Search Results

You are looking at 1 - 9 of 9 items for

  • Author: Anne Bachelot x
Clear All Modify Search
Free access

Julie Sarfati, Anne Bachelot, Christiane Coussieu, Géri Meduri and Philippe Touraine

Objective

Evaluation of postmenopausal women with suspicion of androgen-secreting tumor.

Design and patients

We retrospectively studied 22 postmenopausal women referred to our center for suspicion of androgen-secreting tumor. All patients had clinical, biological, and morphological evaluation. In absence of adrenal tumors, ovarian surgery was most often proposed and immunohistochemistry (IHC) studies were performed.

Results

Ovarian tumors were detected by ultrasound and/or magnetic resonance imaging in eight patients. Two adrenal androgen-secreting tumors were diagnosed by an adrenal computed tomography (CT) scan. The clinical presentation of the women with or without tumors was similar. Nevertheless, women with tumor exhibited significantly higher testosterone levels and lower basal FSH and LH levels than the other women (2.6±2.7 vs 0.9±0.9 ng/ml, P<0.05; 26.5±22.9 vs 66.5±26.0 IU/l, P<0.01; and 12.0±8.6 vs 24.1±8.9 IU/l, P<0.05 respectively). Based on a likelihood ratio test, patients with a tumor had 8.4 and 10.8 times higher risk of having a testosterone level ≥1.4 ng/ml or an FSH level ≤35 IU/l. Finally, IHC analysis with an anti-P450c17α antibody allowed the identification of an elevated number of ovarian androgen-producing cells in five patients in whom no tumor was found.

Conclusions

Androgen-secreting tumors are clinically difficult to discriminate from other causes of postmenopausal hyperandrogenism. Testosterone and FSH were the two discriminative markers in a multivariate analysis. Ovarian and adrenal tumors were detected by imaging studies. However, ovarian non-tumoral causes of hyperandrogenism may be difficult to detect with conventional histology.

Free access

Anne Bachelot, Virginie Grouthier, Carine Courtillot, Jérôme Dulon and Philippe Touraine

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

Free access

Anne Bachelot, Zeina Chakhtoura, Geneviève Plu-Bureau, Mathieu Coudert, Christiane Coussieu, Yasmina Badachi, Jérome Dulon, Beny Charbit and Philippe Touraine

The journal apologises for an error in the Funding section of the above article published in the October issue of the journal (vol 167 issue 4 pages 499–505). The corrected section is published in full below:

Free access

Anne Bachelot, Zeina Chakhtoura, Geneviève Plu-Bureau, Mathieu Coudert, Christiane Coussieu, Yasmina Badachi, Jérome Dulon, Beny Charbit and Philippe Touraine

Objective

Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility.

Design

Case/control study.

Methods

Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28±3 days), were included. LH pulse patterns over 6 h were determined in patients and controls.

Results

No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels.

Conclusions

LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

Free access

Anne Bachelot, Jean Louis Golmard, Jérôme Dulon, Nora Dahmoune, Monique Leban, Claire Bouvattier, Sylvie Cabrol, Juliane Leger, Michel Polak and Philippe Touraine

Aim

Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are frequent. The determinants of them have not yet been established.

Objective

To establish the prevalence of adverse outcomes and to find determining factors for each of them.

Design, patients, and methods

Cross-sectional monocentric study of 104 patients with childhood onset of CAH (71 women, 33 men). Analysis established first the determinants of clinical, hormonal, genetic variables and second a composite criterion for some of the outcomes and determinants.

Results

BMI was above 25 kg/m2 in 44% of the cohort, adrenal hyperplasia and/or nodules were present in 45% of the patients, and irregular menstrual cycles and hyperandrogenism were found in 50 and 35% of the women respectively. In univariate analysis, the determinants of these outcomes were all linked to disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione concentrations. Low weight was a determinant of abnormal bone mineral density (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36% of the men). Total cumulative glucocorticoid dose was a determinant of BMI and TART, whereas fludrocortisone dose was a determinant of TART (P=0.03). In men, the composite criterion was associated with androstenedione concentration and CF. In women, the composite criterion was associated with total testosterone concentration.

Conclusion

The present study confirms the high prevalence of adverse outcomes in CAH patients. These are, most often, related to disease control. The impaired health status of adults with CAH could therefore be improved through the modification of treatment.

Free access

Paul Laissue, Sophie Christin-Maitre, Philippe Touraine, Frederique Kuttenn, Olli Ritvos, Kristiina Aittomaki, Nathalie Bourcigaux, Laetitia Jacquesson, Philippe Bouchard, Rene Frydman, Didier Dewailly, Anne-Céline Reyss, Luke Jeffery, Anne Bachelot, Nathalie Massin, Marc Fellous and Reiner A Veitia

Background and objective: Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF).

Subject and methods: We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child.

Results: We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions.

Conclusions: We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.

Free access

Sylvie Salenave, Valérie Bernard, Christine Do Cao, Laurence Guignat, Anne Bachelot, Sophie Leboulleux, Céline Droumaguet, Hélène Bry-Gauillard, Peggy Pierre, Lise Crinière, Pietro Santulli, Philippe Touraine, Philippe Chanson, Martin Schlumberger, Dominique Maiter, Eric Baudin and Jacques Young

Context

Mitotane is an adrenolytic and anticortisolic drug used in adrenocortical carcinoma (ACC), Cushing's disease (CD), and ectopic ACTH syndrome. Its effects on the ovaries are unknown.

Objective

To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women.

Patients

We studied 21 premenopausal women (ACC: n=13; CD: n=8; median age 33 years, range 18–45 years) receiving mitotane at a median initial dose of 3 g/day (range 1.5–6 g/day).

Methods

Gynecological history was collected and ovarian ultrasound was performed. Four women also underwent ovarian CT or magnetic resonance imaging. Serum gonadotropin, estradiol (E2), androgens, sex hormone-binding globulin (SHBG), and circulating mitotane levels were determined at diagnosis and during mitotane therapy.

Results

In the women included, ovarian macrocysts (bilateral in 51%) were detected after a median 11 months (range: 3–36) of mitotane exposure. The median number of macrocysts per woman was two (range: 1–4) and the median diameter of the largest cysts was 50 mm (range: 26–90). Menstrual irregularities and/or pelvic pain were present in 15 out of 21 women at macrocyst diagnosis. In two women, the macrocysts were revealed by complications (ovarian torsion and hemorrhagic macrocyst rupture) that required surgery. Mitotane therapy was associated with a significant decrease in androstenedione and testosterone levels and a significant increase in LH levels. Serum FSH and E2 levels were also increased, and SHBG levels rose markedly.

Conclusions

Mitotane therapy causes significant morphological and ovarian/gonadotrope hormonal abnormalities in premenopausal women. Follicular thecal steroid synthesis appears to be specifically altered and the subsequent increase in gonadotropins might explain the development of macrocysts. The mechanisms underlying these adverse effects, whose exact prevalence in this population still needs to be determined, are discussed.

Free access

Zeina Chakhtoura, Anne Bachelot, Dinane Samara-Boustani, Jean-Charles Ruiz, Bruno Donadille, Jérôme Dulon, Sophie Christin-Maître, Claire Bouvattier, Marie-Charles Raux-Demay, Philippe Bouchard, Jean-Claude Carel, Juliane Leger, Frédérique Kuttenn, Michel Polak and Philippe Touraine

Objective

It remains controversial whether long-term glucocorticoids are charged of bone demineralization in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to know whether cumulative glucocorticoid dose from the diagnosis in childhood to adulthood in patients with CAH had a negative impact on bone mineral density (BMD).

Design

This was a retrospective study.

Methods

Thirty-eight adult patients with classical and non-classical CAH were included. BMD was measured in the lumbar spine and femoral neck. Total cumulative glucocorticoid (TCG) and total average glucocorticoid (TAG) doses were calculated from pediatric and adult files.

Results

We showed a difference between final and target heights (−0.82±0.92 s.d. for women and −1.31±0.84 s.d. for men; P<0.001). Seventeen patients (44.7%) had bone demineralization (35.7% of women and 70% of men). The 28 women had higher BMD than the 10 men for lumbar (−0.26±1.20 vs −1.25±1.33 s.d.; P=0.02) and femoral T-scores (0.21±1.30 s.d. versus −1.08±1.10 s.d.; P=0.007). In the salt-wasting group, women were almost significantly endowed with a better BMD than men (P=0.053). We found negative effects of TCG, TAG on lumbar (P<0.001, P=0.002) and femoral T-scores (P=0.006, P<0.001), predominantly during puberty. BMI was protective on BMD (P=0.006).

Conclusion

The TCG is an important factor especially during puberty for a bone demineralization in patients with 21-hydroxylase deficiency. The glucocorticoid treatment should be adapted particularly at this life period and preventive measures should be discussed in order to limit this effect.

Free access

Anne Bachelot, Agnès Rouxel, Nathalie Massin, Jérome Dulon, Carine Courtillot, Christine Matuchansky, Yasmina Badachi, Anne Fortin, Bernard Paniel, Fabrice Lecuru, Marie-Aude Lefrère-Belda, Elisabeth Constancis, Elisabeth Thibault, Géri Meduri, Anne Guiochon-Mantel, Micheline Misrahi, Frédérique Kuttenn, Philippe Touraine and on behalf of the POF-GIS Study Group

Objective

Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis.

Design and methods

We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center.

Results

Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1.

Conclusion

A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.