[Endocrine and psychosomatic disorders in patients with amenorrhea].

The article presents data on the relationship of pathogenetic mechanisms for the development of menstrual disorders of functional and organic origin in connection with mental disturbances from the point of view of the psychosomatic concept. According to the latter, functional disorders of the menstrual cycle are considered as psychosomatic, in which gynecological pathology develops as a result of psychopathological illness. A striking example of such a disorder is functional hypothalamic amenorrhea. At the same time, endocrinopathies, such as polycystic ovary syndrome and premature ovarian insufficiency, can also be considered in the paradigm of psychosomatic illnesses of ovarian function due to the high prevalence of anxiety and depressive disorders in this cohort of patients. This review highlights the importance of interdisciplinary collaboration between a gynecologist and a psychiatrist for the most effective reproductive rehabilitation of patients with amenorrhea. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1985.

Impact of secondary amenorrhea on cardiovascular disease risk in physically active women: a systematic review protocol.

OBJECTIVE: The objective of this review is to assess the association between secondary amenorrhea in physically active women and cardiovascular disease risk. INTRODUCTION: It is well established that a woman's risk of cardiovascular disease greatly increases after menopause. The sharp decline in estrogen is seen as a causal factor. Exercise-induced secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's cardioprotective pathways. Further, estrogen may be essential in a woman's endothelial adaptations to exercise. The impact of secondary amenorrhea on cardiovascular disease risk in premenopausal women is not well established. INCLUSION CRITERIA: This review will consider studies that include physically active women experiencing amenorrhea in any country. Only studies that present evidence of cardiovascular disease, alterations to cardiovascular physiology, or data on cardiovascular risk factors (eg, lipid profile changes) will be considered. The review will consider experimental or observational epidemiological study designs. METHODS: Searches will be conducted in CINAHL (EBSCOhost), the Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Two independent reviewers will screen titles, abstracts, and full texts, appraise methodological quality, and extract data from studies. Where possible, studies will be pooled in a statistical meta-analysis in addition to subgroup analyses. Where pooling is not possible, the findings will be presented in narrative format. Certainty of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. REVIEW REGISTRATION: PROSPERO CRD42023360781.

Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer.

Importance: Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. Objective: To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). Design, Setting, and Participants: The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. Exposures: Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis). Main Outcomes and Measures: The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. Results: Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for ≥45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. Conclusions and Relevance: In this cohort study of premenopausal women with breast cancer, persistent CRA was common, although some women recovered menses late, and was associated with worse long-term QOL. This study can help inform risk communication, personalized counseling, and early supportive care referrals for such patients.

A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants.

BACKGROUND: Better tools for post-chemotherapy amenorrhea risk assessment are needed for fertility preservation decision-making. Our aim was to determine the predictors of amenorrhea risk at 12 and 18 months post-chemotherapy in women with breast cancer. METHODS: 142 women with breast cancer were longitudinally followed for their menstrual changes at 6, 12, and 18 months after the completion of adjuvant chemotherapy with an Anthracycline-Cyclophosphamide-based (AC-based) or Cyclophosphamide-Methotrexate +5-Fluorouracil regimen. Pre- and/or post-chemo AMH levels, age, BMI, tamoxifen use, regimen type, and germline BRCA pathogenic variant (gBRCApv) status were evaluated for the prediction of amenorrhea at 6-18 months. RESULTS: In multivariable-adjusted logistic regression, age (p = 0.03) and AMH (p = 0.03) at 12 months, and gBRCApv status (p = 0.03) at 18 months were significant predictors of amenorrhea (areas under the ROC curve of 0.77 and 0.76, for 12 and 18 months, respectively) among 102 evaluable subjects. An undetectable AMH immediately post-chemotherapy was predictive of amenorrhea with <18 month follow-up. In longitudinal analysis estimating time trends, baseline AMH and gBRCApv status was associated with the risk of amenorrhea over 6-18 months; the AMH >2.0 ng/mL group showed attenuated time-trend risk of amenorrhea versus AMH ≤2.0 group (ratio of ORs = 0.91, 95% CI = 0.86-0.97, p = 0.002), while the gBRCApv + showed a steeper time trend, versus the controls (ratio of ORs = 1.12, 95% CI = 1.04-1.20, p = 0.003). CONCLUSIONS: In addition to the pre- and post-treatment AMH levels, gBRCApv status is a novel potential predictor of amenorrhea at 12 and 18 months after chemotherapy. The higher likelihood of amenorrhea in women gBRCApv suggests that they are more prone to losing their fertility post-chemotherapy.

Use of pulsatile gonadotropin-releasing hormone (GnRH) in patients with functional hypothalamic amenorrhea (FHA) results in monofollicular ovulation and high cumulative live birth rates: a 25-year cohort.

PURPOSE: To analyze outcomes of pulsatile administration of gonadotropin-releasing hormone (GnRH) in infertile women diagnosed with functional hypothalamic amenorrhea (FHA). METHODS: A single-center retrospective cohort study was conducted from 1996 to 2020. Sixty-six patients with the diagnosis FHA that underwent therapy using the pulsatile GnRH pump for conception were included and analyzed. The primary outcome was the live birth rate (LBR). Secondary outcomes were the number of dominant follicles, ovulation rate, biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate, and multiple pregnancy rate. A matched control group was selected to compare the birth weight of newborn children. RESULTS: During the study period, 66 patients with FHA underwent 82 treatments (14 of 66 patients had more than one treatment) and a total of 212 cycles (ovulation induction attempts) using pulsatile GnRH. The LBR per treatment was 65.9%. The ovulation rate per cycle was 96%, and monofollicular ovulation was observed in 75% of cycles. The BPR per treatment was 80.5%, and the cumulative CPR per treatment was 74.4%. The miscarriage rate was 11.5%. One dizygotic twin pregnancy was observed (1.6%). Average newborn birth weight (NBW) from patients with FHA was comparable to the control group. CONCLUSION(S): In patients with FHA, excellent pregnancy rates were achieved using the subcutaneous GnRH pump. The high cumulative LBR with normal NBW as well as low rates of multiple gestation indicate that the pulsatile GnRH pump represents a safer and more physiologic alternative to ovulation induction with injectable gonadotropins. TRIAL REGISTRATION: Ethics Committee Northwest and Central Switzerland (Ethikkommission Nordwest- und Zentralschweiz - EKNZ) - Project-ID 2020-01612.

Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial).

PURPOSE: Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). METHODS: Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. RESULTS: Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). CONCLUSION: Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

Chemotherapy-induced amenorrhea and its effects on fertility in long-term female survivors of classic osteosarcoma.

PURPOSE: To explore the effect of chemotherapy-induced amenorrhea (CIA) on female osteosarcoma patients' fertility function, we investigated and analyzed their marital status, fertility, and menstrual status in a retrospective cohort study. METHODS: We selected female osteosarcoma patients from database from January 2004 to December 2013. Patients' characteristics such as age, tumor location, marital status, menstrual status, and fertility status were collected. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 22. RESULTS: A total of 122 female patients met these criteria and finally responded by questionnaire and telephone follow-up. The marriage rate of female osteosarcoma survivors was 50.8% (62/122), which was significantly lower than the control group (p = 0.000). The average marriage age of female osteosarcoma survivors was 25.5, which was obviously higher than the control group (p = 0.000). CIA occurred in 46 (36.1%) patients. We then found that the incidence of CIA was higher in older patients. (p = 0.011). All of the married patients wanted to have children, and 67.8% (42/62) of them had given birth after chemotherapy. The fertility of married patients with CIA was significantly reduced compared to that of married patients without CIA. (p = 0.001). CONCLUSIONS: The patients with CIA have higher risk of impaired reproductive function than those who did not. Fertility preservation option before the start of the chemotherapy is important. And it is much value to record menstrual pattern and detect sex steroid levels after 6 months of therapy in order to be able to evaluate the fertility status.

Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.

CONTEXT: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility. OBJECTIVE: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls. DESIGN: We compared patients with HA to control women. SETTING: The study was conducted at secondary referral centers. PATIENTS AND OTHER PARTICIPANTS: Women with HA (n = 106) and control women (ClinSeq study; n = 468). INTERVENTIONS: We performed exome sequencing in all patients and controls. MAIN OUTCOME MEASURE(S): The frequency of RSVs in 53 IHH-associated genes was determined using rare variant burden and association tests. RESULTS: RSVs were overrepresented in women with HA compared with controls (P = .007). Seventy-eight heterozygous RSVs in 33 genes were identified in 58 women with HA (36.8% of alleles) compared to 255 RSVs in 41 genes among 200 control women (27.2%). CONCLUSIONS: Women with HA are enriched for RSVs in genes that cause IHH, suggesting that variation in genes associated with gonadotropin-releasing hormone neuronal ontogeny and function may be a major determinant of individual susceptibility to developing HA in the face of diet, exercise, and/or stress.

Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer.

PURPOSE: While chemotherapy has improved survival among younger women with breast cancer, it can induce temporary or permanent chemotherapy-related amenorrhoea (CRA), impacting survival benefit, quality of life and, importantly for younger patients, fertility. METHODS: This single institution retrospective study of 107 premenopausal women with early stage breast cancer who received neoadjuvant or adjuvant combined chemotherapy treatment investigates the association of clinicopathological factors (including age-related, gynaecological and tumour-related variables) with CRA and resumption of menses using generalised linear models for univariable and multivariate analyses. RESULTS: 76% of women developed CRA, of which only 40% resumed menses after treatment. Age at time of treatment and at menarche were significantly associated with CRA incidence, with higher rates linked to older age (≥ 40 years) and later menarche (at ≥ 13 years), in both univariable (P = 0.043 and P = 0.009, respectively) and multivariate (P = 0.010 and P = 0.012, respectively) analyses. Age at time of treatment, age at menarche and use of tamoxifen were significantly associated with resumption of menses (with greater resumption rates linked to younger age (< 40 years old), later menarche (≥ 13 years old) or no tamoxifen use status), in both univariable (P < 0.0001, P = 0.002 and P = 0.039, respectively) and multivariate (P = 0.001, P = 0.011 and P = 0.008, respectively) analyses. Menses resumption rates were also significantly higher (P = 0.015) in women with later cessation of menses (after 3-6 chemotherapy cycles rather than sooner). CONCLUSIONS: Age at menarche and, specially, at time of treatment are important risk factors for CRA. These variables could aid decision-making for treatment selection and fertility preservation among premenopausal women with early breast cancer.

Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R).

BACKGROUND: This study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. METHODS: This multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. RESULTS: There were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004-1.317; p = 0.077). CONCLUSION: Temporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

Amenorrhea After Chemotherapy In Breast Cancer Patient.

BACKGROUND: This study was conducted to determine the frequency of amenorrhea after chemotherapy among breast cancer patients". METHODS: Total 201 premenopausal females (having menstruation during the past 6 months at the time of diagnosis) of age 15-45 years and had confirmed diagnosis of breast cancer requiring chemotherapy were included in the study using non-probability consecutive sampling technique. Amenorrhea within 6 months after the completion of chemotherapy was labelled as chemotherapy induced amenorrhea. Data was entered and analysed using SPSS-23. RESULTS: The mean age of the patients was reported as 37.06±5.68 years. Majority of the females were married (86.6%) & multigravida (81.1%). Most of the patients (23.9%) received neoadjuvant chemotherapy followed by surgery and radiotherapy. A total of 129 patients received Adriamycin plus cyclophosphamide followed by paclitaxel as chemotherapy regimen. Out of 201 females, 184 (91.5%) experienced amenorrhea after start or completion of chemotherapy. CONCLUSIONS: The frequency of CIA was very high among breast cancer patients in our study, long term follow-up is needed to see input of CIA on future fertility.

NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy.

BACKGROUND: Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer. METHODS: We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer RESULTS: Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients. CONCLUSION: Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings.

Primary amenorrhea in females attending gynaecological outpatient of a tertiary care hospital at Peshawar.

OBJECTIVE: To determine the aetiological factors of amenorrhea. METHODS: The pilot cross-sectional study was conducted in Government Naserullah Khan Babar Memorial Hospital, Peshawar, Pakistan, from January 2015 to December 2017, and comprised amenorrhea cases. Cases were analysed according to their clinical profile, ultrasound findings and biochemical tests. Data was analysed using SPSS 20. RESULTS: There were 100 patients with a mean age of 22.17±5.52 years (range: 14-36 years). Anatomical defects were the most common cause in 60(60%) patients. Imperforate hymen and transverse vaginal septum were found in 7(7%), 7(7%) patients each, while mullerian abnormalities were found in 46(46%) patients. Hypergonadotropic hypogonadism and polycystic ovarian syndrome were found in 17(17%) patients each. CONCLUSIONS: Anatomical defects were found to be the most common cause among amenorrhea patients.

Prolonged Amenorrhea and Low Hip Bone Mineral Density in Women Living With HIV-A Controlled Cross-sectional Study.

BACKGROUND: Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. METHODS: This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as age- and ethnicity-matched Z-scores) in the Children and women: AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. RESULTS: WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. CONCLUSIONS: WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.

Factors That Impact Fertility after Hysteroscopic Adhesiolysis for Intrauterine Adhesions and Amenorrhea: A Retrospective Cohort Study.

STUDY OBJECTIVE: To identify factors that affect reproductive outcomes after hysteroscopic adhesiolysis in patients with severe intrauterine adhesions (IUAs, scored between 9 and 12 according to the American Fertility Society classification) and amenorrhea. DESIGN: A retrospective cohort study. SETTING: A university-affiliated hospital. PATIENTS: One hundred fifty-one patients with severe IUAs and amenorrhea. INTERVENTION: Patients were diagnosed via hysteroscopy and underwent at least 1 hysteroscopic adhesiolysis between May 2012 and January 2016. MEASUREMENTS AND MAIN RESULTS: Of 151 patients, 12 were lost to follow-up, and 139 were included in the study with a follow-up period ranging from 2 to 6 years. Of the 139 evaluable patients, 107 (77%) recovered with a normal uterine cavity (free of IUAs), 28 (20.1%) had improved uterine cavity (fewer IUAs), and 4 (2.9%) showed no improvement. Moreover, 79 patients (56.8%) recovered with normal menstruation, 54 (38.9%) showed increased frequency of menstruation, and 6 (4.3%) had persistent amenorrhea. Seventy-seven (55.4%) became pregnant, of whom 13 had a spontaneous miscarriage, 11 birthed prematurely (at 31-36 gestational weeks), 44 experienced term delivery, and 9 were still pregnant at the end of the study. Age >32 years (p = .002, odds ratio [OR] = 3.442), >2 surgeries (p = .027, OR = 2.969), cervical canal adhesions (p = .047, OR = 2.112), and disease course >6 months (p = .037, OR = 2.335) were risk factors for infertility in patients with severe IUAs and amenorrhea. CONCLUSION: Younger age, earlier treatment within the disease course, fewer cervical canal adhesions, and fewer surgical procedures improve the reproductive outcome in patients with severe IUAs and amenorrhea.

Bone density status in a large population of patients with anorexia nervosa.

Anorexia nervosa (AN) is associated with multiple medical complications. One of the rare permanent complications of AN is the deleterious effect that it has on a patient's bone mineral density (BMD). We report on the Dual-Energy X-ray Absorptiometry (DXA) findings of 336 consecutive patients with AN. Also, we investigated the effects of different factors on these DXA results. These factors included age, body mass index (BMI), percentage of ideal body weight (IBW), duration of illness, duration of amenorrhea, medications such as proton pump inhibitors (PPI) or selective serotonin reuptake inhibitors (SSRI), tobacco use and 25-hydroxy vitamin D levels. This study demonstrated a concerning high prevalence of reduced bone mineral density in patients with AN. Thus, the implication being that those involved in the care of patients with AN need to be cognizant of this serious complication and not be assuaged by the young age of this patient population.

Outpatient analytic assessment of anorexia nervosa — the importance of venous blood gases / Avaliação laboratorial em ambulatório na anorexia nervosa: a importância da gasometria venosa

ABSTRACT Objective: To evaluate serum biochemical parameters' evolution, especially venous blood gas (VBG), in anorexia nervosa (AN), correlating with clinical parameters. Methods: Retrospective study including out-patient AN adolescents, between January 2014 and May 2017. Three evaluations were compared: t1) first consultation; t2) consultation with the lowest body mass index (BMI) z-score and t3) with the highest BMI z-score. Results: A total of 24 adolescents (87.5% females) were included, mean age of presentation of 14.9±1.7 years, onset of symptoms 6.4±3.2 months before the first visit. In t1, BMI z-score of -1.91±1.11 kg/m2 and ideal weight % of 84.3±9.2. Amenorrhea was present in 88%. In t2 the analytical alterations were: altered VBG in 100%, altered ferritin (72% elevated), altered thyroid function (53% with thyroxine decrease), dyslipidemia (31% elevation of high density lipoprotein, 25% hypercholesterolemia), elevation of urea (25%), elevation of alanine aminotransferase (14%), hypoglycemia (14%), anemia (9%). Respiratory acidosis was present in 91% in t1, 100% in t2 and 94% in t3. There was a significant decrease between t2 and t3 in mean pCO2 (57.2 versus 53.6 mmHg; p=0.009) and mean HCO3 (30.0 versus 28.8 mEq/L; p=0.023). Conclusions: Respiratory acidosis and increased ferritin were common in this group. Respiratory acidosis was the most frequent abnormality with significant pCO2 and HCO3 variation in the recovery phase. VBG should be considered in AN evaluation, once it seems to be important in assessing the severity of the disease and its subsequent follow-up.

RESUMO Objetivo: Avaliar a evolução laboratorial, particularmente da gasometria venosa, na anorexia nervosa (AN), correlacionando os achados com parâmetros clínicos. Métodos: Estudo retrospetivo com adolescentes com AN seguidos em ambulatório, entre janeiro de 2014 e maio de 2017. Foram comparadas três avaliações: (t1) primeira consulta; (t2) consulta com escore Z de índice de massa corpórea (IMC) mais baixo; e (t3) consulta com escore Z de IMC mais elevado. Resultados: Incluídos 24 adolescentes, 87,5% do sexo feminino, idade média de apresentação de 14,9±1,7 anos, início dos sintomas 6,4±3,2 meses antes da primeira consulta. Em t1, escore Z de IMC de -1,91±1,11 kg/m2 e % de peso ideal de 84,3±9,2. Tinham amenorreia 88%. Em t2 as alterações laboratoriais encontradas foram: gasometria venosa alterada em 100%, ferritina alterada (72% elevada), função tiroideia alterada (53% com diminuição da tiroxina), dislipidemia (31% com elevação de lipoproteína de alta densidade, 25% com hipercolesterolemia), elevação da ureia (25%), elevação da alanina aminotransferase (14%), hipoglicemia (14%) e anemia (9%). A acidose respiratória esteve presente em 91% em t1, 100% em t2 e 94% em t3. Verificou-se diminuição significativa entre t2 e t3 da pressão parcial de CO2 (pCO2) média (57,2 versus 53,6 mmHg; p=0,009) e HCO3 médio (30,0 versus 28,8 mEq/L; p=0,023). Conclusões: A acidose respiratória e o aumento da ferritina foram comuns nesse grupo. Acidose respiratória foi a alteração mais frequente, com variação significativa de pCO2 e HCO3 na fase de recuperação. A gasometria venosa deve ser considerada na avaliação laboratorial na AN, pois parece ser importante na avaliação da gravidade e monitorização da doença.

High prevalence of abnormal menstruation among women living with HIV in Canada.

OBJECTIVES: To measure the prevalence and correlates of abnormal menstruation among women living with HIV (WLWH) in Canada. METHODS: We used cross-sectional questionnaire data from the community-based Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), which enrolled WLWH aged ≥16 from British Columbia (BC), Ontario, and Quebec. For this analysis, we excluded women >45 years, who had primary amenorrhea, were pregnant, on hormonal contraception, or who reported history of endometrial cancer, last menstrual period >12 months ago, or premature ovarian failure. The primary outcome was abnormal menstruation (Yes vs No) based on responses to five questions about menstrual regularity, frequency, volume, duration, and intermenstrual bleeding in the six months prior to interview. An exploratory multivariable logistic regression analysis examined independent correlates of abnormal menstruation. RESULTS: Of 1422 women enrolled, 521 (37%) met eligibility criteria. Overall, 55.9% (95% CI:52%-60%) reported abnormal menstruation. In adjusted analyses, abnormal menstruation was associated with having a biologic sister/mother who entered menopause before age 40 (AOR 5.01, 95%CI 1.39-18.03), Hepatitis B co-infection (AOR 6.97, 95%CI 1.52-31.88), current smoking (AOR 1.69, 95%CI 1.55-3.41); and currently taking antiretroviral therapy (ART) (AOR 2.36, 95%CI 1.25-4.45) compared to being ART-naïve. Women in BC had higher adjusted odds of abnormal menstruation (AOR 2.95, 95%CI 1.61-5.39), relative to women in Ontario and Quebec. CONCLUSIONS: Over half of WLWH in this analysis had abnormal menstruation. Correlates of abnormal menstruation include genetic, socio-behavioural factors (province of residence, smoking), Hepatitis B co-infection, and current ART use.

Can improvement in hormonal and energy balance reverse cardiovascular risk factors in athletes with amenorrhea?

Female athletes display a high prevalence of hypothalamic amenorrhea as a result of energy imbalance. In these athletes with amenorrhea, decreased luteinizing hormone/follicule-stimulating hormone secretion leads to deficiency in endogenous estrogen. The severe estrogen deficiency in these athletes may increase cardiovascular risk similar to that in postmenopausal women. This review discusses the potential cardiovascular risk factors in athletes with amenorrhea as a result of hypoestrogenism, which include endothelial dysfunction and unfavorable lipid profiles. We also consider the potential to reverse the cardiovascular risk by restoring energy or hormonal imbalance along the reproductive axis in athletes with amenorrhea.

Management of ovulation induction and intrauterine insemination in infertile patients with hypogonadotropic hypogonadism.

AIM: To investigate the effectiveness of ovulation induction and intrauterine insemination (OI + IUI) in female patients with hypogonadotropic hypogonadism (HH), and to compare the outcomes of different stimulation protocols and cycle characteristics. MATERIAL AND METHODS: The outcomes of OI + IUI treatments in patients with HH diagnosed between 2010 and 2018 were retrospectively evaluated. Cycles using recombinant (rec) luteinizing hormone (LH) or human menopausal gonadotropin (hMG) as LH sources were compared with each other. The cycle characteristics and pregnancy rates of the first cycles were compared with those of the second cycles in patients who underwent 2 or more cycles. RESULTS: Of 104 patients diagnosed with World Health Organization type 1 anovulation, 99 were treated with hMG or rec LH + rec follicle-stimulating hormone (FSH) in a total of 220 cycles. The mean age of the study patients was 27.8 ± 4.6 years (range, 19-39 years). Rec FSH + rec LH was given in 37 cycles, and hMG was used in 183 cycles. The hormone values were as follows: FSH, 1.4 ± 1.6 mIU/mL; LH, 0.7 ± 1.2 mIU/mL; oestradiol, 13 (15.8 ± 12.0) pg/mL; and anti-Müllerian hormone, 2.1 (2.6 ± 1.2) ng/mL. A dominant follicle was observed in 85.7% of the first cycles and in 86.2% of the second cycles. The treatment lasted 17.2 ± 5.0 and 15.5 ± 3.8 days until the human chorionic gonadotropin (hCG) administration day in the first and second cycles, respectively, and the difference was statistically significant (p < 0.05). The cycle cancellation rate was 8.1% (n = 3) in cycles done using rec gonadotropins and 29% (n = 53) in patients stimulated with hMG, and the difference was statistically significant (p < 0.05). The pregnancy rates were 12.7% and 28.3% per cycle and per patient, respectively. The pregnancy rate in hCG-triggered patients (successful stimulation) was 17.1% per cycle in all patients. CONCLUSION: OI with gonadotropins and IUI is a safe, efficient, and relatively cost-effective treatment option in patients with HH, yielding reasonable pregnancy rates per cycle and per patient. The use of rec FSH + rec LH facilitates cycle management but does not positively contribute to pregnancy rates and is more expensive than some other feasible options.