Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study.

OBJECTIVE: To confirm the safety and efficacy of 75 IU lutropin alfa with concomitant follitropin alfa in inducing follicular development in women with profound gonadotrophin deficiency. DESIGN: Double-blind, randomized, placebo-controlled trial conducted in 25 medical centres in four countries. PATIENTS: Thirty-nine patients with LH < 1.2 IU/l and FSH < 5.0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa. MEASUREMENTS: Primary efficacy end-point (intent-to-treat): follicular development defined by (i) at least one follicle >or= 17 mm; (ii) serum E(2) level >or= 400 pmol/l on day of hCG administration (DhCG); and (iii) mid-luteal phase progesterone level >or= 25 nmol/l. RESULTS: In the analysis of evaluable patients, 66.7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20.0% (2 of 10) of patients receiving placebo (P = 0.023). In the intent-to-treat analysis, follicular development was achieved in 65.4% (17 of 26) of patients receiving lutropin alfa and 15.4% (2 of 13) of patients receiving placebo (P = 0.006). The statistical difference between treatment groups was preserved when over-response leading to cycle cancellation was analysed as a failed response (P = 0.034). Lutropin alfa was well tolerated. CONCLUSION: Subcutaneous co-administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency.

Does the addition of salpingectomy or fimbriectomy to hysterectomy in premenopausal patients compromise ovarian reserve? A prospective study.

OBJECTIVE: To evaluate changes in ovarian reserve in patients following hysterectomy, with or without bilateral salpingectomy or fimbriectomy. STUDY DESIGN: Open-label, prospective cohort trial of patients undergoing hysterectomy for benign uterine indications. Levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and ultrasonic measures of peak systolic flow velocity/diastolic velocity (S/D) ratio and resistance index (RI) in the ovarian artery were taken from patients before and 6 weeks after hysterectomy, hysterectomy+salpingectomy or hysterectomy+fimbriectomy. RESULTS: The study period was from November 2011 to May 2014. Sixty patients were included in the final analysis, after two patients were lost to follow-up and one patient underwent bilateral oophorectomy. Of these 60 patients, 16 underwent hysterectomy alone (control group), and 44 were included in the study group (22 patients underwent hysterectomy+fimbriectomy and 22 patients underwent hysterectomy+salpingectomy). The mean age of patients was 46 years (standard deviation 4.07 years). Between-group dfferences in FSH, AMH, ovarian volume, ovarian artery S/D ratio and ovarian artery RI were not significant. CONCLUSION: The addition of salpingectomy or fimbriectomy to routine hysterectomy in premenopausal patients does not diminish ovarian reserve.

Management of labor with umbilical cord prolapse: a 5-year study.

Fifty-one cases of cord prolapse, in which delivery was not imminent and the fetus was still alive, were managed by filling the bladder with 500-700 mL of saline and by intravenous ritodrine. Delivery was by cesarean section as soon as possible. Among the cases so managed, there were no perinatal deaths. The mean 5-minute Apgar score was 9.5, and in only three cases was it less than 7. In eight cases, fetal distress continued after treatment, as compared with 33 cases before this type of treatment started (P less than .001); no difference was found in the outcome between neonates weighing less than or greater than 2500 g.

Nifedipine in the treatment of severe preeclampsia.

We conducted a randomized clinical trial in which patients with severe preeclampsia between 26-36 weeks of gestation received either nifedipine (10-30 mg sublingually, then 40-120 mg/day orally; N = 24) or hydralazine (6.25-12.5 mg intravenously, then 80-120 mg/day orally; N = 25). Effective control of blood pressure was achieved with nifedipine in 95.8% of subjects and with hydralazine in 68%, a statistically significant difference (P less than .05). Maternal side effects were minor in both groups. Acute fetal distress developed in one nifedipine subject and in 11 treated with hydralazine. Mean prolongation of gestation was 15.5 +/- 10 days with nifedipine and 9.5 +/- 11 days with hydralazine, a difference that did not reach statistical significance (P less than .07). Infants born to women treated with nifedipine were delivered at more advanced gestational ages (34.6 +/- 2.3 versus 33.6 +/- 2.4 weeks; statistically not significant), weighed more (1826 +/- 456 versus 1580 +/- 499 g; statistically not significant), and tended to have fewer, mainly minor, complications. The average number of days spent in the neonatal intensive care unit was significantly lower in the nifedipine group (15.1 versus 32.7 days; P less than .005), leading to an average 31% reduction in total (maternal and neonatal) hospitalization-related charges for each nifedipine-treated pregnancy. We conclude that nifedipine is an effective, convenient, and low-cost treatment for patients with severe preeclampsia, and is not associated with undesirable side effects.

Ovarian stimulation and in vitro fertilization in women with mature cystic teratomas.

OBJECTIVE: To report the results of ovulation induction and in vitro fertilization-embryo transfer (IVF-ET) in patients with ovarian cystic teratomas. METHODS: Six women with ultrasonographically diagnosed ovarian cystic teratomas (mean diameter 2.4 cm) who presented with infertility underwent IVF-ET (n = 4) or ovulation induction (n = 2). Serial ultrasound examinations were used to determine the size of the cystic teratomas during therapy and throughout pregnancy. RESULTS: Ovarian stimulation was successful, as evidenced by the serum estradiol concentration on the day of hCG administration (mean in IVF-ET patients, 3558+/-1319 pg/mL) and the number of oocytes retrieved (10+/-4.24). Three patients having IVF-ET and both patients having ovulation induction conceived, and six healthy infants were born. Cyst sizes remained unchanged throughout treatment and pregnancy. There were no cyst-related complications during ovulation induction or IVF-ET, or during the entire course of pregnancy, labor, and delivery. CONCLUSION: The presence of ovarian cystic teratoma should not be considered a contraindication for therapy in women undergoing ovulation induction and IVF-ET.

Vaginal delivery of the second twin in breech presentation.

The obstetric performance of 39 vertex-breech twin-pairs was compared with that of 48 vertex-vertex pairs. No difference was found between the two groups in maternal age, parity, gestational age, birth weight, and Apgar scores. The second twin in breech presentation had a higher incidence of very low birth-weight (less than 1500 g), but of borderline significance (P = .05), and a significantly (P less than .03) longer hospitalization period. The cesarean section rate was 7.7 and 10.4% for the breech and vertex second twin, respectively. In our view, breech presentation of the second twin is not an indication for cesarean section.

Epidemiology, etiology, and fertility drugs in ovarian epithelial carcinoma: where are we today?

OBJECTIVE: To review studies that have examined the epidemiology and etiology of the development of epithelial carcinoma of the ovary. DATA IDENTIFICATION: Important published studies related to the topic were identified through a computerized bibliography search. CONCLUSION: A review of the literature reveals that the etiology of epithelial ovarian cancer is probably multifactorial and that genetic, environmental, hormonal, and viral factors appear to be directly or indirectly related to the development of the disease. An attempt to implicate specific agents has not produced conclusive results. However, based on large epidemiologic studies, it seems that there is a clear trend of decreasing risk with increasing number of pregnancies, deliveries, use of oral contraceptives, and the duration of breast feeding. An increased risk was found to be associated with ovarian dysfunction leading to infertility and exposure to asbestos and talc. The recent observation that infertile women who used fertility drugs might experience an increased risk for the development of epithelial ovarian cancer should be examined very carefully because of the small number of patients in the study, lack of appropriate information about the type of infertility, drugs used, dosage, and duration of treatment. Because there are no screening tests that are consistently accurate enough to detect ovarian cancer at an early stage, translating the current information into disease prevention requires careful clinical evaluation with a routine follow-up of patients at risk.

Amenorrhea during the reproductive years--is it safe?

OBJECTIVE: To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal therapeutic strategy to treat these conditions. DATA IDENTIFICATION: Studies related to these topics were identified through literature and Medline searches. STUDY SELECTION: Those studies that relate specifically to amenorrhea in women of reproductive age, including etiology, diagnosis, and the implications of replacement therapy or nontreatment of this state, were selected. RESULTS: Amenorrhea, as defined by the absence of menses for > or = 6 months, may be found in up to 3% of women in the reproductive years. Classification of amenorrhea involves defining the exact cause for the cessation of menses, be it hypothalamic, pituitary, ovarian, or lower genital tract in origin. The majority of amenorrheic young women have very low levels of estrogens, and a minority will have subnormal noncyclic estrogen levels, unopposed by P, due to anovulation. This distinction is important in considering the long-term implications of amenorrhea. Hypoestrogenic amenorrhea is associated with a significant loss of bone mineral density and the associated risk of osteoporosis and fractures. Lipoprotein profiles are also adversely affected, and this is associated with an increased risk of cardiovascular events. Anovulatory amenorrhea due to "unopposed" estrogen is associated with an increased risk of endometrial hyperplasia and endometrial carcinoma even in young patients. Therapy should be aimed at treating the underlying cause of amenorrhea, if possible, or reconstitution of an estrogen-P biphasic monthly cycle if not. CONCLUSIONS: Untreated amenorrhea is associated with significant long-term morbidity, especially in young women. Early recognition and institution of treatment will minimize late complications.

Estrogen biosynthesis--regulation, action, remote effects, and value of monitoring in ovarian stimulation cycles.

OBJECTIVE: To review current knowledge regarding estrogen biosynthesis, its regulation and action, specifically concerning local as opposed to remote effects of this hormone, and to examine the effectiveness and prognostic value of monitoring hormone concentrations and endometrial response in cycles of controlled ovarian hyperstimulation. DATA IDENTIFICATION AND SELECTION: Studied that relate specifically to estrogen biosynthesis, enzymatic pathways, estrogen receptor physiology, and the clinical aspects of estrogen monitoring were identified through literature and Medline searches. RESULTS: Folliculogenesis is the basic unit of ovarian activity, which has a dual purpose: oocyte maturation and steroid production. Steroidogenic granulosa and theca cells cooperate under gonadotropin control to produced estrogens by stimulating synthesis of steroidogenic enzyme messenger RNAs. Steroid synthesis is amplified further by local growth factors and follicular cell multiplication. Estrogen synthesis is directed by FSH, and only small amounts of LH are needed to amplify the follicular estrogenic potential. However, the growth of preovulatory follicles can proceed without LH, under FSH regulation only, even in the presence of low peripheral estrogen levels. Oocyte maturation and fertilization may proceed independently of ambient estrogen levels, leading to the assumption that estrogen exerts a minimal autocrine-paracrine function. The notable effect of follicular estrogen production is to promote adequate receptive endometrium for embryo implantation. Clinical treatment cycles may be monitored more effectively by evaluating end-organ response to estrogen rather than by evaluating absolute serum E2 concentrations or sonographic follicular measurements. CONCLUSION: Follicular estrogen production is regulated by a complex set of signals that synergize to produce optimal steroidogenesis. Most importantly, the effect of estrogen is truly an endocrine effect, as it prepares the endometrium for implantation. Therefore, the goal of effective treatment and monitoring strategies should focus on direct assessment of the biologic activity of estrogen as it optimizes endometrial receptivity in anticipation of subsequent implantation.

Recombinant technique and gonadotropins production: new era in reproductive medicine.

OBJECTIVE: To review current knowledge regarding recombinant DNA technology and its safety and efficacy in relation to recombinant gonadotropin production. DATA IDENTIFICATION AND SELECTION: Studies that relate specifically to recombinant DNA technology, method of laboratory production, and the clinical aspects of using recombinant gonadotropins were identified through literature and Medline searches. RESULTS: Recent developments in recombinant DNA technology have resulted in a rapidly expanding range of new diagnostic and therapeutic opportunities. This technology paves the way to the identification, isolation, cloning, and production of specific proteins. Recently, recombinant human gonadotropins became available for clinical use. The pharmacokinetics, receptor availability, pharmacodynamics, and safety were studied extensively and the drugs were found to be identical if not superior to urinary gonadotropins that have been used in reproductive medicine for the last 30 years. It is clear today that the use of recombinant human gonadotropins is expected to provide better batch-to-batch consistency, steady supply, and most importantly, a purified compound with high specific activity, which accounts for >99% of the preparation's protein content, allowing SC administration. CONCLUSION: There is no doubt that recombinant gonadotropins produced by genetic engineering technology are here to stay and will represent an important treatment modality in various fertility disturbances.

Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer.

From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration.

CV 205-502--effectiveness, tolerability, and safety over 24-month study.

Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today.

Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone.

OBJECTIVE: An attempt to induce ovulation with a single dominant follicle in polycystic ovarian syndrome (PCOS) patients. DESIGN: Comparing ultrasound and estradiol (E2) measurements during treatment with a low-dose protocol (using purified follicle-stimulating hormone, starting with 75 IU/d and increasing every 7 days by 37.5 IU/d) with those obtained following treatment with a conventional protocol using the same drug. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS PARTICIPANTS: Eight PCOS patients of whom six had failed to respond adequately to the conventional protocol. MAIN OUTCOME MEASURE: Rate of cancellation of cycles, number of leading follicles, and serum E2 concentration at the time of ovulation. RESULTS: Treatment with the low-dose protocol resulted in a significant reduction in the number of leading follicles (P less than 0.04), serum E2 concentrations (P less than 0.0002), and a higher rate of ovulation. As a result, five patients conceived compared with none in the conventional protocol. CONCLUSION: Using the low-dose protocol permitted induction of ovulation safely and successfully in a selected group of PCOS patients who were previously difficult to treat with the conventional ovulation induction protocol.

Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase.

OBJECTIVE: To review studies that have examined the role of LH, its mechanism of action, and its detrimental effects when hypersecreted during the follicular phase. DESIGN: Important published studies related to this topic were identified through a computerized bibliographic search. PATIENTS, PARTICIPANTS: Review of the need for LH during the follicular phase is based on animal models and women with hypogonadotropic hypogonadism. The association of hypersecretion of LH during the follicular phase with low rates of fertilization and high rates of pregnancy loss is based on clinical studies conducted in patients treated by IVF and ET and by induction of ovulation. The possible mechanism by which the effects occur is based on in vitro studies. RESULTS: The results of the studies cited in this review are consistent with the two-cell two-gonadotropin hypothesis implying that synergistic action of both FSH and LH is required for appropriate steroidogenesis. It also seems that, whatever the underlying mechanism, a raised serum LH concentration during the follicular phase confers a substantial risk of infertility and early pregnancy loss. CONCLUSION: By reviewing the literature it appears that LH exhibits an important role in the development of the growing follicle and maturation of the oocyte. It also seems that hypersecretion of LH during the follicular phase implies adverse effects on the fertility process. To further test this hypothesis, we now need systemic assessment of the methods of therapy used for treating patients with polycystic ovary syndrome, in relation to LH secretion and outcome of pregnancy.

Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome.

OBJECTIVE: To characterize the ovarian response in patients with isolated hypogonadotropic hypogonadism with ultrasound (US) findings of polycystic ovaries (PCO). DESIGN: Twenty-seven treatment cycles in patients with hypogonadotropic hypogonadism and US findings of normal ovaries were compared with 31 cycles in patients with hypogonadotropic hypogonadism and US-diagnosed PCO. Forty-one cycles in the hypogonadotropic hypogonadism and US-diagnosed PCO were compared with 59 cycles of patients with polycystic ovarian syndrome (PCOS) to examine pattern of response after ovulation induction. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic patients in whom 10 had US findings of PCO and 13 patients with PCOS. MAIN OUTCOME MEASURE: Serum estradiol (E2) concentration, number of leading follicles on US, cancellation, and pregnancy rate. RESULTS: Hypogonadotropic patients with US-diagnosed PCO had higher baseline ovarian volume (P less than 0.02) compared with patients with hypogonadotropic hypogonadism with normal ovaries. After ovarian stimulation, a higher mean serum E2 concentration (P less than 0.001), endometrial thickness (P less than 0.001), and increased number of leading follicles (P less than 0.0001) were found in hypogonadotropic patients with US-diagnosed PCO, compared with hypogonadotropic patients with US findings of normal ovaries. Patients with PCOS had a higher serum E2 concentration (P less than 0.008), although they were treated for fewer days (P less than 0.0001) and with fewer ampules of gonadotropin (P less than 0.001) compared with patients with hypogonadotropic hypogonadism with US-diagnosed PCO. CONCLUSIONS: We have characterized a group of hypogonadotropic patients with US findings of PCO, in which the ovarian response to ovulation induction was similar to patients with PCOS. The results have practical and theoretical implications for the etiology and treatment of patients with PCO.

Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients.

OBJECTIVE: To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs. DESIGN: Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Nine patients with isolated hypogonadotropic hypogonadism. MAIN OUTCOME MEASURE: Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation. RESULTS: Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05). CONCLUSION: This study in isolated hypogonadotropic hypogonadism patients is consistent with the two-cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question.

Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotropic hypogonadism.

OBJECTIVE: To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism. DESIGN: An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days, 150 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E2 was > or = 1,100 pmol/L and/or one or more growing follicle > 14 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. SETTING: Specialist Reproductive Endocrinology and Infertility Unit. VOLUNTEERS: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore. MAIN OUTCOME MEASURES: Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies. RESULTS: Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations were very low, and serum E2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted. CONCLUSION: This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E2 indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.

Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS. SETTING: Specialized assisted reproduction unit. PATIENTS: Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration. INTERVENTIONS: After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles. RESULTS: Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates. CONCLUSIONS: Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.

Polycystic ovaries as a relative protective factor for bone mineral loss in young women with amenorrhea.

OBJECTIVE: To examine the impact of polycystic ovaries (PCO) on bone mineral density in amenorrheic women of reproductive age. DESIGN: A retrospective analysis and comparison of polycystic ovarian syndrome (PCOS) with non-PCOS amenorrheic women. A subgroup of patients with ultrasound (US)-diagnosed PCO was also investigated. SETTING: Specialist clinic in reproductive endocrinology. PATIENTS, PARTICIPANTS: Six hundred ten consecutive cases, mean age of 29.8 +/- 7.5 years, with current history of amenorrhea of various causes. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1 to L4) as measured by dual energy x ray absorptiometry, in relation to PCOS, US-diagnosed PCO, and US findings of normal ovaries. RESULTS: Amenorrheic patients with PCOS were found to be younger (P less than 0.001), with higher body mass index (P less than 0.001), were more estrogenized, as measured by endometrial thickness and uterine cross-sectional area (P less than 0.001), and had higher bone mineral density (P less than 0.001) compared with non-PCOS amenorrheic patients. CONCLUSIONS: Patients with amenorrhea because of PCOS and those with US-diagnosed PCO have a higher bone density compared with amenorrheic patients with normal ovaries as detected by US scan.

Cotreatment with growth hormone for induction of spermatogenesis in patients with hypogonadotropic hypogonadism.

OBJECTIVE: To induce spermatogenesis by cotreatment with growth hormone (GH) and gonadotropin therapy in patients with hypogonadotropic hypogonadism who had failed to respond adequately to conventional treatment. DESIGN: Cotreatment with GH (4 IU) and human menopausal gonadotropin, 150 IU of follicle-stimulating hormone and 150 IU of luteinizing hormone (LH), three times a week, and human chorionic gonadotropin, 2,500 IU, two times a week for 24 weeks after unsuccessful treatment for 12 weeks with either pulsatile LH-releasing hormone or gonadotropins. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Seven patients, four of whom had failed to respond adequately to the conventional treatment. MAIN OUTCOME MEASURES: Serum testosterone (T), estradiol, and sperm production, testicular and semen volume, and serum insulin-like growth factor-I and inhibin concentrations. RESULTS: Of the four patients who received cotreatment with GH, three increased T secretion (greater than 11 nmol/L) within a relatively short period of time, two produced adequate amount of sperm (13 and 12 x 10(6)/mL), and one of them impregnated his wife. One patient did not respond. CONCLUSION: The results offer a new approach to the problem of induction of spermatogenesis in patients who respond poorly to conventional treatment because cotreatment with GH enhanced T secretion and sperm production in a relatively short period of time.