Continuation and effectiveness of tadalafil once daily during a 6-month observational study in erectile dysfunction: the EDATE study.

AIMS: This was the first observational study evaluating treatment continuation, effectiveness and tolerability of tadalafil 5 mg once daily (TAD-OaD) in patients who chose and paid for treatment of erectile dysfunction (ED) in routine clinical practice. METHODS: Men ≥ 18 years with ED, treated previously with phosphodiesterase type 5 (PDE5)-inhibitor on-demand (PRN) or treatment-naïve, were enrolled at 59 sites. For patients prescribed TAD-OaD at baseline (T1), change in erectile function (IIEF-EF and GAQ) was documented after 1-3 (T2) and 4-6 (T3) months. The primary outcome was the probability to switch/discontinue from TAD-OaD, estimated by Kaplan-Meier (KM) product-limit method. Changes in IIEF-EF were evaluated using a mixed model for repeated measures adjusting for patient baseline characteristics. RESULTS: Of 975 men enrolled (median age 56.8 years, 33.7% with previous PDE5-inhibitor use), 778 were prescribed TAD-OaD, 135 TAD-PRN and 62 sildenafil or vardenafil PRN. During the 6-month longitudinal observation, 107 patients (13.8% of 778) switched or discontinued TAD-OaD-treatment. KM-rates (95%CI) for continuing TAD-OaD at 2, 4 and 6 months were 94.0% (92.3, 95.7), 88.3% (85.9, 90.6) and 86.3% (83.7, 88.9), respectively. The 25th percentile of time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks (lower 95%CI 30.3 weeks). At T3, IIEF-EF scores had increased by 7.1 (LSmean; 95%CI 5.8, 8.5) points; 91.3% of patients reported improved erections. The most frequently reported AE was headache (10 patients; 1.3%); no new/unexpected safety signals were observed. CONCLUSION: Under routine conditions, and when patients were involved in treatment decision-making, more than 86% of men starting/switching to tadalafil once daily (OaD) at baseline continued tadalafil OaD treatment for ≥ 6 months.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction.

AIMS: Erectile dysfunction (ED) is a common comorbidity in men with diabetes mellitus. Tadalafil 10 or 20 mg taken on demand is efficacious and safe for men with diabetes and ED. Recently, continuous treatment with tadalafil has been proposed, addressing ED management as any other chronic condition. This study examined whether once-daily tadalafil 2.5 and 5 mg is efficacious for men with diabetes and ED. METHODS: This randomized, double-blind, placebo-controlled, multicentre, 12-week study enrolled 298 men with diabetes and ED to once-daily treatment with placebo, tadalafil 2.5 mg or tadalafil 5 mg. Primary efficacy measures were International Index of Erectile Function Erectile Function (IIEF EF) Domain score, and patient success rates for vaginal penetration and completion of intercourse. Patient satisfaction, endothelial function biomarkers, and safety were also assessed. RESULTS: Patients receiving either dose of tadalafil had clinically and statistically significant improvements in IIEF EF and statistically significant improvements in mean success rates for vaginal penetration, completion of intercourse, and overall treatment satisfaction (P < or = 0.005 tadalafil vs. placebo, all measures). Endothelial dysfunction biomarkers were unchanged. The most common adverse events were headache, back pain and dyspepsia. CONCLUSIONS: In this first study of men with diabetes and ED, once-daily tadalafil 2.5 and 5 mg was efficacious and well tolerated, suggesting this may be an alternative to on-demand treatment for some men, eliminating the need to plan sex within a limited timeframe.

A double blind controlled study of the hormonal and clinical effects of bromocriptine in the polycystic ovary syndrome.

Previous studies on the efficacy of bromocriptine for the treatment of patients with the polycystic ovary syndrome failed to include control groups. This study, therefore, was undertaken to determine the clinical and endocrine effects of bromocriptine and a placebo (given in a random double blind fashion) in 55 patients with PCOS. The plasma levels of estrone, estradiol, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, and serum PRL and gonadotropins (LH and FSH) were measured before treatment. In addition the serum PRL response to TRH and the serum LH and FSH response to GnRH were determined. The effects of acute administration of bromocriptine (2 X 2.5 mg at 12-h intervals) on serum gonadotropins and their response to GnRH were studied to explore the possibility that this test might predict the response to chronic bromocriptine treatment. Bromocriptine then was given at an initial dose of 1.25 mg twice daily. If no clinical improvement occurred 2.5 mg were given twice daily for at least 6 months. Hormonal measurements and dynamic tests were repeated after 3 and 6 months of therapy. The endocrine profile of the two groups was not different before treatment. The clinical results were not better in the treatment group than in the placebo-treated patients: therapy was successful (restoration of ovulatory cycles of less than 35 days duration) in 12 of 28 patients taking bromocriptine vs. 8 of 27 taking placebo. Slight improvement (1 or 2 ovulations) occurred in 3 of 28 vs. 3 of 27, and failure (no clinical change) in 13 of 28 taking bromocriptine vs. 16 of 27 taking placebo, respectively. Serum PRL fell significantly in the bromocriptine group, and there was a significant fall in the serum LH response to GnRH in both groups. No hormonal measurement or response predicted the clinical response to treatment. The only significant effect of chronic bromocriptine therapy (5 mg/day) in patients with the polycystic ovary syndrome was to lower the serum PRL concentration.

Clinical and biological phenotypes in late-onset 21-hydroxylase deficiency.

We analyzed data from 20 patients with late-onset 21-hydroxylase deficiency (LOHD). Three clinical phenotypes could be distinguished among the 18 women. Seven (39%) presented with clinical features suggesting polycystic ovarian disease (PCOD). However, despite androgen levels similar to those of patients with typical PCOD, high serum LH to FSH ratios were not consistently found. Seven other women (39%) presented with isolated hirsutism, suggesting idiopathic hirsutism. The remaining 4 women (22%) had no manifestations of androgen excess and were considered to have the cryptic form of LOHD. Serum 17-hydroxyprogesterone (17-OHP) and androgen levels were similar in the 3 phenotypes, suggesting that the clinical expression of LOHD in women is modulated by individual factors, such as androgen sensitivity. The 2 men were detected by family study and were clinically normal. Since clinical diagnosis of LOHD is impossible, we concentrated on hormonal data with the aim of providing guidelines for the biological diagnosis of LOHD. Assay of basal serum 17-OHD at 0800 h in both sexes and in the early follicular phase in women was sufficient to establish the diagnosis of LOHD in most patients. If doubtful results are obtained, i.e. serum 17-OHP levels between 2 and 5 ng/ml, an ACTH test must be performed. Post-ACTH serum 17-OHP levels exceeding 10 ng/ml confirm the diagnosis of LOHD. Such results should avoid confusion with heterozygotes for 21-hydroxylase deficiency, whose frequency is high within the general population and may be even higher in patients with idiopathic hirsutism or PCOD.

Human chorionic gonadotropin treatment of nonorganic erectile failure and lack of sexual desire: a double-blind study.

Forty-five cases of nonorganic failure (n = 39) or lack of sexual desire (LSD, n = 6) were treated for one month, either with human chorionic gonadotropins (HCG, 5,000 IU I.M. twice per week) or with placebo using a double-blind method. HCG gave better results than placebo (47% vs 12%, p less than 0.05) and improved a higher number of sexual parameters (6/7) than placebo (2/7). HCG effect on sexual behavior did not correlate with the increase in plasma testosterone level: it seems HCG is a useful option in sexologic treatment of erectile failure and LSD.

Hyperprolactinemia and sexual function in men: a short review.

Erectile dysfunction (ED), generally associated with reduced sexual desire and sometimes with orgasmic or ejaculatory dysfunction, is the major revealing symptom of hyperprolactinemia (HPRL) in men, a condition that should not be neglected since many cases result from pituitary tumors, likely to result in serious complications. It is generally believed that the mechanism of the prolactin (PRL)-induced sexual dysfunctions is a decrease in testosterone secretion. In fact, serum testosterone is normal in many hyperprolactinemic males and there are also testosterone-independent mechanisms, probably mainly set at the level of the brain's neurotransmitter systems. Systematic determinations of serum PRL found very low prevalences of marked HPRL (>35 ng/ml) in ED patients (0.76% in a compilation of over 3200 patients) as well as of pituitary adenomas (0.4%). In addition, the association of HPRL with ED may have been coincidental in some of these cases, since 10% of the HPRLs diagnosed by the usual immunological assays are composed of macroprolactins, which are biologically inactive or little active variants of PRL. Their identification requires a PRL chromatography that is restricted to some specialized laboratories. There is presently no consensus with regards to the screening for HPRL in ED: systematic determination of serum PRL may be justified since HPRL is a serious but reversible disease, while there is presently no reliable clinical, psychometric or hormonal criteria (including serum testosterone level) allowing to restrict its determination to certain categories of the ED patients without risk of neglecting some HPRLs. In case of consistent HPRL, searching for a hypothalamic or pituitary tumor is mandatory. Dopamine-agonist therapy is the first choice treatment for the PRL-induced sexual dysfunctions. Additional sexual counselling may be necessary for certain patients.

Acceptance, efficacy and preference of Sildenafil in patients on long term auto-intracavernosal therapy: a study with follow-up at one year.

PURPOSE: To assess the acceptance, long term efficacy and preference of Sildenafil in impotent patients previously on auto-intracavernosal therapy. MATERIALS AND METHODS: The patients were the 107 men (mean age 58.4 y) on auto-intracavernosal therapy (auto-IC) for more than 6 months (mean duration 32.7 months >12 months in 100) who were consecutively seen within 6 months of the launch of Sildenafil in France. If there was no contra-indications to Sildenafil they were proposed a trial of Sildenafil at home. Following this trial they were given the possibility to change their therapy and were followed for 1 y at 3 months intervals. RESULTS: Three patients had contra-indications to Sildenafil. Of the remaining 104, 45 (43%) refused the trial, mainly because they were afraid of possible cardiac risks (n=21, including 51% of the psychogenic and mixed patients compared to 8% of the predominantly organic ones). Among the 59 who tried it, Sildenafil gave good results in 46 (78%), including 100% of the predominantly psychogenic and 61.5% of the predominantly organic ones) with minimum effective doses of 25 mg in 7, 50 mg in 18 and 100 mg in 21. It failed in 9 (15%) and gave average results in 4 (penetration with a non fully satisfying erection). There was a clear relationship between the sensitivity to Sildenafil and that to Alprostadil, the vasoactive agent predominantly used for the auto-ICIs. Every 46 patients with good result of Sildenafil elected to continue with this drug, including 3 who used both Sildenafil and auto-ICIs in alternance. Every 4 patients with average results elected to continue with auto-ICI including 1 who also used Sildenafil in alternance. Five of the 50 patients with good or average results were lost to follow-up within 6 months. At the 1 y follow-up visit, 43 of the 45 others were still using Sildenafil, in alternance with auto-ICI in 1. No one reported a decrease in efficacy with time. The 2 patients with average results still in the study were on auto-ICIs. CONCLUSION: Sildenafil is highly effective in the impotent men previously treated with auto-ICI and its efficacy is maintained at least for 1 y. When tried and effective it is preferred by most men but almost half of our patients refused trying it.

Intracavernous pharmacotherapy: comparison of Moxisylyte and prostaglandin E1.

We report in this retrospective study the results obtained with the first two drugs proposed to reduce the relatively high rates of priapism and fibrosis bound to the papaverine intracavernous injections, i.e. the alpha-blocking agent Moxisylyte (Mox), and prostaglandin E1 (PGE1). Each drug was used for auto-injections in 130 patients with a comparable mean follow up (14.8 months with Mox compared to 14.6 with PGE1). PGE1 proved to be significantly more efficacious (good results in 71% of the patients vs 50% with Mox), especially in the arteriogenic patients (respectively 96% vs 46%). Conversely PGE1 induced prolonged erections in significantly more patients (11 vs 1 with Mox), including 2 priapisms, and also induced pain in more patients (12 vs 1 with Mox). The rate of fibrotic nodules and plaques was low (2 and 3 patients). Despite the better tolerance of Mox, its continuation rate was significantly lower than that of PGE1, PGE1 can be the first choice agent in most cases. Mox is mainly indicated in the patients with supersensitivity to the injections and in those with significant pain following PGE1.

Intracavernous Alprostadil Alfadex--an effective and well tolerated treatment for erectile dysfunction. Results of a long-term European study.

Long-term efficacy and safety of Alprostadil-Alfadex (EDEX/VIRIDAL) in intracavernous self-injection therapy for chronical erectile failure was investigated in a four year running multicenter European trial. Of the 16,886 protocolled injections 93% (15,713) resulted in rigid erections followed by successful sexual intercourse. Reported side effects by patients were prolonged erections > 6 h only occurring during the first year in 1.2% (2 out of 162), painful erections in 29% (47 out of 162) during the first year and decreasing to 12.1% by year 4, hematomas, neither requiring therapeutic measures nor impeding sexual performance in 33.3% (54 out of 162) in year 1 with a decrease to 12.1% by year 4, fibrotic penile alterations such as nodules, plaques or deviations in 11.7% (19 out of 162) with spontaneous healing in 48% (9 out of 19). Of the 162 patients involved in this trial 54 completed the 4 y. Of the 54 completers 91.4% considered the tolerability good or very good and were satisfied or very satisfied with self-injection therapy with Alprostadil-Alfadex. The respective rates of the female partners were 51.7% very satisfied and 39.7% satisfied. These data of the world-wide longest running prospective trial with a vasoactive drug in self-injection therapy provided impressive proof that Alprostadil-Alfadex represents a very effective and safe treatment for erectile dysfunction of both psychogenic and organogenic origin.

Luteal support after luteinizing hormone-releasing hormone agonist for in vitro fertilization: superiority of human chorionic gonadotropin over oral progesterone.

It has been reported that the pregnancy rate after in vitro fertilization (IVF) after pituitary desensitization with luteinizing hormone-releasing hormone agonist (LH-RH-a) is twice as low if the luteal phase is not supported. We therefore tested the respective advantages of luteal support using human chorionic gonadotropin (hCG, 1,500 IU three times) and progesterone (P, micronized, oral administration, 400 mg/d) after 171 embryo transfers (ET) in which the cycle was stimulated with the LH-RH-a triptoreline. The type of luteal phase support was randomly selected except when the estradiol level exceeded 2,700 pg/mL. The clinical pregnancy rate and the ongoing pregnancy rate were significantly higher using hCG (after the transfer of 3 embryos, 45% and 43% with hCG versus 23% and 17% with P). The same results were noted for the embryo implantation rate per ET (19% of embryos are viable after 6 months of pregnancy after hCG versus 7.5% after P). Adequate luteal support, therefore, significantly improves the results of IVF when LH-RH-a are used. The poor results obtained with P in this study might be related to its poor bioavailability after oral administration.

A randomized trial of human chorionic gonadotropin support following in vitro fertilization and embryo transfer.

This article reports on the effects of human chorionic gonadotropin (hCG) on progesterone (P) and estradiol (E2), luteal phase length, and conception in 116 cycles treated by in vitro fertilization and embryo transfer (IVF-ET). In 60 cycles, the luteal phase was supported by hCG, 1500 IU three times at 2-day intervals from the day of ET. The remaining 56 cycles served as controls. hCG significantly increased the P level (93 +/- 53 versus 62 +/- 46 ng/ml), the P/E2 ratio, and the luteal phase length (17.4 +/- 1.3 versus 12.2 +/- 1.7 days). However, the total pregnancy rate did not significantly differ between the two groups, though the pregnancy rate after transfer of two or three embryos was slightly higher in the hCG group (26.9 versus 22% in the control group), as was the rate of implanted embryo per transferred embryo after transfer of two or three embryos (25 versus 15.3%). It was concluded that, while hCG increased the magnitude and duration of the luteal P secretion, it did not clearly improve the pregnancy rate.

Purified follicle-stimulating hormone in polycystic ovary syndrome: slow administration is safer and more effective.

Twenty-seven infertile patients presenting with clomiphene citrate- (CC) resistant polycystic ovary syndrome (PCOS) were treated with purified urinary follicle-stimulating hormone (pFSH). We compared the conventional stepwise protocol with a slow protocol starting with 75 IU/d, not increased until 14 days, supplemented by human chorionic gonadotropins (hCG). The slow protocol was characterized by a slightly longer duration of stimulation but a more physiological ovarian response (mono- or biovulatory cycles in 70% versus 19% with the conventional protocol, less follicles, and a lower plasma estradiol [E2] resulting in significantly less discontinuation of treatment for risk of hyperstimulation or multiple birth). The pregnancy rate per cycle was higher with the slow protocol (23% versus 15%). The slow protocol could thus be the treatment of choice for CC-resistant PCOS, as it appeared safer and more effective.

Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen.

Twenty-five subfertile men, all presenting with idiopathic normogonadotropic oligospermia, were treated with tamoxifen (20 mg/day) for 4 to 12 months. Semen analysis was performed twice before treatment and at least twice after 3 to 12 months of treatment. In 14 patients, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and plasma testosterone (T) were assayed before treatment, then again after 2 weeks and 12 weeks of treatment. Semen volume, sperm motility, and sperm morphologic characteristics were not modified by tamoxifen. Conversely, a twofold increase of both the mean sperm concentration and the mean total sperm count per ejaculate was observed during treatment (P less than 0.001). Mean values of T, LH, and FSH increased during treatment, but the difference was only significant for T (P less than 0.001) and FSH (P less than 0.05). Ten pregnancies (40% of cases) were reported during the 161 months of treatment.

Acute effects of bromocriptine on gonadotropin secretion in polycystic ovary syndrome.

Thirty-two women presenting with polycystic ovary syndrome (PCO) were studied on 3 consecutive days. On day 1, plasma androstenedione, testosterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), estrone (E1), estradiol, serum prolactin (PRL), and PRL response to thyrotropin-releasing hormone were determined. On day 2 the patients were given two placebos at 1-hour intervals; then serum PRL, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and the LH and FSH responses to LH-releasing hormone (LH-RH) were determined. On day 3 the patients were given two 2.5-mg tablets of bromocriptine (BRCR) at 12-hour intervals; then serum PRL, LH, and FSH and the LH and FSH responses to LH-RH were again determined. After BRCR, mean values of basal serum PRL (P less than 0.001), LH (P less than 0.05), and FSH (P less than 0.001) and the FSH response to LH-RH (P less than 0.01) fell with respect to the values determined on day 2. Our group of patients was heterogeneous regarding the effects of BRCR upon the LH response to LH-RH. Of 32 women undergoing the trial, 17 did not respond to BRCR (change of the LH response to LH-RH less than 33% with respect to day 2). They were called "nonresponders." Among the 15 who responded to BRCR, 10 decreased their LH response greater than or equal to 33% ("decreasers") and 5 increased their LH response greater than or equal to 33% ("increasers"). Decreasers had mean values of serum PRL, plasma E1, DHEA-S, and 17-OHP higher than nonresponders (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Sexuality of the diabetic woman]. / La sexualité de la femme diabétique.

Diabetes Mellitus frankly increases the prevalence of sexual problems in men, mainly in the form of erectile dysfunctions. Its effects on sexual function of the diabetic women have been less objectively studied, due to cultural reasons and methodological difficulties. The different phases of the sexual cycle, as well as their physiological control, are similar in human males and females. Several studies suggest an increased prevalence of sexual problems also in diabetic females. Their rate seems similar to that of the males. An increased prevalence of Female Sexual Arousal Disorder has been found in 6 studies of 6 comparing diabetic to non diabetic females. Its main symptom was a deficient vaginal lubrication, making sexual intercourse unpleasant. This disorder is the female equivalent to erectile dysfunction. It probably results from similar mechanisms, involving damages in the vascular and autonomic nervous systems, as well as alteration in the nitric oxide production and efficacy. The prevalence of Hypoactive Sexual Desire Disorder was also increased in most studies (5 of 8, significantly in 3). This could result from the increased prevalence of depression in diabetic females. The Dyspareunia's prevalence was not significantly increased (0 of 6 studies). Available figures are not consistent as regards the orgasmic disorders (prevalence increased in only 4 of 8 studies). No significant correlation of female sexual dysfunction with diabetes duration, balance, or complications has been found. Conversely some significant correlations with depression or poor acceptance of diabetes have been found, supporting a causative role of psychological factors. Although still limited the therapeutic options should not be neglected. Merely prescribing a water soluble lubricating gel may greatly improve the sexual life of couples. Doctors should talk themselves about sexual function with their female diabetic patients. Most of these are too much embarrassed to ask themselves their doctor, although their sexual problems may seriously interfere with their quality of life and that of their partner.

[Evaluation of hormonal treatments for idiopathic oligospermia]. / Bilan des traitements hormonaux de l'oligospermie idiopathique.

Many hormonal treatments have been tried in idiopathic oligospermia because of the physiologic roles of the hormones FSH and testosterone in regulation of spermatogenesis, the possibility of increasing spermatogenesis in normal monkeys by increasing their serum FSH up to supraphysiologic levels, and of several hormone abnormalities reported in this condition (abnormal pulsatile release of LH and thus probably of LHRH, abnormal bioactivity of FSH, compensated hyperestrogenism). None of these treatments proved to be effective until now, though a modest beneficial effect cannot be totally excluded for some of them, because of the poor discriminating power of most of the trials. Many methodological difficulties do indeed hamper the objective assessment of male infertility treatments. Pulsatile administration of LHRH, human menopausal gonadotropins, androgens, bromocriptine, and angiotensin-converting enzyme inhibitors are definitely uneffective or without practical interest. A beneficial effect of the anti-estrogens clomifene and tamoxifene cannot be excluded. It would be modest, increasing the annual pregnancy rate from 18 to 30%, only in case of normogonadotropic oligospermia. The possibility of increasing the vitro fertilization success rate by treating the oligospermic males with purified FSH needs confirmation. Whatever the benefit, it would not reach the success rate of intracytoplasmic injection of spermatozoa.

[Ovulation disturbances in athletes and their mechanisms]. / Perturbations de l'ovulation des sportives et leurs mécanismes.

Delayed menarche, amenorrhea or at least luteal insufficiency are frequent in athletic women, when in intense athletic training. The origin of these disturbances seems to be plurifactorial. The main responsible parameters seem to be: the physical and psychological stresses; nutritional factors often associated with reduced food intake (specially reduced protein and increased vegetable fibers intake), and in some cases with loss of body fat; and affective problems responsible for eating disorders. The paper describes the acute effects of training upon hormones, and the hormonal profile of athletes when in intense training. The reduced or suppressed LH pulsatile secretion determines the ovulatory disturbances. Among the responsible factors, the rise of opioids, as beta-endorphin, and the corticotropin hyperactivity, which probably play an important role, even if other mechanisms will be demonstrated later.

[Changes in the gonadotrophins, in the prolactin and in the sexual steroid levels throughout the normal menstrual cycle (author's transl)]. / Variations des gonadotrophines, de la prolactine et des stéroïdes sexuels au cours du cycle menstruel normal.

The authors describe the hormone changes that occur in a normal woman throughout the menstrual cycle. These is no circadian rhythm in the release of gonadotrophins after puberty. LH is liberated in a pulsatile way throughout the day and the periodicity and amplitude of the episodes vary throughout the cycle with a notable peak of this hormone before ovulation. The level of FSH is greater early in the follicular phase and in mid-cycle, where there is also a cycle together with that of the LH. In spite of these variations a single estimation of gonadotrophins does represents their secretion over 24 hours. The changes in total and free oestradiol and in oestrone are parallel. There are two maxima, the one being preovulatory and preceding the gonadotrophin peak and the other throughout the whole luteal phase. Progesterone changes little throughout the day. It is low during the follicular phase and gradually starts to rise before the preovulatory peak of gonadotrophins, and stays raised throughout the whole luteal phase, following during this phase a variable curve. The 17 hydroxyprogesterone is similarly low in the follicular phase. Its cycle peak is stronger and its rise in the luteal phase weaker than that of progesterone. The secretion of androgens is marked by changes throughout the day of a circadian nature (maximal for dehydroepiandrosterone and delta 5 androstenediol) and cyclic (especially for androstenediol which rises in mid-cycle). Prolactin secretion is marked by changes throughout the day, circadian (maximum during the night) and cyclical (minimum follicular, maximum preovulatory, with a luteal level higher than the follicular level). These changes should be considered in order to work out correctly the levels of hormones that should be prescribed on the precise dates and worked out in accordance with the date of menstruation and temperature curve taken throughout the cycle.

[Induction of ovulation in 1985]. / L'induction de l'ovulation en 1985.

There are many methods that can be used to induce ovulation when there is a fault in ovulation in patients who have normal prolactin levels. These are: Bringing the weight to a normal level. Giving Clomiphene. Giving Tamoxifen. Giving cyclofenil and bromocriptine, which really have no more effect than giving a placebo. Giving gonadotrophins in a classical way. This is very useful where there is hypogonadic amenorrhoea but much less useful when the failure of ovulation occurs with normal gonadic function. It is accompanied by a risk of multiple pregnancies and of hyperstimulation, which should be monitored by ultrasound very strictly so that it cannot become too serious. The use of purified FSH which theoretically should be more adequate, at least in cases where the gonadic function is normal in spite of failure of ovulation. Pulsatile administration of LHRH, which in cases of hypothalamic amenorrhoea carries less total risk than giving gonadotrophins. Finally, wedge resection of the ovaries which is reversed for polycystic ovaries that are larger than normal in size, and allied methods. The first choice for hypogonadic hypothalamic amenorrhoea would seem to be the LHRH pump; and for failure of ovulation with normal gonadic function Clomiphene or Tamoxifen. When anti-oestrogens fail to correct these latter cases one can choose according to the case between gonadotrophins, choosing if possible pure FSH, and/or wedge resection. In the last resort in these cases the LHRH pump can be used. The frequent failure of these methods show that perhaps it is possible to create a hypogonadotrophic hypogonadism by giving agonists for a long time or antagonists to LHRH in such a way that a second attempt can be made to induce ovulation using gonadotrophins in better conditions of efficacy and safety.