Courtney A. Marsh

Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis.

STUDY OBJECTIVE Adult women with endometriosis are often diagnosed with comorbid pain, mood, and autoimmune conditions. This study aims to describe the occurrence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis evaluated at our medical center. DESIGN Retrospective review of medical records. SETTING Department of Obstetrics and Gynecology at a tertiary referral center. PARTICIPANTS 138 adolescents/young women who were less than age 24 years at the time of their initial visit at our medical center, and whose surgical diagnosis of endometriosis was made at our institution or by outside institutions by the age of 21. INTERVENTIONS None. MAIN OUTCOME MEASURES Prevalence of comorbid pain syndromes (defined as interstitial cystitis, irritable bowel syndrome, chronic headaches, chronic low back pain, vulvodynia, fibromyalgia, temporomandibular joint disease, and chronic fatigue syndrome), mood conditions (defined as depression and anxiety), and asthma. RESULTS Comorbid pain syndromes were found in 77 (56%) women, mood conditions in 66 (48%) women, and asthma in 31 (26%) women. Comparing endometriosis patients with and without comorbid pain syndromes, no differences were found in age at time of diagnosis, endometriosis symptoms, and endometriosis stage. Patients with comorbid pain syndromes were more likely to report mood conditions (62% vs 30% respectively, P < .001) and smoking (31% vs 10% respectively, P = .003), underwent more surgeries for endometriosis (median of 2 [range, 1-7] vs 1 [range, 1-5], P < .005), and were more likely to undergo appendectomy or cholecystectomy (30% vs 13%, P = .02). CONCLUSIONS Comorbid pain syndromes, mood conditions and asthma are common in adolescents and young women with endometriosis.

Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study.

OBJECTIVE To evaluate emotional processing in women with insulin-resistant polycystic ovary syndrome (IR-PCOS) and its relationship to glucose regulation and the mu-opioid system. DESIGN Case-control pilot. SETTING Tertiary referring medical center. PATIENT(S) Seven women with IR-PCOS and five non-insulin-resistant controls, aged 21-40 years, recruited from the general population. INTERVENTION(S) Sixteen weeks of metformin (1,500 mg/day) in women with IR-PCOS. MAIN OUTCOME MEASURE(S) Assessment of mood, metabolic function, and neuronal activation during an emotional task using functional magnetic resonance imaging (fMRI), and mu-opioid receptor availability using positive emission tomography (PET). RESULT(S) We found that insulin-resistant PCOS patients [1] had greater limbic activation during an emotion task than controls (n = 5); [2] trended toward decreased positive affect and increased trait anxiety; [3] after metformin treatment, had limbic activation that no longer differed from controls; and [4] had positive correlations between fMRI limbic activation during emotional processing and mu-opioid binding potential. CONCLUSION(S) Patients with IR-PCOS had greater regional activation during an emotion task than the controls, although this resolved with metformin therapy. Alterations in mu-opioid neurotransmission may underlie limbic system activity and mood disorders in IR-PCOS.

Advanced Stage Endometriosis in Adolescents and Young Women

STUDY OBJECTIVE To describe the prevalence and characteristics of advanced stage endometriosis in adolescents and young women treated in a tertiary referral center. DESIGN Retrospective cohort. SETTING Tertiary referral center. PATIENTS AND INTERVENTIONS 86 adolescents and young women (≤22 y) who underwent surgery for endometriosis. The operative reports were reviewed for endometriosis stage, surgical findings, surgical procedures, and pathology. MAIN OUTCOME MEASURES Endometriosis stage reported according to the revised American Fertility Society classification. RESULTS Early stage endometriosis (stage I or II) was found in 66 (76%) and advanced stage endometriosis (stage III or IV) in 20 (23%). The surgical findings in the 20 patients with advanced stage endometriosis included ovarian endometriomas in 14 cases, rectovaginal nodule in 1 case, and diaphragmatic and pulmonary endometriosis in 1 case. Women with advanced stage endometriosis were found to be slightly older at time of diagnosis than those with early stage disease (mean age 20.4 ± 1.4 y vs 18.7 ± 2.2 y respectively, P < .001). CONCLUSION In adolescents and young women with endometriosis, advanced stage disease is not uncommon. The main presentation of advanced stage endometriosis in this age group is ovarian endometriomas rather than extensive peritoneal or adhesive disease.

Surgical Pearls: Laparoscopic Removal of Uterine Remnants in Patients with Mayer-Rokitansky-Küster-Hauser Syndrome

BACKGROUND Females with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome may require surgical removal of uterine remnant(s) which can be accomplished with a laparoscopic approach, described in this case series. CASES Nine females with MRKH and pelvic pain were treated with laparoscopic resection of uterine remnants without major complication. The following management recommendations are offered: (1) preoperative evaluation for urinary tract anomalies and postoperative cystoscopy; (2) medial traction of the remnant to allow adequate exposure of the pelvic sidewall; (3) awareness of possible anomalous vascular supply to uterine remnant; (4) individualized management of associated endometriosis; (5) careful use of surgical terminology, avoiding use of the word hysterectomy. SUMMARY AND CONCLUSION Laparoscopic removal of uterine remnant(s) is safe and effective.

ERα in Tac2 Neurons Regulates Puberty Onset in Female Mice

A variety of data suggest that estrogen action on kisspeptin (Kiss1)-containing arcuate nucleus neurons (which coexpress Kiss1, neurokinin B (the product of Tac2) and dynorphin (KNDy) neurons restrains reproductive onset and function, but roles for estrogen action in these Kiss1 neurons relative to a distinct population of rostral hypothalamic Kiss1 neurons (which does not express Tac2 or dynorphin) have not been directly tested. To test the role for estrogen receptor (ER)α in KNDy cells, we thus generated Tac2(Cre) and Kiss1(Cre) knock-in mice and bred them onto the Esr1(flox) background to ablate ERα specifically in Tac2-expressing cells (ERα(Tac2)KO mice) or all Kiss1 cells (ERα(Kiss1)KO mice), respectively. Most ERα-expressing Tac2 neurons represent KNDy cells. Arcuate nucleus Kiss1 expression was elevated in ERα(Tac2)KO and ERα(Kiss1)KO females independent of gonadal hormones, whereas rostral hypothalamic Kiss1 expression was normal in ERα(Tac2)KO but decreased in ERα(Kiss1)KO females; this suggests that ERα in rostral Kiss1 cells is crucial for control of Kiss1 expression in these cells. Both ERα(Kiss1)KO and ERα(Tac2)KO females displayed early vaginal opening, early and persistent vaginal cornification, increased gonadotropins, uterine hypertrophy, and other evidence of estrogen excess. Thus, deletion of ERα in Tac2 neurons suffices to drive precocious gonadal hyperstimulation, demonstrating that ERα in Tac2 neurons typically restrains pubertal onset and hypothalamic reproductive drive.

Working memory in women with polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in reproductive-age women. Although many studies have focused on the metabolic and reproductive comorbidities associated with PCOS, few have examined brain functioning in this population. In this issue of Fertility and Sterility, Remi Soleman and his team at VU University Medical Center in the Netherlands explored working memory in women with PCOS and the effect of antiandrogen therapy on cognitive function by means of a functional magnetic resonance imaging (fMRI) case-control study (1). This novel approach showed increased activation in brain regions affecting storage of working memory and attentional processes in PCOS women compared with control women. Interestingly, these activation differences resolved with hormonal treatment. The strengths of this study are threefold. First, Soleman et al. used fMRI to evaluate central processing while performing a working memory task. This is superior to previous studies which compared performance on various cognitive tasks before and after antiandrogen therapy (2, 3). Although these studies did suggest that hyperandrogenism associated with PCOS impaired some female-favoring cognitive tasks (such as verbal fluency), other tasks (such as verbal memory, manual dexterity, and visuospatial working memory) did not have consistent results. Because regional activation patterns differ by sex during working memory tasks (4), fMRI is an excellent modality for assessing the effect of androgens on cognitive functioning in women with PCOS. Second, they performed a multivariate regression analysis to correlate serum androgen levels (A, T, and DHEAS) with brain activity in the superior temporal lobe, superior parietal lobe, and inferior parietal lobe. Although they did not find correlation between serum androgen levels and regional activation during the working memory task, the absence of activation differences after cyproterone acetate and combined oral hormonal contraceptive suggested improved neuronal processing with hormonal treatment. Third, Soleman et al. used a cognitive task to extend the findings of activation pattern differences between PCOS women at baseline and control women. In PCOS women, hormonal treatment decreased the number of errors made while performing cognitive task, suggesting improved executive functioning. Although it is difficult to tell if cognitive processing improved because of cyproterone acetate treatment of hyperandrogenism alone or because of the addition of combined oral contraceptive (control women did not take combined oral contraceptive pills), hormonal treatment did affect both regional activation with N-back task and cognitive task performance. It is notable that PCOSwomen had increased activation of regions of brain associated with cognitive processing while performing the working memory task. Although women with PCOS had similar performance on this complex working memory task compared with control women, increased acti-