Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy.

BACKGROUND: Women with exercise-associated amenorrhea have a higher frequency of osteoporosis than eumenorrheic runners and sedentary women. The use of hormone replacement therapy was suggested many years ago to increase bone density in exercising women with amenorrhea and low bone density. OBJECTIVE: To determine if hormone replacement therapy increased bone density in women with exercise-associated amenorrhea. METHODS: We performed a retrospective clinical study comparing the changes in bone density in 8 women runners who took hormone replacement therapy with 5 who refused medication but who were followed up as controls over 24 to 30 months. RESULTS: Vertebral and femoral neck bone density significantly increased by 8.0% +/- 1.2% (+/- SEM) and 4.1% +/- 0.3% (+/- SEM), respectively, in 8 women runners with amenorrhea taking 24 to 30 months of estrogen replacement therapy with progestational support. Control women not taking replacement therapy had nonsignificant decreases of less than 2.5% at each site. CONCLUSION: Hormone replacement therapy appears to increase bone density in amenorrheic runners.

Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism.

Recent evidence suggests that the biologically active testosterone includes both the free and albumin-bound fractions, while the sex hormone-binding globulin (SHBG)-bound steroid dissociates less readily. To examine the significance of the non-SHBG-bound testosterone (i.e. free plus albumin bound) in hyperandrogenism, we obtained single blood samples from 17 normal women, 20 regularly menstruating but hirsute women, and 20 oligoamenorrheic hirsute women. Each serum sample was analyzed for total testosterone by RIA, SHBG-binding capacity was determined by protein precipitation with 50% saturated (NH4)2SO4, and albumin was measured by colorimetry. Non-SHBG-bound and free testosterone and the testosterone to SHBG molar ratio were then calculated. Non-SHBG-bound testosterone was also assayed using differential protein precipitation. There were significant differences among the groups in the mean values of all variables (all P less than 0.05) except albumin. Measurement and calculation of serum non-SHBG-bound testosterone produced similar results, suggesting that the binding equation is valid. There was considerable overlap between normal (control mean +/- 2 SD) and abnormal subjects in all variables except non-SHBG-bound testosterone, for which only 3 regularly menstruating and 2 oligoamenorrheic hirsute subjects were in the normal range. As total testosterone levels increased, there was a significant increase in the ratio of non-SHBG-bound testosterone to free testosterone. These data suggest that albumin becomes increasingly more important in testosterone binding as the total serum testosterone level increases and that non-SHBG-bound testosterone may be the optimal marker to identify hyperandrogenism in hirsute women.

Acute suppression of circulating testosterone levels by cortisol in men.

The effect of acute activation of the ACTH-adrenal axis on circulating testosterone (T) levels was investigated. Elevation of circulating cortisol resulting from insulin-induced hypoglycemia or the administration of hydrocortisone was followed by a rapid decrease in serum T levels, without accompanying changes in LH or PRL. These findings suggest that hypercortisolism of endogenous or exogenous sources suppresses T secretion by a direct action on the testis. This adrenal-testicular axis may have biological implications on the reproductive adaptation to stress.

Defects in pulsatile LH release in normally menstruating runners.

Intense physical exercise has been associated with reproductive dysfunction and menstrual cycles may be abnormal in a majority of women with a heavy training load. To determine whether training influenced pulsatile LH release, we measured LH pulse frequency, LH pulse amplitude and area under the curve over six hours during the early follicular phase of the menstrual cycle in four sedentary women and six eumenorrheic women runners with a training volume of at least 32 km per week. All three LH variables were significantly lower in runners than in controls. These data suggest that there is a central inhibition of the hypothalamic-pituitary-gonadal axis in eumenorrheic runners.

Endurance training decreases serum testosterone levels in men without change in luteinizing hormone pulsatile release.

Cross-sectional studies have suggested that total and bioavailable testosterone levels are reduced in some male athletes. Such changes may be related to loss of body weight, increased serum cortisol, and/or alterations in LH pulsatile release. To determine how endurance training may affect androgen levels, we measured serum total testosterone, sex hormone-binding globulin, free androgen index, LH, FSH, PRL, cortisol, and weight in 15 previously sedentary males. We also examined pulsatile LH release in a subset of 5 subjects. Over 6 months of training, the men increased weekly running mileage to an average of 56 km/week. Total testosterone and free androgen index levels decreased significantly. PRL and cortisol also decreased, while single sample LH and FSH remained unchanged. There was a significant reduction in weight, which did not correlate with changes in serum testosterone levels. LH pulsatile release was not altered by training in the subset of 5 runners. These data confirm previous findings of physiological reduction in serum testosterone and PRL levels and suggest that the testosterone decrease is not related to changes in LH pulsatile release, weight, or increased serum cortisol levels.

Evidence for an influence of the ovary on circulating dehydroepiandrosterone sulfate levels.

Circulating dehydroepiandrosterone sulfate (DS) declines in old age, falling to almost undetectable levels after the seventh decade. Since an accelerated decrease occurs after the menopause, we sought to determine whether ovarian factors may influence adrenal DS secretion independent of chronological age. DS, cortisol, and estradiol levels were compared in subjects grouped according to age, ovarian function, and estrogen replacement. Our data show that premature ovarian failure and ovariectomy in young as well as in postmenopausal subjects precipitate an earlier decline in DS levels. There were no accompanying changes in cortisol levels and no correlations among levels of DS, cortisol, and estradiol. Long term estrogen replacement (over 10 yr) in postmenopausal women over age 65 had no beneficial effect on the age-related DS decline. We suggest that ovarian factors separate from estrogen-mediated effects significantly influence the reduction of DS levels independent of age.

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Recurrent nonimmune hydrops fetalis.

A case of recurrent nonimmune hydrops fetalis is presented. In each of the 2 pregnancies involved, early neonatal death occurred. Only 1 other case could be discovered in the literature where the problem recurred. Hence, normally, a good prognosis for future pregnancies is given. In spite of extensive investigation, the etiology of nonimmune hydrops fetalis remains unknown. The condition is associated with preeclampsia, polyhydramnios, and premature labor. While the polyhydraminos renders management difficult, it makes the ultrasound diagnosis much clearer. This early diagnosis ensures the availability of optimal perinatal care for the infant on delivery.

Urologic and obstetric significance of urinary calculi in pregnancy.

Thirteen patients whose pregnancies were complicated by urinary calculi are presented. Difficulties of diagnosis and treatment with reference to obstetric outcome were assessed. In this series the evidence shows that diagnosis with a high index of suspicion is not difficult. There are apparently no ill effects on the pregnancy from the calculus nor from any necessary surgical management.

Intrauterine testicular torsion: not an emergency.

A case of intrauterine testicular torison and infarction is described. Urgent exploration of the testis has been advocated in the management of this condition. However, the risks of early anesthesia in the immediate postdelivery period must be weighed against the chances of a successful outcome of the operation in preserving testicular function. Since this salvage rate is poor, we suggest surgical exploration at a time when the infant's condition is stable, unless there are indications that the event is very recent.

Lack of consistency in the indirect methods of estimating percent body fat.

Several studies have emphasized the relationship between body composition and the initiation and/or maintenance of cyclic ovarian function in women. A number of methods of indirectly calculating percent body fat have been used, but there is no clear evidence that the various calculations produce consistent results. We therefore compared five different ways of estimating the "percent body fat" in a total of 18 young women, including 6 normal control subjects who did not exercise, 6 regularly menstruating runners, and 6 amenorrheic runners. There was considerable individual variation in the estimates of body fat; and significant differences among groups were found by some, but not all, methods of calculation. It is suggested that because of the inconsistency of estimates, the use of the term "percent body fat" is misleading and that opposite conclusions may result from the use of different methods of calculating body fat in the same groups of individuals.

Factors determining fertility after conservative or radical surgical treatment for ectopic pregnancy.

OBJECTIVE: To examine factors determining choice of radical or conservative surgical procedure for tubal ectopic pregnancy and subsequent pregnancy rates. DESIGN: A retrospective study collating information from the operative notes and previous gynecologic history associated with the choice of procedure and pregnancy rates and outcome over 3 years after a primary tubal ectopic pregnancy. PATIENT(S): Thirty-four women who had undergone conservative (tube sparing) and 56 who had undergone radical (salpingectomy) surgical treatment for tubal ectopic pregnancy at least 3 years before the study. MAIN OUTCOME MEASURE(S): The main outcome measure was the occurrence of a pregnancy (live birth, miscarriage, or ectopic pregnancy) over 3 years after the ectopic pregnancy. RESULT(S): The type of surgery performed was not affected by a previous history of infertility, known pelvic inflammatory disease, the presence of tubal adhesions, or abnormalities on the contralateral tube. Intrauterine pregnancy was not more likely after conservative treatment of ectopic pregnancy but, equally important, the risk of a further ectopic pregnancy was not increased. The single factor that was clearly associated with future fertility problems was a past history of infertility. CONCLUSION(S): Better results may be obtained by careful selection of operative procedure based on history and findings at the time of surgery.

Combined laparoscopy and minilaparotomy in the management of unruptured tubal pregnancy: a preliminary report.

Following laparoscopic diagnosis of unruptured tubal pregnancy, six patients underwent partial salpingectomy using a minilaprotomy technique. None of the patients had any complications resulting from the surgery. Four were discharged within 48 hours of surgery and the others on the 3rd postoperative day. When an ectopic pregnancy has been diagnosed before rupture the technique seems preferable, as it entails a less extensive hospital stay than does conventional laparotomy. The smaller incision is more comfortable and is cosmetically acceptable. The technique is relatively easy to use, and it is hoped that the minimal invasion of the peritoneal cavity will have a less deleterious effect on future fertility.

Hysteroscopy in 100 patients.

Seventy-five infertile patients and twenty-five in whom displacement of an intrauterine device (IUD) had occurred were examined under general anesthesia. The Storz 4-mm hysteroscope was utilized. In all cases Hyskon, high-molecular weight dextran, was used as the distention medium. Concurrent laparoscopy was performed in 80 patients. The hysteroscopic findings were compared with preoperative salpingograms or pelvic x-radiographs. In the infertility group the technique proved to be of special value in locating intrauterine adhesions which had not been detected radiologically. In the "lost IUD" group, hysteroscopy proved to be superior to radiography in determining whether or not a device was located within the uterine cavity, and greatly facilitated removal. Failure to carry out the procedure occurred in four patients. One suffered a serious complication: anaphylaxis to the dextran. It was concluded that hysteroscopy is a simple procedure carrying little risk. It is superior to hysterosalpingography in detecting intrauterine disease which may be a cause of infertility. It is greatly superior to radiology for the detection of lost IUDs.

Combined laparoscopy and hysteroscopy in the investigation of the ovulatory infertile female.

A previous study had demonstrated the superiority of hysteroscopy over hysterosalpingography for the detection of intrauterine lesions in infertile patients. One hundred and sixty-nine patients were examined by a combined laparoscopic and hysteroscopic technique as the means of detecting tubal, peritubal, peritoneal, or intrauterine causes of infertility. Laparoscopy was successful in 168 and hysteroscopy in 162. The rate of diagnosis by laparoscopy of 49.4% was increased to 66% when the hysteroscopic findings were included. Only one serious complication was recorded, the inadvertent visualization of an intrauterine pregnancy. Arguments are advanced for the replacement of hysterosalpingography with combined laparoscopy and hysteroscopy as the primary means of investigating the ovulatory infertile female.

Psychological well-being and coping patterns in infertile men.

OBJECTIVE: To determine whether differences existed in mood and coping styles among fertile men, oligoasthenospermic men, or euspermic men whose wives were undergoing ovulation stimulation with clomiphene and IUI. DESIGN: A cross-sectional research design. SETTING: Hospital-based academic fertility clinic. PATIENT(S): 30 fertile men with currently pregnant wives, 30 euspermic and 30 oligoasthenospermic men in couples undergoing ovulation stimulation with clomiphene and IUI. INTERVENTION(S): Measures of psychological well-being and coping were administered. MAIN OUTCOME MEASURE(S): Biodemographic information, and psychometric measures of mood and coping. RESULT(S): There were no significant differences among the groups on any of the measures except the Family Inventory of Life Events (FILE), in which fertile men reported higher stress levels. FILE scores in all groups were moderate, indicating typical levels of family stress. CONCLUSION(S): Mood and coping in the three groups were similar. This study suggests that men's psychological adjustment to their own infertility and to unexplained infertility is generally healthy.

Hot flushes during breast feeding?

The initiation of breast-feeding was accompanied by an increase in skin conductance followed by increased skin temperature. The pattern was similar to that observed during a menopausal hot flush and differed from sympathetic arousal and simple heating.

The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels.

Endometrial biopsy specimens were obtained from 107 normally menstruating infertile women 2 to 3 days before the anticipated onset of menses and were day-dated according to histologic criteria. A simultaneous blood sample was obtained for measurement of progesterone (P) and beta-subunit of human chorionic gonadotropin. Of 98 biopsies which could be accurately dated, 56 were in-phase (IP) and 42 were out-of-phase (OOP). Mean serum P levels were significantly lower in women with OOP biopsies undertaken more than 4 days before the onset of menses. A sharp decline in serum P levels was observed in women with IP but not OOP biopsies, so that on the final premenstrual day serum P levels were significantly higher than normal in women with OOP biopsies. Pregnancy continued without interruption in two of six patients who underwent biopsy in the cycle of conception. One patient had an ectopic pregnancy; and the three remaining pregnant patients, all with subnormal P values, aborted. The study suggests that there is a high frequency of minor abnormalities in luteal function in normally menstruating, infertile women for whom tubal and male factors were normal. The frequency of subclinical pregnancy (2 of 107) was lower than anticipated from earlier studies.

Estrogen replacement therapy and female athletes: current issues.

Physicians commonly recommend estrogen replacement as treatment for exercise-associated amenorrhoea. While the evidence shows that the basis of the amenorrhoea is estrogen deficiency, it is not clear that it is the only factor in the development of lowered bone density found in oligo-amenorrhoeic female athletes. Nutritional factors, significant in the development of the reproductive dysfunction, could also contribute to bone loss. No randomised, controlled studies of estrogen replacement in athletes have been published. However, one nonrandomised study of a small group of athletes does suggest that there are significant gains in bone density to be made by the initiation of estrogen therapy. More research is clearly needed.

The effects of exercise on reproductive function in men.

Physical activity has a range of effects on male reproductive function depending upon the intensity and duration of the activity and the fitness of the individual. In general, it appears that relatively short, intense exercise increases serum testosterone levels, but there is debate to what degree haemoconcentration, decreased clearance and/or increased synthesis are involved. It is clear from the promptness of the testosterone increment that the mechanism does not involve gonadotrophin stimulation of the testes. There is suppression of serum testosterone levels during and subsequent to more prolonged exercise (and to some extent in the hours following intense short term exercise). Again the mechanisms are not clear: a variety of systems could influence the decrease of testosterone synthesis, including decreased gonadotrophin, increased cortisol, catecholamine or prolactin levels, or perhaps even an accumulation of metabolic waste materials. Endurance training induces changes in the function of the reproductive axis in men in a manner which appears similar to the changes in women. As in women, there is a subclinical inhibition of normal reproductive function but it is unclear whether clinical expression of reproductive suppression is common in men. The long term, physiological suppression of the hypothalamic-pituitary-gonadal axis in men is probably not of major significance but it is clear that further investigation in several areas is essential to provide continuing reassurance that 'exercise is good for you'.