Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol.

PURPOSE: To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS). METHODS: We enrolled 48 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. These patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We analyzed pre-treatment and post-treatment BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, DHEA-S, Δ-4-androstenedione, SHBG, prolactin, glucose/IRI ratio, HOMA index, and resumption of regular menstrual cycles. RESULTS: We evidenced a statistically significant reduction of systolic blood pressure, Ferriman-Gallwey score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin, and HOMA Index; in the same patients, we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (62.5%; p < 0.05) post-treatment menstrual cycle regularization. CONCLUSIONS: D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.

Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS.

Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

Ovarian steroid cell tumor, not otherwise specified, producing testosterone.

Steroid cell tumor, not otherwise specified, is a rare type of ovarian sex cord-stromal tumor with malignant potential. Some of these tumors produce testosterone. We describe a case of steroid cell tumor of the ovary associated with virilization. A 23-year-old nulliparous woman was found to have an ovarian tumor when she visited her primary doctor for virilization and oligomenorrhea. Magnetic resonance imaging revealed a solid left ovarian tumor 40 mm in size. Her laboratory data revealed elevated testosterone with normal levels of gonadotropins, estradiol, dehydroepiandrosterone sulfate and cortisol. She underwent left adnexectomy. On histopathologic and immunohistochemical analyses, the tumor was diagnosed as steroid cell tumor, not otherwise specified, without malignant behavior. After removal of the tumor, serum testosterone level decreased, and there have been no signs of recurrence.

Menstrual characteristics of secondary school girls in Ibadan, Nigeria.

BACKGROUND: Disturbances of menstrual function are the commonest complaints among adolescents. Disorders of menstruation may have implications for future reproductive health. OBJECTIVE: To assess menstrual patterns among school girls in Ibadan, south-western Nigeria. METHODS: This was cross-sectional descriptive study in which 1,213 apparently healthy school girls were selected by multistage sampling technique in fifteen secondary schools from the five local governments within the metropolis. Information about details of menstrual experience was obtained with a self-administered questionnaire. RESULTS: The girls were aged between 9 and 23 years. Majority of respondents 768 (633%) experienced normal cycle length, 391 (32.2%) had short cycles; and 55 (4.5%) had cycle length greater than 35 days. Prevalence of normal cycles increased with increasing age; abnormalities of cycle length tended to decrease with increasing age (p < 0.01). The majority, 1,152 (95%), had normal menstrual loss. The majority 882 (72.7%) experienced dysmenorrhoea; severe dysmenorrhoea was reported by 154 (12.7%). Cycle length was not associated with presence of dysmenorrhoea (p > 0.05); 695 (57.3%) had symptoms of pre-menstrual syndrome. CONCLUSION: Prevalence of menstrual abnormalities among adolescent schoolgirls is high. More attention should be paid to identify and treat these menstrual morbidities.

The impact of bariatric surgery on menstrual patterns.

BACKGROUND: Obesity and anovulation are common medical problems in the United States. Anovulation in obese patients primarily manifests with irregular, sporadic or absent menstrual bleeding. Weight loss of at least 5% has been shown to reverse obesity-related anovulation. The aim of this study was to assess the impact of bariatric surgery on infertility in morbidly obese women and to identify factors associated with return of normal menses following bariatric surgery. METHODS: A survey of patients was collected from the bariatric surgery data-base at the Hospital of the University of Pennsylvania. 410 women under the age of 40 were sent questionnaires. 195 patients completed the questionnaire, and 29 patients had incorrect addresses without a forwarding address, resulting in a 51.2% response rate. Patients who reported menstrual cycle lengths >35 days were considered abnormal. 92 of the 195 responders were considered anovulatory preoperatively, based on menstrual history. RESULTS: There was no significant difference in postoperative BMI, BMI decrease or age at surgery between the survey responders and non-responders. There was a significant difference between these 2 groups in time since surgery (P=.01). Both groups had a decrease in BMI of >18 kg/m(2). The mean menstrual cycle length preoperatively among those categorized as ovulatory and anovulatory was 27.3 and 127.5 days, respectively. Of the 98 patients who were anovulatory preoperatively, 70 patients (71.4%) regained normal menstrual cycles after surgery. Those patients who regained ovulation had greater weight loss than those who remained anovulatory (61.4 kg vs 49.9 kg, P=0.02). CONCLUSIONS: Anovulation resulting in abnormal menses is a common problem in morbidly obese premenopausal women. The menstrual cycle disorders may completely resolve after bariatric surgery. Thus, infertility due to anovulation among morbidly obese women could potentially be viewed as an additional indication for bariatric surgery.

Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

CONTEXT: Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. DESIGN: This was a randomized, open-label study over 7 yr. SETTING: The study was conducted at a university hospital. PATIENTS: Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. INTERVENTION: Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). MAIN OUTCOME MEASURES: Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). RESULTS: None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. CONCLUSIONS: In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

Does weight-bearing exercise protect against the effects of exercise-induced oligomenorrhea on bone density?

Does weight-bearing exercise offset bone loss associated with oligomenorrhea? If so, bone mineral density (BMD) will be stable at weight bearing sites but decrease at non-weight-bearing sites with increasing duration of oligomenorrhea. To test this hypothesis, BMD (g/cm2), was measured by dual-energy X-ray absorptiometry in 41 oligomenorrheic ballet dancers aged 17.7 +/- 0.2 years (mean +/- SEM) and 46 age-matched controls with normal menstrual function. BMD correlated negatively with the duration of oligomenorrhea at weight-bearing and non-weight-bearing sites (femoral neck, r = -0.33, p < 0.05; Ward's triangle, r = -0.29, p = 0.06; trochanter, r = -0.33, p < 0.05; lumber spine, r = -0.25, p = 0.1; skull, r = -0.29, p = 0.06; arms, r = -0.32, p < 0.05; ribs, r = -0.30, p = 0.06). The slopes of the regression of BMD on duration of oligomenorrhea were greater at the proximal femur (trochanter, -0.28 +/- 0.13, femoral neck, -0.24 +/- 0.11; Ward's triangle, -0.29 +/- 0.15) than the skull (-0.15 +/- 0.08, p < 0.05, p < 0.1, p < 0.1 respectively). The slopes at the trochanter and femoral neck were also greater than at the ribs (-0.10 +/- 0.05; both p < 0.1). In the dancers with oligomenorrhea of less than 40 months duration, BMD was higher than the age-predicted mean at weight-bearing sites (except the lumber spine), but not at non-weight-bearing sites (femoral neck, 9.1 +/- 3.4%; Ward's triangle, 10.0 +/- 1.7%; trochanter, 9.4 +/- 4.1%, all p < 0.05; lumbar spine, -2.1 +/- 2.7%, NS; skull, -2.5 +/- 2.1%, NS; ribs, -3.0 +/- 1.6% NS; arms, -3.9 +/- 1.6%; p < 0.05). In the dancers with greater than 40 months oligomenorrhea, BMD was no higher than the age predicted mean, at the weight bearing sites, and was lower at non-weight bearing sites (femoral neck, 4.3 +/- 2.3%, NS; Ward's triangle, 3.5 +/- 3.2%, NS; trochanter, 2.1 +/- 2.7%, NS; lumbar spine, -3.8 +/- 2.1%, NS; arms, -7.5 +/- 0.8%, p < 0.05; skull, -6.2 +/- 1.8%, p < 0.01; ribs, -5.4 +/- 1.1%, p < 0.0001). In conclusion, weight-bearing exercise is unlikely to offset the deleterious effects of oligomenorrhea. Bone loss appears to occur at all sites but may begin from a higher level at weight-bearing sites and may proceed more rapidly.