[Ovarian gonadotropic inhibition and endometriosis. About fighting false dogmas...]. / Inhibition gonadotrope et endométriose. Comment lutter contre les dogmes s'ils sont erronés ?

Ovarian gonadotropic inhibition is today an efficacious tool in the treatment of endometriosis mainly when associated with surgery and sometimes by itself. However, to be useful, this inhibition must be stable - without any cyclical looseness - of long duration, sometimes during years and sufficiently powerful. Depending on the severity of symptoms and that of the disease, the choice will be among GnRH agonists, gestagens and combined OCs. The recent development of continuous oral contraception with protracted amenorrhoea makes treatment by continuous hormonal administration easier for the patients with endometriosis.

[Endometriosis and surviving adolescence]. / Endométriose et vécu de l'adolescence.

Endometriosis is a recurrent and painful disease which sometimes disturbs severely the quality of life of women who suffer from it. It is then logical to include a psychological back-up to its medical and surgical treatment. Nevertheless this support is not often offered to patients. One can hypothesize another and completely different way of seeing the problem: the mood swings and depression of endometriotic patients could possibly be, at least in some of them, the cause of the graft of endometrial cells and not the effect of pain and infertility. The mechanism of the development of endometriotic lesions could be related to a lowering of immune defences due to an alteration of the psycho-neuro-endocrino-immunologic network, resulting from difficult life experiences which mostly happen during adolescence. This concept may have beneficial effects for the patient whose case would be more understood in depth. But very few medical teams consider it worthwhile to include in their practices.

[Endometrial hyperplasias resistant to progestins: alternatives to traditional treatments]. / Les hyperplasies endométriales résistant aux progestatifs: alternatives aux traitements traditionnels.

Endometrial hyperplasias are mainly regarded as a response to unopposed endogenous estrogenic stimulation and concern 12% of perimenopausal women. They are usually diagnosed because of irregular bleeding. They are divided into two categories based on the presence or absence of cytological atypia and further classified as simple or complex according to the extent of architectural abnormalities. Endometrial hyperplasias with cytological atypia are classically treated by hysterectomy. Endometrial hyperplasias without cytological atypia are classically treated by progestins. The bad observance (25% spontaneously stopping), the 30% recurrence rate after stopping progestin and the 12-53% resistance rate to treatment lead to propose a second-line therapy after endocrinological check-up, exploration of haemostasis, pelvic ultrasonography, hysteroscopy and endometrial biopsies. Standard treatments include uterine curettage which is not very effective and hysterectomy. Medical alternatives (gonadotropin-releasing hormone agonists, levonorgestrel-releasing intrauterine device) and surgical alternatives (endometrial resection, thermal balloon endometrial ablation) were developed to avoid treating functional pathology radically. These conservative procedures correct 80% of endometrial hyperplasia symptoms with a low rate of lateral effects. However, these results need to be confirmed by long-term studies. Some economical, legal or material factors can also limit carrying out the procedures. Clinical trials need to be performed to better define the place of medical and surgical alternatives to hysterectomy in the treatment of endometrial hyperplasias resistant to progestins.

[DHEA: desire and resistance]. / La DHEA: désir et résistance.

DHEA is a prohormone that is secreted by the corticoadrenal glands on a nyctohemeral rhythm alike to that of testosterone. Its plasmatic level gets reduced with ageing in a great amount of individuals, but not in all. Moreover, DHEA is a neurosteroid synthesized by certain neurons. As shown by correlation studies, lowered levels of DHEA wre linked to a higher death rate, in part of the studied population. Besides, an improvement in well being as well as in some mental functions, after a 50 mg daily intake, was shown in preliminary studies. Many well-conducted studies followed which only partially confirmed the previous ones. Nowadays, it seems to be taken for granted that DHEA becomes estrogens and androgens and that its action on women is mainly an androgenic one. DHEA becomes active after intracellular transformation, which varies according to the enzymatic set of cells. Some effect on elderly women's libido, and improvement in erectile dysfunction in men without vascular pathology but a lowered DHEA level, has been observed. Thus, using DHEA in order to cure sexual troubles might be considered, although the possible negative effects of DHEA, especially on breast and prostate, have not been discarded yet. The conditions under which it could have a beneficial effect on mental functions remains to be discovered. Acknowledgement of those pathological situations, in which DHEA could prove useful, as well as the administration posology is, therefore, crucial.

[The ovary and insulin resistance]. / L'ovaire de l'insulinorésistance.

Insulin resistance appears to be responsible of approximately half of the cases of polycystic ovaries, the other half being probably provoked by an anomaly of the stimulation of ovaries by an excess of LH. Nevertheless, it is likely that in most cases the two factors conjugate. The excess of androgen production by the ovarian stroma is one of the major symptoms of this disease. Today, however, the diagnosis is carried mainly with the assistance of ultra-sounds which, besides the increased ovarian volume, have permitted to discover an increased ovarian stromal vascularity. Two essential datas derive from the whole works: the increased frequency of ovarian hyperstimulation syndrome and the great number of metabolic complications which requires an endocrinological supervision. But the most recent works focus on the extension to all ages of this form of pathology: from the intra-uterine life to the post menopause; and on the hereditary character of this disease. The mystery remains concerning the mechanism of the favourable effect in clomifene resistant PCOS, of surgical and laparoscopic methods of ovulation induction to which it may be useful to resort after mature consideration. More recently the benefit at the administration of metformine has been confirmed by several works.

[Effect of combined conjugated estrogen-medrogestone replacement therapy on lipid profiles, climacteric symptoms and the endometrium]. / Effets sur les lipides, les symptômes climatériques et l'endomètre d'une association d'estrogènes conjugués et de médrogestone dans le traitement hormonal substitutif.

OBJECTIVE: To assess the effects of continuous administration of conjugated estrogen combined with sequential administration of medrogestone on lipid profiles, climateric symptoms and endometrial tolerance. METHODS: This multicenter open study was conducted for one year to assess the effects of a hormone replacement therapy (HRT) regimen using Premarin (0.625 mg/day 28d/28) combined with medrogestone 5mg for 12 days (d17-d28 of each 28-day cycle) on lipid profiles, climateric symptoms and cycle control in 228 post menopausal women with an intact uterus. The subjects were recruited in 23 centers in 7 countries in Europe and Asia. Serum lipid/lipoprotein levels were determined at baseline and at cycles 3, 6, 13; endometrium biopsies were performed at screening then at cycle 13. Climateric symptoms and bleeding patterns were recorded by the patients from daily diaries cards collected at baseline and at visits during cycle 3, 6, 9, and 13. RESULTS: By cycle 3, the conjugated estrogen-medrogestone combination induced significant modifications of the lipid profile which were judged favorable. These modifications were maintained throughout treatment. All the baseline values were within normal limits. Mean variations compared with baseline values (expressed in mmol/l) after cycles 3, 6, and 13 were -0.46, -0.54, and -0.46 for total cholesterol (p<0.05), + 0.053, + 0.057, and + 0.078 for HDL-cholesterol (p<0.05) and -0.556, -0. 542, and -0.493 for LDL-cholesterol (p<0.001) respectively. VLDL-cholesterol levels were unchanged. Triglycerides increased significantly though moderately: + 0.12, + 0.15, and + 0.15 mmol/l at cycles 3, 6, and 13 respectively. Endometrial biopsies obtained at cycle 13 (n=195) did not reveal any endometrial hyperplasia. Withdrowal bleeding was predictable for a 6 to 7.4 day interval. The incidence of irregular bleeding varied from 7 to 33% and decreased progressively over the 13-cycle treatment. The incidence of amenorrhea increased from 14 to 52% over the 12 months studied. Finally, at each cycle, menopausal symptoms (mean number of hot flushes/day and Küpperman score) were significantly improved compared with the baseline. As expected, modifications were more pronounced after cycle 1, but improvements were maintained throughout the study. CONCLUSION: Continuous administration of Premarin in combination with sequential administration of medrogestone was found to be an effective treatment for menopausal symptoms. It was associated with favorable modifications of the lipid profile and was safe for the endometrium.