Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study.

The effects of oral micronized progesterone on the endometrium and bleeding pattern have been assessed in a multicenter study of 101 postmenopausal patients. During a minimum of 6 cycles, the participants received either percutaneous 17 beta-estradiol (1.5 mg/day) associated with micronized progesterone (100 mg/day), given at bedtime for 21/28 days or 25 days/calendar month (n = 98) [1], or E2 (3 mg/day) for 25 days associated with progesterone (300 mg/day), from day 16 to day 25 (n = 3) [2], according to their willingness to induce, or not, cyclic withdrawal bleeding. Each endometrial biopsy performed at 6-month minimum was assessed by two independent pathologists: results showed 61% quiescent without mitosis, 23% mildly active with very rare mitoses and 8% partial secretory endometrium. The remaining biopsies showed inadequate tissue (4%) or a sub-atrophy (4%). No hyperplasia was found by any pathologist. In the case of inadequate material, the mean thickness of endometrial mucosa measured by ultrasonography was 3.9 mm. Amenorrhea incidence was 93.3 and 91.6% at the 3rd and 6th month of therapy, respectively. No bleeding occurred in more than 80% of women. The results show that a low dose of oral progesterone (100 mg/day), given during 25 days, efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in the majority of postmenopausal women, allowing better compliance to long-term therapy.

[Treatment of impotence with intracavernous auto-injections: moxisylyte diminishes the risks compared to papaverine]. / Traitement de l'impuissance par auto-injections intracaverneuses: le moxisylyte diminue les risques par comparaison avec la papavérine.

The alpha-blocking agent Moxisylyte was tested in auto-intracavernous injections (auto-ICI) in 72 impotent patients. The side-effects were compared to those observed in a group of 34 impotent patients treated with auto-ICI of Papaverine during the same period of time. The Moxisylyte auto-ICI improved 83% of the patients including 68% reporting a complete and durable success. Moxisylyte proved to be safer due to a reduced rate of prolonged erections (1.3% of the patients versus 8.8% with Papaverine) and corporeal fibrosis (1.3% versus 32% with Papaverine). Though less potent than Papaverine, and often seeming insufficient when tested in the office, this type of alpha-blocking agent could be tried in a first time in most candidates to auto-ICI before resorting to Papaverine or Prostaglandin E1 if it fails.

[Outcome of pregnancies obtained by fertilization in vitro. Experience at the V. Olivier Ward (department of Professor Monnier, Lille University Hospital Center) and review of the literature]. / Evolution des grossesses obtenues par fécondation in vitro. Expérience du Pavillon V. Olivier (service du Pr Monnier, CHU de Lille) et revue de la littérature.

The outcome of 87 pregnancies obtained by fertilisation in vitro and progressing beyond 20 weeks of amenorrhea monitored in the Victor-Olivier Ward (Prof. Monnier, Lille Teaching Hospital Group) was analysed. Results were compared with those in the literature. The group was characterised by three features: age, the number of primipara and above all the multiple pregnancy rate. One quarter of FIV pregnancies are multiple pregnancies and almost two newborn out of live are the result of multiple pregnancies. Almost 70 per cent of clinical pregnancies progressed beyond six months. Pregnancy pathology was represented by a marked worsening of the prematurity rate and by a slightly increased risk of fetal under-development. The cesarean section rate was very markedly increased. Sex ratio, and perinatal mortality, malformation and chromosomal aberration rates were similar to those for spontaneous pregnancies. Results are reassuring overall, the pathology being encountered in pregnancies of this type being only partially explained by age, the number of primipara and the multiple pregnancy rate. This pathology could possibly be explained by the underlying situation in which sterility occurred.

[Turner's syndrome and pregnancy in donor oocytes and in vitro fertilization. Three case reports]. / Syndrome de Turner et grossesse par dons d'ovocytes et fécondation in vitro. A propos de trois cas.

It is extremely rare for pregnancy to occur spontaneously in a woman with a mosaic or non-mosaic karyotype 45 x 0. (Till now only 13 patients with a homogeneous x 0 karyotype have been reported out of 62 patients who between them have had 138 pregnancies). Furthermore these pregnancies have been plagued by a number of important complications or fetal malformations (21% have had chromosome anomalies). It is therefore clear that in vitro fertilization with donor oocytes is a tempting solution for these women. The authors having three personal cases try and point out the conditions under which this technique can be used. It is important to realise that from the age of 10 or 12 years these patients have to have hormone treatment in order to avoid hypoplasia and hypovascularization of the uterus. Those conditions explain why so many these women had premature labours and also suffer from pre-eclampsia. Caesarean section was often found to be necessary because of feto-pelvic disproportion.

[Contribution of pure FSH in ovulation induction excluding fertilization in vitro]. / Apport de la FSH pure dans l'induction de l'ovulation hors fécondation in vitro.

The use of pure FSH reduces the likelihood of multifollicular development and increases the safety of ovulation induction without affecting the overall pregnancy rate. The authors propose a "slow" protocol, which is said to provide the same level of safety, but also to increase the number of pregnancies.

[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.

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.

Safety of intracavernous injections using an alpha-blocking agent.

We tested the possibility of using intracavernous injections of the alpha-blocking agent moxisylyte (6-acetoxy-thymoxy-ethyl-dimethylamine) as treatment of erectile impotence. Laboratory studies proved moxisylyte to be more active than saline (double-blind with crossover) but less active than papaverine (crossover), since it induced prolonged erection in most patients but rigid erection in only a few. However, penile vibration proved to enhance the moxisylyte effects, the combination resulting in rigid erection in 5 of 8 patients tested. Repeated office injections of moxisylyte in 70 patients resulted in clear improvement of impotence during the subsequent weeks in 50 per cent of the psychogenic, and 18 per cent of the organic and mixed impotent patients. Of 91 impotent patients 42 achieved satisfactory intercourse within 2 hours after an office injection, although previously the same dose induced a rigid erection in the office in only 24. Of 37 patients instructed in moxisylyte self-injections 92 per cent achieved successful results without any significant side effect. The main advantage of moxisylyte proved to be its safety, allowing for less compelling precautions than with papaverine: only 2 of the 170 patients injected with moxisylyte at our clinic had prolonged erections, that is 1.1 per cent compared to 14 per cent in a personal series who received papaverine. In regard to the therapeutic applications of intracavernous injection facilitating drugs, such as moxisylyte, should be tried first, with use of the more potent but also more dangerous drugs, such as papaverine, only when impotence fails to improve.

[Treatment of the gynecologic consequences of hyperandrogenism]. / Traitement des conséquences gynécologiques des hyperandrogénies.

Whether they are of adrenal or mainly ovarian origin, hyperandrogenisms result in consequences on cycle and fertility. In addition to the treatment of hyperandrogenism itself, it is advisable to know how to prevent the gynaecological consequences of the abnormality.

[Impotence due to venous incompetence. Research on reliable diagnostic criteria]. / Impuissance par fuite veineuse. A la recherche de critères diagnostiques fiables.

"Venous incompetence" is thought to be an organic cause of impotence. Its diagnosis is usually based upon Artificial Erection Test (AET); now, the reliability of this procedure is contested. We tested it in 9 controls, 13 psychogenic impotent patients and 65 impotent patients presenting "venous incompetence" according AET (maintenance flow rate needed for erection--MFR greater than 75 ml/min). Organicity of impotence was evaluated by Nocturnal Penile Tumescence monitoring and by the results of a sex-therapy. AET reproducibility was tested in 24 cases. The interest to perform an intracavernous injection of 80 mg papaverine before AET was tested in 18 impotent patients. Our results confirm that MFR is the most reliable criterion for interpreting AET. But 15% of the impotent patients with a MFR greater than 120 ml/min, 32% of those with a MFR greater than or equal to 80 ml/min and 66% of those with a MFR between 80 and 120 ml/min were in fact psychogenic patients. Moreover, we found "excessive" MFR in 3 of the 13 psychogenic patients and one of the normal controls (160 ml/min). In 50% of our patients, AET results were not reproducible. Injecting papaverine before AET significantly reduces MFR, but false positive results do still exist. Some recent physiopathologic data suggest that AET performed after papaverine injection might logically be disturbed by stress. These data should incite to be cautious when interpreting AET results, and results of "venous incompetence" surgery.

[Diagnostic and therapeutic applications of intracavernous injection of vasoactive drugs in impotence. Defense for the use of facilitating drugs. Part I--Pharmacology, classification and complications of active drugs]. / Applications diagnostiques et thérapeutiques des injections intracaverneuses (IC) de drogues vasoactives dans l'impuissance. Plaidoyer pour l'utilisation des drogues facilitatrices. Partie I--Pharmacologie, classification et complications des drogues actives.

The article discusses drugs which promote erection when injected via the intracavernous (IC) route during consultation. The diagnostic and therapeutic applications in the treatment of impotence are discussed also. 25% of impotent patients noted an improvement after this treatment while 50% of patients suffering from impotence of psychological origin noted an improvement. Auto-injection is also discussed. IC treatment now seems justified in most cases which have not responded to traditional therapeutic approaches and this includes cases of psychological origin. Vasoactive drugs can be described as being inducers (use of these drugs induces a rigid erection, even in the presence of the doctor), facilitating drugs (which produce a rigid erection only if sexual stimulation is present also) and inhibitors (which stop the erection). The former group (which has papaverine as leader) produces a significant number of side effects, not least of these being priapism; there is a risk of lasting iatrogenic impotence which is not negligible. These risks are reduced considerably when one uses facilitating drugs which, although less powerful, suffice in treating a large proportion of cases of impotence. Papaverine can not be replaced as a diagnostic drug but facilitating drugs should be used first in therapy and inducers should be used only if these facilitating drugs have failed.

[The wife of the impotent person. Key element in the prognosis]. / La femme de l'impuissant. Elément clef du pronostic.

The authors develop the key position of the wife in male impotence, even if organic. This influence may be positive or negative and plays an important role in the prognosis.

[Retarded ejaculation and anejaculation without orgasm. Apropos of the results of studies and of treatment in 60 cases]. / Ejaculation retardée et anéjaculation sans orgasme. A propos des résultats des explorations et du traitement dans 60 cas.

The physiological mechanism of ejaculation is recalled. The different kinds of abnormalities of ejaculation and their etiologies (drugs, post-surgery, neurological, endocrinological, psychological) are specified. The diagnosis and the therapeutical management of the different varieties are discussed and the results of a personal experience of 60 cases are reported.

[Critical evaluation of hidden organic factors causing impotence]. / Evaluation critique des facteurs organiques cachés de l'impuissance.

Many studies have pointed out the possibility of "masked" organic factors in erectile impotence, detectable only by means of laboratory investigations: mild hypogonadism, hyperprolactinemia, occlusions selectively located at the site of the sexual arteries, venous incompetence, subclinical neuropathies. This paper critically reviews these conditions, and the methods proposed to diagnose them. Impotence is a multifactorial disorder, involving in most cases psychological factors. Among the preceding conditions only severe venous incompetence can induce impotence only by itself. The other masked organic factors play only a partial role in most cases and need to be potentiated by another organic or psychological factor. In our experience, masked organic factors are present in 50% of the impotent males. But they play a significant role in only 25%.

["Hidden" organic causes of impotence. Diagnostic methods and critical evaluation of their responsibility]. / Les causes organiques "cachées" de l'impuissance. Méthodes diagnostiques et évaluation critique de leur responsabilité.

In five per cent of impotent, sexual dysfunction obviously results from an organic factor which can be today qualified as "classical". "Hidden" organic factors have also been implicated in a variable ratio of the other cases. This paper constitutes a critical review of the role they play in impotence, and of the methods allowing their detection. On one hand, methods allowing evaluation of the respective responsibilities of organic and psychogenic factors (the most important of which remain nocturnal penile tumescence monitoring); on the other hand, specific investigations of each factor. It is no longer possible to deny the existence of "hidden" organic factors in impotence. These factors intervene to varying degrees in one third of cases. Among them erectile failure only by themselves. Hyperprolactinaemia, moderate hypogonadism, infraclinical neuropathies, arterial stenoses and moderate venous leakages seem to play a partial role of organic starter or cofactor, the sexual consequences of which are amplified by psychological factors, partly secondary to the initial sexual failures. Nevertheless, the conjunction of several "hidden" organic factors may probably be sufficient to induce an impotence without involvement of psychological factors.