

A

Nachtigall L.B.; Boepple P.A.; Pralong F.P.; Crowley W.F. Jr. USA NEW ENGL J MED 1997 336/6 (410-415) BACKGROUND: Men with isolated gonadotropin-releasing hormone (GnRH) deficiency typically present with an absence of pubertal development. We describe an adult-onset form of idiopathic hypogonadotropic hypogonadism that develops after puberty. METHODS: We studied 10 men (age, 27 to 57 years) with normal sexual maturation, idiopathic infertility, sexual dysfunction,low serum testosterone concentrations, and apulsatile secretion of luteinizing hormone on frequent blood sampling. All the men had otherwise normal anterior pituitary hormone secretion and sellar anatomy. We compared the results of semen analyses and measurements of testicular volume, serum testosterone, inhibin B, and gonadotropins in these men with the results in 24 men with classic GnRH

of Gynecology

& Obstem’cs 57 (1997) 339-348

deficiency before and during GnRH-replacement therapy and in 29 normal men of similar age. RESULTS: Serum gonadotropin concentrations in the men with adult-onset GnRH deficiency were similar before and during pulsatile GnRH administration to those in the men with classic GnRH deficiency. However, as compared with men with classic GnRH deficiency, men with adult-onset hypogonadotropic hypogonadism had larger mean (*SD) testicular volumes (18 * 5 vs. 3 f 2 ml, P < O.OOl>,serum testosterone concentrations (78 f 34 vs. 49 + 20 ng per deciliter [2.7 f 1.2 vs. 1.7 f 0.7 nmol per liter], P = 0.0041, and serum inhibin B concentrations (119 f 52 vs. 60 f 21 pg per milliliter, P < 0.001). Treatment with GnRH reversed the hypogonadism and restored fertility in each of the five men who received long-term therapy. CONCLUSIONS: The recognition of adult-onset hypogonadotropic hypogonadism in men as a distinct disorder expands the spectrum of GnRH deficiency and identifies a treatable form of male infertility.

GYNECOLOGY The mythology

AND ENDOCRINOLOGY

of hormone

replacement

therapy

Hartmann B.W.; Huber J.C. AUT

BR J OBSTET GYNAECOL 1997 104/2 (163-168) OBJECTIVE - To evaluate the literature on contraindications contained in pharmaceutical data sheets of five currently available oestrogen replacement preparations (HRT). These contraindications include cardiovascular disease, diabetes, liver melanoma and diseases, otosclerosis, endometriosis, hormone-dependent turnours. DESIGN - Systematic review. Interventions Oestrogen replacement regimens. RESULTS The contraindications to the five HRT preparations have been taken uncritically from the data sheets of oral contraceptives. In some of these conditions not only is HRT not contraindicated, it is indicated. The data sheets for the HRT preparations all state that cardiovascular disease is a contraindication, but systematic review shows that ischemic heart disease, hypertension and hyperlipidaemia are not contraindications, and in ischemic heart disease HRT may actually be indicated. Similarly, systematic review shows that diabetes, chronic liver disease, endometriosis, some cases of treated cancer of the endometrium and breast, melanoma and otosclerosis are not contraindications to HRT. CONCLUSIONS - The information in the pharmaceutical data sheets of HRT regimens should be modified as more accurate information could influence how these preparations are prescribed by doctors as well as affect patient compliance. Effects of hormone-replacement postmenopausal women

therapy

on fibrinolysis

in

Kwang Kon Koh; Mincemoyer R.; Bui M.N.; Csako G.; Pucino F.; Guetta V.; Waclawiw M.; Cannon III R.O. USA

NEW ENGL J MED 1997 336/10 (683-690) BACKGROUND: Plasma levels of plasminogen-activator inhibitor type 1 (PA&l), an essential inhibitor of fibrinolysis in

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from

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Journal

humans, increase in women after menopause, and this may contribute to the risk of cardiovascular disease. We studied the effects of hormone-replacement therapy on PAI- levels. METHODS: In a randomized, crossover study, we investigated the effects of oral conjugated estrogen (0.625 mg per day) in 30 postmenopausal women and transdermal estradiol (0.1 mg per day) in 20 postmenopausal women, either alone or in combination with medroxyprogesterone acetate (2.5 mg daily) for one month, on plasma PAI- antigen levels. Degradation products of cross-linked fibrin (D-dimer) were measured in serum as an index of fibrinolysis. RESULTS: PAl-1 levels were inversely associated with D-dimer levels at base line (r = - 0.540, P = 0.002). Conjugated estrogen, both alone and in combination with medroxyprogesterone acetate, reduced mean ( + SD) plasma levels of PAI- from 32 + 34 ng per milliliter to 14 f 10 ng per milliliter (P < 0.001) and from 31 t 29 ng per milliliter to 15 &- 11 ng per milliliter (P = 0.0031, respectively; there was a significant inverse correlation between pretreatment PAI- levels and the degree of reduction in these levels during therapy (r = -0.631, P < 0.001 for conjugated estrogen; r = - 0.507, P = 0.004 for combined therapy). The degree of reduction in PAl-1 levels was associated with increases in D-dimer levels both when conjugated estrogen was given alone (r = -0.572, P = 0.001) and when combined hormone therapy was given (r = - 0.541, P = 0.002). Transdermal estradiol caused no significant changes in PAIlevels from base-line values. CONCLUSIONS: Conjugated estrogen, alone or combined with progestin therapy, reduced PAI- levels by approximately 50 percent in postmenopausal women and was associated with enhanced systemic librinolysis. These findings may partly explain the protective effect oi hormone-replacement therapy with respect to coronary artery disease. Estrogen replacement to lipid and lipoprotein

therapy and coagulation: changes

Relationship

Kessler CM.; Szymanski L.M.; Shamsipour Z.; Muesing R.A.; Miller V.T.; Larosa J.C. USA

OBSTET GYNECOL 1997 89/3 (326-331) OBJECTIVE: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. METHODS: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40~60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. RESULTS: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = 0.006) and activity (P = 0.001) and total protein S (P = 0.003) and a significant increase in protein C antigen (P = 0.017). C4b-binding protein also decreased significantly from baseline to 3 months (P < 0.001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = 0.213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes

of Gynecology

(e Obstetrics

57 (1997) 339-348

343

in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = 0.52, P I 0.005; r = 0.38, P 5 0.05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = 0.54, P I 0.005). Triglyceride changes correlated directly with changes in protein C antigen (r = 0.36, P 5 0.05) and activity (r = 0.49, P 5 0.005) and inversely with C4b-binding protein (r = - .58, P I 0.01). Apoprotein B was correlated with free protein S (r = 0.48, P 2 0.01). CONCLUSIONS: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or hy the addition of various progestins. Prevalence replacement

and characteristics therapy in Britain

associated

with use of hormone

Moorhead T.; Hannaford P.; Warskyj M. GBR

BR J OBSTET GYNAECOL 1997 104/3 (290-297) OBJECTIVE: To describe trends in the prevalence of hormone replacement therapy (HRT) use among women living in Britain between 1981 and 1990, and to determine whether women who receive HRT are different from those who do not. DESIGN: Population-based, prospective. observational study. Setting: Fourteen hundred general practices throughout the United Kingdom contributing data to the Oral Contraception Study of the Royal College of General Practitioners (RCGP). Population: Prevalence of use: women still under general practitioner observation in the Oral Contraception Study at the end of December 1981 (n = 19,949), 1984 (n = 18,037). 1987 (n = 16,063), 1990 (n = 13,379). Characteristics of users: 3806 HRT users and 3806 never-users matched for age, hysterectomy status and duration of observation in the Oral Contraception Study. Main outcome measure: Ever-use of hormone replacement therapy. RESULTS: Between 1981 and 1990 there was a threefold increase in HRT use among women both among those who had and those who had not had a hysterectomy. Increasing trends were apparent in all age groups. By December 1990, 19% of all women (36% of those who had had a hysterectomy and 16% of those who had not had a hysterectomy) had ever used HRT; 9% were classified as current users. Forty-one percent of women using HRT who had had a hysterectomy received combined (oestrogen and progestogen) preparations; 31% of those who had not had a hysterectomy received at least one prescription for unopposed oestrogen. Among those who had had a hysterectomy, HRT was more likely to he prescribed in women with a history of smoking, nonpsychotic psychiatric illness, hot hushes, other menopausal symptoms, oophorectomy, migraine or headache. Women with breast cancer were less likely to receive HRT. In women who had not had a hysterectomy, smoking, nonpsychotic psychiatric illness, hot flushes, other menopausal symptoms, migraine, headache and previous use of oral contraceptives increased the chances of HRT being used: a history of breast cancer, ischemic heart disease or- diabetes mellitus