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Medscape
4 days ago
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- Medscape
Hyperinsulinemia Linked to Abnormal Uterine Bleeding
Hyperinsulinemia appears to have an early association with common causes of abnormal uterine bleeding (AUB), particularly in women with obesity, a preliminary study in Menopause found. Although preliminary, the study data suggested the opportunity for future research on potential relationships between cardiovascular disease risk factors and gynecologic disease. 'Many studies and organizational bodies have examined and asserted a relationship between polycystic ovarian syndrome (PCOS) and elevated insulin levels,' wrote investigators led by Andrea C. Salcedo, DO, MPH, of the Department of Obstetrics and Gynecology at Loma Linda University in Loma Linda, California. They noted that AUB is the most common reason for benign gynecologic consultation in the United States. Andrea C. Salcedo, DO, MPH 'After over 15 years of clinical practice , I started realizing there were several patterns in women who presented with irregular or heavy periods. Many were self-referred or sent by their primary care providers to see me to evaluate for female hormone problems,' Salcedo told Medscape Medical News . 'The majority were not in perimenopause, but they had similar risk factors for cardiovascular disease, such as obesity, hypertension, and migraine headaches.' Salcedo began to wonder whether healthcare providers are recognizing abnormal periods in reproductive age as a cardiovascular risk and using them to educate women on prevention rather than solely treating them medically or surgically. 'I believe that the theory of the uterus as an 'end organ' that receives inflammation in the same way as the heart and kidneys do in cardiovascular disease helps explain to the patient the reasons for heavy or irregular periods.' The study findings came as no surprise to her: 'They confirmed the patterns I was seeing clinically.' Hyperinsulinemia is associated with smooth blood vessel inflammation in the peripheral circulation. 'What is often under-recognized is that the uterus is made of these same blood vessels.' When the uterus is on the receiving end of inflammation, the blood vessels are damaged and do not function appropriately. The result can be uterine fibroids or heavy periods. The gynecologic expression of this inflammation can vary from person to person, she added. The Study This exploratory cross-sectional analysis of the association between hyperinsulinemia and biomarkers of metabolic syndrome in reproductive-aged women with AUB was designed to motivate future hypothesis-driven research. It was conducted from June 2019 to August 2023 at a single institution's outpatient gynecology clinics. A total of 205 premenopausal women aged 18-54 years were enrolled, including 116 with AUB and 89 control individuals with normal menstrual cycles. Approximately 40% in each group were identified as Hispanic. Participants underwent assessment for fasting insulin and additional markers of metabolic syndrome, including body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and waist-to-hip ratio. Among the findings: • Hyperinsulinemia, the main effect of interest, was a significant predictor of AUB, affecting 44.0% of the AUB group vs 33.7% of the control group, with an odds ratio of 3.0 (95% CI, 1.372-6.832; P = .0085). • Hypertension, LDL, HDL, smoking, migraines, and polyps or fibroids were all significantly associated with AUB and identified as confounders. Chronic hypertension was identified in 26% of the AUB group vs 12% of the control group. • Interestingly, including BMI in the model diminished the significance of hyperinsulinemia, suggesting overlapping or mediating pathways, the authors said. • Among metabolic markers, LDL levels were similar between groups, while HDL levels were lower in women with AUB (54.0 vs 60.0 mg/dL). • There was a nonsignificant intergroup difference in triglycerides (82.0 vs 73.5 mg/dL) and total cholesterol levels (169.0 vs 172.5 mg/dL). • Migraines were more prevalent in the AUB group (31.0% vs 11.2%), as were polyps or fibroids (45.7% vs 9.6%). Commenting on the study but not involved in it, Maureen Whelihan, MD, a gynecologist at the Center for Sexual Health and Education and Elite GYN Care of the Palm Beaches in Greenacres, Florida, called the study an interesting one, 'suggesting that before we see the effects of PCOS, a diagnosis of hyperinsulinemia can be made and managed and that hyperinsulinemia has a direct effect on microinflammatory injury to the uterus.' Maureen Whelihan, MD In her practice, women with insulin resistance and PCOS have major infertility issues. 'About 85% are obese and have lipid disorders. While this study indicates we can make a diagnosis earlier by evaluating fasting insulin, the question is, 'then what?'' she said. The ultimate remedy is diet and lifestyle modification. 'The minute patients understand they must eliminate starch and sugar to lower insulin levels and move their body a little, we lose them,' she said. 'They want a quick fix and nothing that requires them to make difficult decisions and drastic modifications. This is the hard part! We can teach them the pathophysiology all day, but they have to commit to a permanent change in the way they approach diet and exercise.' While the study findings are exploratory and preliminary, Salcedo said, they suggest that abnormal periods may have predictive value. 'In many cases, elevated fasting insulin levels, above 10 µU/mL, could be an early sign of cardiovascular and diabetes disease risk.' In this study, elevated insulin levels were associated with AUB, particularly among those with obesity. 'Therefore, when a patient sees her healthcare provider for irregular periods, it could be an excellent opportunity to discuss the known association of menstrual problems with [cardiovascular] risk factors.' Larger, longitudinal studies are needed, however, to confirm the causal mechanisms, Salcedo said.
Medscape
23-05-2025
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- Medscape
Lactation Can Trigger Menopause-Like Symptoms
Many breastfeeding mothers experience menopause-like symptoms of the postpartum condition recently designated genitourinary syndrome of lactation (GSL) in a systematic review reported in Obstetrics & Gynecology . The term was proposed in 2024 after interdisciplinary discussions among obstetricians, gynecologists, and urologists and following recognition of the genitourinary syndrome of menopause (GSM). Though common, this lactation-associated syndrome is a blind spot in postpartum care — underrecognized and undertreated, according to the review's lead author, Sara Perelmuter, MPhil, an MD candidate at Weill Cornell Medical College in New York City, and colleagues. They found a strong association between lactation and a spectrum of symptoms encompassing vaginal atrophy and dryness, urinary issues, dyspareunia, and sexual dysfunction. Sara Perelmuter, MPhil Pooled analysis revealed that vaginal atrophy was prevalent in almost two thirds of postpartum lactating individuals, with breastfeeding women being 2.34 times more likely to experience atrophy than their non-breastfeeding counterparts. The impetus for this review came from the increasing recognition of GSM. 'Yet silence still existed around postpartum lactating individuals who are essentially going through the same physiological experience of a lack of estrogens and androgens,' Perelmuter told Medscape Medical News . 'I was constantly frustrated by how many postpartum patients — especially lactating individuals — experienced debilitating vaginal and urinary symptoms, yet no one named it, asked about it, and very few providers treated it.' This is a physiologic, hormonal, and wholly real condition affecting millions, and it was time it had a name and clinical recognition, she added. Despite its high prevalence, consistent screening at postpartum visits and treatment guidelines are not available. The American College of Obstetricians and Gynecologists, for example, has issued no guidance on GSL. The authors urged clinicians to prioritize awareness, screening, and personalized care to address these underrecognized symptoms and improve quality of life of lactating mothers. Mechanisms During postpartum lactation, high levels of prolactin inhibit estrogen and androgen secretion. 'If you're not lactating, your hormones are able to rebalance faster, whereas if you're lactating, the hormonal shifts are more dramatic due to sustained suppression of estrogen and androgen,' Perelmuter said, noting that exclusively lactating individuals reported a higher burden of symptom severity in all domains. The Review US and international investigators examined 65 eligible studies, of which almost 80% were of high quality. Among the specific findings in postpartum lactating individuals: The prevalence of vaginal atrophy was 63.9% (95% CI, 55.3%-71.6%) and that of dryness was 53.6% (95% CI, 33.6%-72.5%). Meta-analyses for dyspareunia at 3, 6, and 12 months revealed pooled prevalence estimates of 60.0% (95% CI, 45.1%-73.3%), 39.7% (95% CI, 28.9%-51.5%), and 28.5% (95% CI, 26.3%-30.9%), respectively. Pooled odds ratios at these timepoints were 2.33 (95% CI, 1.92-2.83), 2.24 (95% CI, 1.62-3.10), and 1.45 (95% CI, 1.36-1.56), respectively. The pooled prevalence of sexual dysfunction was 73.5% (95% CI, 59.1%-84.2%). The mean Female Sexual Function Index score was 21.5 ± 1.83, indicating significant dysfunction. 'Honestly, we were shocked by how widespread and underrecognized these symptoms are,' Perelmuter said. 'GSL is a hormonal mirror of GSM, but it's happening during what we culturally frame as a joyful and healthy time — early motherhood — but which is also defined by a massive lifestyle shift.' The investigators were also struck by the finding that more than 70% never seek or receive care. 'These symptoms are not a niche problem. They're systemic, frequent, and deeply impactful. The data validated what many of us have seen in clinic but felt powerless to name.' If your postpartum patient is lactating and reporting dryness, pain, or sexual dysfunction, offer treatment, she advised. 'A simple question, a brief explanation, and an offer of vaginal estrogen or pelvic floor therapy can be life-changing. It's time we bring this into mainstream training for primary care, Ob/Gyns, midwives, lactation consultants, and even pediatricians. Our patients are already experiencing it — we just need to catch up.' Irwin Goldstein, MD Commenting on GSL but not involved in the review, Irwin Goldstein, MD, director of San Diego Sexual Medicine and a clinical professor of urology at University of California San Diego, also stressed the urgent need to raise awareness in the medical community and the public. While it's 'normal' to have low levels of reproductive hormones in both menopause and GSL, this normal state 'leads to unwanted and bothersome and distressing symptoms, which, if appreciated, can be treated,' he told Medscape Medical News . 'The safest hormonal treatment would be intravaginal dehydroepiandrosterone. Its mechanism is intracrinologic [within cells], and it does not enter the bloodstream.' For Perelmuter, GSL is part of a larger pattern in which women's pain — especially postpartum — is being ignored and normalized. 'We need to reframe postpartum care as a time of active healing, not passive endurance,' she said. 'This study is just the beginning. Let's build a future where every lactating person has their symptoms taken seriously, their options explained clearly, and their bodies respected fully.'
Medscape
14-05-2025
- Health
- Medscape
Hormone Therapy Safe After Early Salpingo-Oophorectomy
Younger women carrying BRCA 1/2 mutations and intact breasts but with no personal history of breast cancer who undergo bilateral salpingo-oophorectomy (BSO) before age 45 years can safely start systemic menopausal hormone therapy (MHT) and continue it at least up to the average age of menopause (about 52 years). Andrew M. Kaunitz, MD, FACOG, MSCP This was the recommendation of a narrative review in Obstetrics & Gynecology led by Andrew M. Kaunitz, MD, FACOG, MSCP, associate chair of the Department of Obstetrics and Gynecology at the College of Medicine — Jacksonville, University of Florida, Jacksonville, Florida. In addition to reducing menopausal symptoms and enhancing quality of life, MHT appears to help prevent coronary events and improve bone health and quality of life. Moreover, estrogen-only MHT appears to substantially reduce breast cancer risk. In patients older than 45 years at surgery, however, MHT has been associated with a threefold higher risk for breast cancer, underscoring the importance of factoring in age during risk assessment. To reduce future risk for ovarian, tubal, and peritoneal cancer, the National Comprehensive Cancer Network guidance recommends BSO for BRCA1 or BRCA2 carriers between age 35 years and 40 years and between age 40 years and 45 years, respectively. Many BRCA mutation carriers, however, are reluctant to undergo lifesaving BSO, recognizing that hot flashes and other menopausal symptoms will likely result and having concerns about the safety of MHT. 'Keep in mind that many of these women have relatives who were diagnosed with and sometimes died from breast cancer,' Kaunitz told Medscape Medical News. ' Given that the general population of women — and clinicians — feel that MHT is dangerous, it's understandable that high-risk women would have even greater concerns regarding its safety.' Although most appropriately counseled mutation carriers proceed with risk-reducing surgery — about 67% according to Kauntiz — 'a substantial minority do not, with one prominent reason being concerns regarding the safety of MHT.' Molly J. Pederson, MD Nevertheless, 'it's critical to raise clinician awareness and confidence in prescribing MHT to this group,' commented Molly J. Pederson, MD, a professor of medicine at the Cleveland Clinic Lerner College of Medicine and the clinic's director of medical breast services in Cleveland, who was not involved in the review. As observational data suggest MHT is safe and long-term prospective studies have not raised concerns, 'depriving a young surgically menopausal woman without contraindications to MHT can be devastating both in terms of quality of life and in preservation of bone and cardiovascular health,' she said. Compared with natural menopause, surgical menopause involves a more rapid decline in serum estrogen levels and more severe vasomotor symptoms, as well as higher rates of sleep disturbances, mood disorders, arthralgias, sexual dysfunction, and impaired quality of life. On the therapeutic front, the comprehensive review covered a range of systemic and topical treatments, both hormonal and nonhormonal, for multiple problems including vasomotor and genitourinary symptoms and sexual dysfunction. Treatments comprised testosterone therapy, antidepressants, fezolinetant, and elinzanetant, which are now under review by the US Food and Drug Administration. Lingering Impact of the Women's Health Initiative (WHI) Some of the MHT safety concerns stem from the WHI clinical trials, which assessed oral conjugated equine estrogens (CEEs) and the synthetic progestational agent medroxyprogesterone acetate (MPA) — primarily for cardiovascular outcomes. 'These were the MHT formulations most in use in the 1990s, when WHI was conceived,' Kaunitz said. 'Statistically, the most important adverse impact of MHT was a more than doubling of the risk of venous thromboembolism. Moving beyond WHI, we now recognize that in contrast with oral estrogens, transdermal estradiol does not elevate risk of venous thromboembolism, including pulmonary embolism.' In the WHI, women with an intact uterus were randomized to CEE/MPA vs placebo. 'Good-quality observational data suggest that in contrast with CEE/MPA, which modestly elevates risk of invasive breast cancer, estrogen plus micronized progesterone appears to have little if any impact on risk,' he said. 'In my practice, most of my patients with an intact uterus who are using MHT are using transdermal estradiol plus micronized progesterone.' According to Pederson, MHT use plummeted following the WHI's erroneous announcement in 2002 that 'hormones increased the risk of developing breast cancer by 26%.' 'The publicity around this statistic regarding relative riskhas had dangerous consequences for both patients and providers, creating a bias against MHT that clearly persists.' Reflecting this bias, she added, only about 5% of US women now use MHT, a decline from about 27% in 1999, despite widespread menopause-related quality of life issues. Fortunately, said Kaunitz, attitudes are changing. 'My sense is that my colleagues are receptive to learning about newer data pointing the way toward safer approaches to MHT.' But there remains a significant unmet need for educating clinicians to provide appropriate care for individuals at highest risk for breast cancer, including underserved minority populations underrepresented in clinical trials and observational studies.
