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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contraceptive efficacy of gossypol was investigated in a double-blind, randomized, control study. 75 male volunteers were placed on a regimen of 20 mg of gossypol per day, while the 77 controls received a placebo. Each of the volunteers continued use of gossypol for at least 14 1/2 months. Of the 64 gossypol-treated participants who completed the study, 31% achieved azoospermia and 61% had a sperm count less than 4 x 10 6. A 92% efficacy rate was achieved at the end of the loading phase. Incidence rates for fatigue, decrease of libido, and appetite did not differ significantly between subjects and controls, nor were there any differences in terms of body weight, hemoglobin, serum potassium, or blood pressure. Efficacy rates of 87%, 97%, 95%, 92%, and 98% were achieved at the end of loading, 3, 6, 9, and 12 months of maintenance, respectively. The only significant side effect appeared to be a lowering of serum potassium levels during the maintenance phase. The attrition rate was 26% at 6 months and 39% at 12 months. There were no pregnancies among the wives of the volunteers. At present, gossypol research in China is aimed at the supplementation of gossypol contraception with potassium salt or with a potassium blocker to ameliorate gossypol-related hypokalemia.
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PMID:Clinical trial of gossypol as a male contraceptive drug. Part I. Efficacy study. 330 87

12 Brazilian men were treated with gossypol for 1 year. The treatment schedule consisted of oral administration of 20 mg gossypol daily for 4 months, followed by a maintenance dose of 20 mg on alternate days (o days/week), totaling 60 mg weekly for 8 months. 10 men became azoospermic at the end of the 4th month of treatment, and the other 2 developed marked oligospermia with necrospermia. Except for 1 man who complained of transient listlessness and fatigue, the subjects reported no side effects during treatment. No changes in libido or potency were reported, and plasma testosterone remained unchanged. Blood chemistry values, which included complete blood cell count, cholesterol, glucose, triglycerides, acid phosphatase, urea, transaminases, sodium, and potassium, were not changed significantly during treatment. The response of the pituitary to gonadotropin-releasing hormone stimulation and the response of the testis to gonadotropin stimulation appeared normal in men treated with gossypol. After treatment, sperm counts reverted to essentially normal levels in 8 of 12 men. In 4 men, azoospermia continued 1 year after gossypol treatment discontinuation. Retrograde phlebography carried out in 3 of 4 men who remained azoospermic after therapy discontinuation revealed subclinical varicocele.
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PMID:Antispermatogenic action of gossypol in men. 646 76

An earlier study conducted by the authors indicated that body potassium levels were partially maintained in male langur monkeys treated with gossypol acetic acid (5 mg) and potassium salt supplementation. The present study sought to confirm the persistence of hypokalemia at two higher dosage levels (7.5 and 10 mg/animal/day) and assess the role of exogenous potassium salt (0.50 and 0.75 mg/animal/day) in preventing gossypol-induced hypokalemia. The two dosages of highly purified gossypol acetic acid were administered alone and in combination with potassium chloride for 180 days. All regimens produced severe oligospermia and azoospermia. However, monkeys who received gossypol alone showed significant potassium deficiency with signs of fatigue at both doses. On the other hand, animals receiving gossypol acetic acid and potassium salt supplementation showed normal serum potassium with a less significant increase in urine potassium level during treatment. Also noted was a gradual but significant elevation in the activity of serum transaminases. All parameters returned to normal 150-180 days after treatment termination. The hypokalemic effect documented in this study with gossypol alone may be due to renal leakage and gastrointestinal disturbances.
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PMID:Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey. 940 7

In recent years, continuous optimization of therapy has decisively improved the prognosis of Hodgkin's disease. However, this improvement in overall survival has also led to an increase in several possible late effects which the clinician must be aware of. Due to the appearance of chronic fatigue symptoms, cardiopulmonary problems, hypothyreosis and damage to the gonadal system including azoospermia and ovarian insufficiency, the mostly young patients often suffer a persistent reduction in quality of life. In addition, the increased incidence of second malignancies following successful primary treatment presents a considerable problem. While complete remission and prolonged survival were previously the main objectives in the therapy of malignant lymphomas, reduction or avoidance of toxicity is now becoming more and more central. This development has led to the increasing importance of late sequelae and quality of life as endpoints in modern therapy trials in oncology.
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PMID:[Long-term toxic sequelae of the treatment of Hodgkin's disease]. 1094 98

Klinefelter's syndrome affects 1 in 500 men across all ethnic groups but the diagnosis is often delayed because of substantial variations in clinical presentation. A 26 year-old male came to observation for chronic fatigue. His laboratory data and radiological examination were negative. Examination showed eunuchoidal body habitus with sparse facial hair, small and firm testes and no gynecomastia. The patient had heterosexual orientation with regular sexual intercourses but diminished libido. Serum gonadotropin concentrations were raised while serum testosterone concentration was low-normal level. Serum PRL concentration and thyroid function were normal. Seminal analysis revealed azoospermia and peripheral lymphocyte karyotyping showed a 47,XXY karyotype, confirming diagnostic suspicion. Patient was given testosterone enanthate 200 mg intramuscularly every 2 weeks. He noted improvements in fatigue and libido and increase of muscle mass. Since the true prevalence of Klinefelter's syndrome is very high, the diagnosis of this disease should be considered in every men with complaints related to hypogonadism (fatigue, weakness, gynecomastia, infertility, erectile dysfunction, small testis and osteoporosis). Testosterone replacement therapy should be started early to minimize the physical and psychological effects of androgen deficiency. There have been recent advances in the options for the treatment of infertility in patients with Klinefelter's syndrome: however findings that this syndrome may be transmitted by the new assisted reproductive techniques is cause for concern.
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PMID:[Klinefelter's syndrome: diagnosis and treatment. Case report]. 1167 82

In the 1974-86 period, gossypol acetate was taken as an antifertility measure by 16 men. The initial dose was 20 mg/day, with a maintenance dose of 40 mg/week. Antifertility efficacy was obtained in all 16 cases. Azoospermia persisted in 1 case where the gossypol had been taken for 8 years and discontinued for the past 2 1/2 years. Symptoms experienced in the first 2 weeks of gossypol acetate administration included dizziness, anorexia, nausea, fatigue, and stomach discomfort. Results of examinations of blood and urine; functions of the heart, liver, lung, and liver; electrolytes; external genitalia; and sexual performance were all in the normal range. Measurements of semen, plasma biochemistry, and endocrine changes also were within normal limits. However, in the 9 cases in which the average value of plasma testosterone was near the lower limit of normal, the average value of follicle-stimulating hormone was higher than normal and the testosterone/luteinizing hormone ratio was unusually low. Testis biopsy indicated that long-term gossypol treatment affected both germ cells and Sertoli cells. Leydig cells also demonstrated some damage. Gossypol acetate is, in general, considered an ideal male contraceptive because of its long-term effectiveness, reversibility, and lack of severe toxic side effects.
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PMID:Antifertility treating with long term gossypol. 1226 55

The serendipitous discovery of gossypol by the Chinese in 1978 may represent the most significant advance ever made in terms of male contraception. Protection from pregnancy has been achieved in 99% of couples who use gossypol. The contraceptive effect seems to be maintainable through a dose of 50 mg/week. Azoospermia can persist for as long as 4 years after gossypol discontinuation. The incidence of overt toxicity in men taking contraceptive doses of gossypol is low, although fatigue, changes in libido, loss of appetite, and headache have been reported. Hypokalemia, the most potentially life-threatening side effect, occurs in an estimated 10% of men who use gossypol for contraception. There is a need for more evaluation of the cardiovascular action of contraceptive doses of gossypol. Animal studies have revealed marked species differences in sensitivity to gossypol's contraceptive action. There is no evidence to date that gossypol has adverse effects on the outcome of subsequent pregnancies or on fetal development, although any drug that interferes with the production and maturation of spermatozoa should be closely monitored from the perspective of reproductive toxicity. It is unlikely that the contraceptive activity of gossypol can be explained by a single molecular event. Development of the contraceptive potential of gossypol is dependent on chemical modifications and the discovery of a derivative with a safe therapeutic ratio. Overall, although gossypol has proven to be an efficient, inexpensive means of fertility control, the side effects of hypokalemia and possibly permanent infertility make it unacceptable at this time.
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PMID:Gossypol: a male contraceptive with potential? 1228 Sep 96

A couple was investigated for subfertility. Haemochromatosis was suspected when the 36-year-old man had failure of ejaculation, fatigue and limited facial hair growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection therapy, levels of ferritin and transferrin decreased and liver enzymes normalized. However luteinizing hormone and follicle stimulating hormone failed to increase to normal levels. Treatment with gonadotropins was then applied, which corrected ejaculation and semen characteristics. His partner failed to become pregnant with ovulation stimulation and intrauterine inseminations. After two unsuccessful IVF procedures she became pregnant in the third procedure. Haemochromatosis should be considered and iron studies performed if subfertility due to an endocrine disorder is being investigated. Deposition in the pituitary or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the patients with C282Y mutation are homozygous (85-90%), but the majority of the carriers will not develop the disease. Deficiency of hepcidin, an important regulator for the iron metabolism, was suspected in our patient, based on the early onset of his disease and the low serum levels of hepcidin. The age at diagnosis and the start of venesections is critical for reversal of organ damage. Aggressive venesection can restore hypothalamic-pituitary-gonadal function, preventing further organ damage. But with increasing disease progression venesection will not restore azoospermia or the failure to ejaculate.
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PMID:[Anejaculation caused by haemosiderosis: male infertility in hereditary haemochromatosis]. 1763 84

An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism) including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG) has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.
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PMID:Preserving fertility in the hypogonadal patient: an update. 2533 50

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.
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PMID:Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG). 2806 4


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