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Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels

Els Elaut — 2008-02-26T17:02:12-00:00

Eur J Endocrinol, Vol. 158, No. 3. (1 March 2008), pp. 393-399.

ObjectiveAn unknown proportion of transsexual women (defined as post-operative male-to-female transsexuals on oestrogen replacement) experience hypoactive sexual desire disorder (HSDD). It has been suggested that the absence of ovarian androgen production together with oestrogen treatment-related increase in sex hormone-binding globulin (SHBG) levels could be leading to HSDD, due to low levels of biologically available testosterone. This study wishes to document the HSDD prevalence among transsexual women and the possible association to androgen levels. DesignCross-sectional study. MethodsTranssexual women (n=62) and a control group of ovulating women (n=30) participated in this study. Questionnaires measuring sexual desire (sexual desire inventory) and relationship and sexual satisfaction (Maudsley Marital Questionnaire) were completed. Serum levels of total testosterone, LH and SHBG were measured in blood samples obtained at random in transsexual women and in the early follicular phase in ovulating women. ResultsThe transsexual group had lower levels of total and calculated free testosterone (both P<0.001) than the ovulating women. HSDD was reported in 34% of the transsexual and 23% of the ovulating women (P=0.30). Both groups reported similar levels of sexual desire (P=0.97). For transsexual women, no significant correlation was found between sexual desire and total (P=0.64) or free testosterone (P=0.82). In ovulating women, these correlations were significant (P=0.006, resp. P=0.003). ConclusionsHSDD is reported in one-third of transsexual women. This prevalence is not substantially different from controls, despite markedly lower (free) testosterone levels, which argues against a major role of testosterone in this specific group. 10.1530/EJE-07-0511

Androgen Deficiency in Women

Karen Miller — 2008-02-15T16:42:38-00:00

J Clin Endocrinol Metab, Vol. 86, No. 6. (1 June 2001), pp. 2395-2401.

Physiological and pathological processes as well as iatrogenic interventions may result in androgen deficiency compared with levels in young healthy women. Whether relative androgen deficiency results in a clinical syndrome similar to that reported in men, including osteopenia, increased fat mass, decreased libido, and diminished quality of life, has not been definitively established. However, preliminary data in postmenopausal women suggest that physiological androgen replacement therapy, which involves substantially lower doses than those used in men, may result in increased bone mineral density, increased libido, and improved quality of life. The safety of androgen preparations that result in supraphysiological levels has not been established in women and would be expected to result in hirsutism, acne, and virilization with chronic use. Androgen preparations that avoid liver metabolism and result in physiological serum androgen levels in women with androgen deficiency are not currently available, but are in development. Therefore, although widespread screening and hormone replacement for androgen deficiency cannot be recommended yet, increasing interest in this topic makes consideration of the available data important. 10.1210/jc.86.6.2395

Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial

Eleanor Gurnell — 2008-02-09T17:47:52-00:00

J Clin Endocrinol Metab, Vol. 93, No. 2. (1 February 2008), pp. 400-409.

Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison's disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects. Conclusion: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison's disease. 10.1210/jc.2007-1134

Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease.

JF Reckelhoff — 2008-01-28T17:07:26-00:00

Am J Physiol Renal Physiol, Vol. 289, No. 5. (November 2005)

Treatment of aging men and women with testosterone supplements is increasing. The supplements are given to postmenopausal women mainly to improve their libido and to aging men to improve muscle mass and bone strength, to improve libido and quality of life, to prevent and treat osteoporosis, and, with the phosphodiesterase-5 inhibitors, such as sildenafil, to treat erectile dysfunction. The increased use of testosterone supplements in aging individuals has occurred despite the fact that there have been no rigorous clinical trials examining the effects of chronic testosterone on the cardiovascular-renal disease risk. Studies in humans and animals have suggested that androgens can increase blood pressure and compromise renal function. Androgens have been shown to increase tubular sodium and water reabsorption and activate various vasoconstrictor systems in the kidney, such as the renin-angiotensin system and endothelin. There is also evidence that androgens may increase oxidative stress. Furthermore, the kidney contains the enzymes necessary to produce androgens de novo. This review presents an overview of the data from human and animal studies in which the role of androgens in promoting renal and cardiovascular diseases has been investigated.

The Age-Associated Decline of Androgens in Reproductive Age and Menopausal Black and White Women

Jessica Spencer — 2008-01-12T19:08:17-00:00

J Clin Endocrinol Metab, Vol. 92, No. 12. (1 December 2007), pp. 4730-4733.

Context: The effect of race and obesity on the age-associated decline of androgens in reproductive-aged and menopausal women has not been well characterized. Objective: Our objective was to determine the impact of racial differences and body mass index (BMI) on the change in androgen levels during a woman's reproductive and early menopausal years. Design and Setting: We conducted a frequency-matched cross-sectional study at a tertiary academic medical center. Patients or Other Participants: Subjects included 260 healthy, nonhirsute and eumenorrheic, self-identified Black and White women, ages 1560 yr. Interventions: A medical and reproductive history, physical exam, and blood sampling were determined in the fasting state during the early follicular phase. Main Outcome Measures: Serum levels of androgens or androgen metabolites (dehydroepiandrosterone sulfate, androstenedione, and total and free testosterone) and SHBG were measured and the BMI, the waist-to-hip ratio (WHR), and the basal insulin resistance estimated by the homeostasis model assessment for insulin resistance determined. Results: After controlling for differences in BMI, insulin resistance, and WHR, Black women had lower androgen levels than age-matched White women. All androgens, or androgen metabolites, declined similarly across the reproductive lifespan and menopausal transition in both Black and White women. Race was a significant predictor of dehydroepiandrosterone sulfate, androstenedione, and total and free testosterone but not SHBG. Conclusions: Eumenorrheic, nonhirsute Black women have a lower range of normal androgen levels than White women of the same age, BMI, WHR, and homeostasis model assessment index for insulin resistance. Race and age-adjusted data should be considered when evaluating androgen levels in women between the ages of 15 and 60 yr. 10.1210/jc.2006-2365

Association of SHBG gene polymorphism with menarche.

N Xita — 2008-01-11T17:11:45-00:00

Mol Hum Reprod, Vol. 11, No. 6. (June 2005), pp. 459-462.

The age of menarche may be subject to hereditary influences but the specific determinants are unknown. Our aim was to investigate the possible association of a functional (TAAAA)n polymorphism in the promoter of the sex hormone-binding globulin (SHBG) gene with the timing of menarche. This polymorphism has been associated with polycystic ovary syndrome (PCOS) and is considered to contribute to SHBG levels. We studied 130 healthy normal-weight adolescent females from a closed community in North-Western Greece. Information on menarche was obtained through interviews. The BMI was recorded. Genomic DNA was isolated from peripheral blood leukocytes for genotyping the TAAAA repeat region. We subdivided our subjects into two groups based on median age of menarche: those with menarche <13 years and those with menarche > or =13 years. Genotype analysis revealed six (TAAAA)n alleles containing 5-10 TAAAA repeats. The distribution of alleles was different in the two groups. Girls with late menarche had more frequently longer TAAAA alleles (>8 repeats), while girls with early menarche had shorter alleles at a greater frequency (P=0.048). The major contribution to early menarche was by the 6 TAAAA repeat allele. Furthermore, carriers of the longer allele genotypes had later menarche (13.24+/-1.15 years) than those with shorter allele genotypes (12.67+/-1.15, P=0.018). These findings provide evidence for a genetic contribution of SHBG gene to the age of menarche.

Sex hormone-binding globulin is synthesized in target cells

SM Kahn — 2008-01-11T16:35:12-00:00

J Endocrinol, Vol. 175, No. 1. (1 October 2002), pp. 113-120.

Sex hormone-binding globulin (SHBG) is a multifunctional protein that acts in humans to regulate the response to steroids at several junctures. It was originally described as a hepatically secreted protein that is the major binding protein for sex steroids in plasma, thereby regulating the availability of free steroids to hormone-responsive tissues. SHBG also functions as part of a novel steroid-signaling system that is independent of the classical intracellular steroid receptors. Unlike the intracellular steroid receptors that are ligand-activated transcription factors, SHBG mediates androgen and estrogen signaling at the cell membrane by way of cAMP. We have reviewed the current state of knowledge on the SHBG gene and the role of SHBG in steroid signaling (we shall not address its function as a plasma-binding protein). 10.1677/joe.0.1750113

Polycystic Ovaries in Nonobese Adolescents and Young Women with Ovarian Androgen Excess: Relation to Prenatal Growth

Lourdes Ibanez — 2008-01-11T00:39:38-00:00

J Clin Endocrinol Metab, Vol. 93, No. 1. (1 January 2008), pp. 196-199.

Objective: Reduced growth before birth is known to associate with a smaller ovarian volume in adolescents and women without androgen excess. We studied whether prenatal growth relates also to ovarian size and polycystic ovary (PCO) morphology in nonobese adolescents and young women with ovarian androgen excess. Design: A cross-sectional analysis of standardized case notes over a 2-yr period was performed. Patients: Nonobese adolescents and young women (age [~]17 yr; n = 86) seen for ovarian androgen excess, as confirmed by 17-hydroxy-progesterone hyperresponse to a GnRH agonist, were included in the study. Measurements: Endocrine-metabolic assessment in fasting state, together with a vaginal ultrasound scan to verify the presence or absence of PCO was performed. Birth weight and gestational age were derived from medical records. Results: PCO prevalence by ultrasound was 38%. Absence of PCO was associated with a shift (P < 0.0005) of the birth weight distribution toward lower values. Patients with a birth weight less than 3.0 kg were 6-fold more likely to have no PCO than to have PCO. Birth weight was across a wide range (1.54.0 kg) associated with ovarian volume in hyperandrogenic patients with noncystic ovaries (r = 0.60; P < 0.00001) and was, in a multiple regression analysis, the prime variable linked to ovarian volume ( = 0.57; P < 0.00001), explaining 32% of its variance. Conclusions: The ovarian size and the development of a PCO morphology in nonobese adolescents and young women with ovarian androgen excess relate to prenatal growth. These findings indicate that there are two subgroups of nonobese patients with ovarian androgen excess: one with a normal birth weight distribution and with PCO, and one with lower birth weights and without PCO. 10.1210/jc.2007-1800

Long-Term Observation of 87 Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogs: Impact on Adult Height, Body Mass Index, Bone Mineral Content, and Reproductive Function

Anna Pasquino — 2008-01-11T00:37:10-00:00

J Clin Endocrinol Metab, Vol. 93, No. 1. (1 January 2008), pp. 190-195.

Objective: We assessed in a retrospective unicenter study the impact of treatment with GnRH analogs (GnRHa) on adult height (AH), body mass index (BMI), bone mineral density (BMD), and reproductive function in girls with idiopathic central precocious puberty (ICPP). Patients: Eighty-seven ICPP patients were treated with GnRHa for 4.2 +/- 1.6 yr (range 37.9) and observed for 9.9 +/- 2.0 yr (range 410.6 yr) after discontinuation of treatment; to estimate the efficacy better, 32 comparable ICPP untreated girls were analyzed. Results: AH was 159.8 +/- 5.3 cm, significantly higher than pretreatment predicted AH (PAH) either for accelerated or for average tables of Bayley and Pinneau. The gain in centimeters between pretreatment PAH and AH was 5.1 +/- 4.5 and 9.5 +/- 4.6 cm, respectively. Hormonal values and ovarian and uterine dimensions, reduced during treatment, increased to normal after 1 yr without therapy. Age of menarche was 13.6 +/- 1.1 yr with an interval of 0.9 +/- 0.4 yr after therapy. Menstrual pattern was normal. Six girls became pregnant and delivered normal offspring. BMI SD score for chronological age increased, but not significantly, before, during, and after therapy. BMD at discontinuation of treatment was significantly lower and increased to control values after gonadal activity resumption. Conclusions: GnRHa treatment in ICPP is safe for the reproductive system, BMD, and BMI and helpful in reaching AH close to target height; however, the variability of individual responses suggests that one choose more parameters than increment in height, especially in girls with pubertal onset over 8 yr of age. 10.1210/jc.2007-1216

Long-Term Treatment of Transsexuals with Cross-Sex Hormones: Extensive Personal Experience

Louis Gooren — 2008-01-10T23:06:06-00:00

J Clin Endocrinol Metab, Vol. 93, No. 1. (1 January 2008), pp. 19-25.

Context: Transsexuals receive cross-sex hormone treatment. Its short-term use appears reasonably safe. Little is known about its long-term use. This report offers some perspectives. Setting: The setting was a university hospital serving as the national referral center for The Netherlands (16 million people). Patients: From the start of the gender clinic in 1975 up to 2006, 2236 male-to-female and 876 female-to-male transsexuals have received cross-sex hormone treatment. In principle, subjects are followed up lifelong. Interventions: Male-to-female transsexuals receive treatment with the antiandrogen cyproterone acetate 100 mg/d plus estrogens (previously 100 microg ethinyl estradiol, now 24 mg oral estradiol valerate/d or 100 microg transdermal estradiol/d). Female-to-male transsexuals receive parenteral testosterone esters 250 mg/2 wk. After 1836 months, surgical sex reassignment including gonadectomy follows, inducing a profound hypogonadal state. Main Outcome Measures: Outcome measures included morbidity and mortality data and data assessing risks of osteoporosis and cardiovascular disease. Results: Mortality was not higher than in a comparison group. Regarding morbidity, with ethinyl estradiol, there was a 68% incidence of venous thrombosis, which is no longer the case with use of other types of estrogens. Continuous use of cross-sex hormones is required to prevent osteoporosis. Androgen deprivation plus an estrogen milieu in male-to-female transsexuals has a larger deleterious effect on cardiovascular risk factors than inducing an androgenic milieu in female-to-male transsexuals, but there is so far no elevated cardiovascular morbidity/mortality. Low numbers of endocrine-related cancers have been observed in male-to-female transsexuals. Conclusions: Cross-sex hormone treatment of transsexuals seems acceptably safe over the short and medium term, but solid clinical data are lacking. 10.1210/jc.2007-1809

Metformin for the treatment of the polycystic ovary syndrome.

JE Nestler — 2008-01-09T03:27:35-00:00

N Engl J Med, Vol. 358, No. 1. (3 January 2008), pp. 47-54.

Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study.

P Feuillan — 2008-01-08T19:10:07-00:00

J Clin Endocrinol Metab, Vol. 92, No. 6. (June 2007), pp. 2100-2106.

CONTEXT: Girls with McCune-Albright syndrome (MAS) and related disorders have gonadotropin-independent precocious puberty due to estrogen secretion from ovarian cysts. Their puberty does not respond to GnRH agonist therapy, and short-acting aromatase inhibitors have had limited effectiveness. OBJECTIVE: Our objective was to assess the effectiveness of the potent, third-generation aromatase inhibitor letrozole in decreasing pubertal progression in girls with MAS and to assess the response of indices of bone turnover associated with the patients' polyostotic fibrous dysplasia. DESIGN: Subjects were evaluated at baseline and every 6 months for 12-36 months while on treatment with letrozole 1.5-2.0 mg/m(2).d. SETTING: This was an open-label therapeutic trial at a single clinical center. PATIENTS: Patients included nine girls aged 3-8 yr with MAS and/or gonadotropin-independent puberty. MAIN OUTCOME MEASURES: Measures included rates of linear growth, bone age advance, mean ovarian volume, estradiol, episodes of vaginal bleeding, and levels of the indices of bone metabolism: serum osteocalcin, alkaline phosphatase, urinary hydroxyproline, pyridinoline, deoxypyridinoline, and N-telopeptides. RESULTS: Girls had decreased rates of growth (P < or = 0.01) and bone age advance (P < or = 0.004) and cessation or slowing in their rates of bleeding over 12-36 months of therapy. Mean ovarian volume, estradiol, and indices of bone metabolism fell after 6 months (P < or = 0.05) but tended to rise by 24-36 months. Uterine volumes did not change. One girl had a ruptured ovarian cyst after 2 yr of treatment. CONCLUSIONS: This preliminary study suggests that letrozole may be effective therapy in some girls with MAS and/or gonadotropin-independent precocious puberty. Possible adverse effects include ovarian enlargement and cyst formation.

Growth hormone treatment and left ventricular dimensions in Turner syndrome.

LA Matura — 2008-01-08T00:29:24-00:00

J Pediatr, Vol. 150, No. 6. (June 2007), pp. 587-591.

OBJECTIVE: To determine whether cardiac dimensions were different in girls with Turner syndrome (TS) who received growth hormone (GH) compared with those who did not receive GH. STUDY DESIGN: This retrospective, cross-sectional study analyzed echocardiograms in 86 females with TS divided into GH-treated (n = 67) and untreated (n = 19) groups. The subjects all participated in the National Institutes of Health protocol between 2001 and 2006. RESULTS: The average age was 16.2 years (range, 10 to 25 years), and average duration of GH treatment was 4.4 years (range, 1 to 14 years). The GH-treated group was taller by approximately 7 cm (P = .004), but cardiac dimensions normalized to body surface area (BSA), including septal and posterior wall thickness and left ventricular (LV) mass and internal diameters, did not differ significantly between the 2 groups. The fractional shortening index was similar in the 2 groups. Multiple regression analyses indicated that BSA, but not duration of GH treatment, predicted LV dimensions in girls with TS. CONCLUSIONS: GH treatment of girls with TS increases stature but does not disproportionately affect cardiac dimensions.

Estrogen therapy and coronary-artery calcification.

JE Manson — 2008-01-07T22:28:18-00:00

N Engl J Med, Vol. 356, No. 25. (21 June 2007), pp. 2591-2602.

BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.)