Abstract
Cosponsoring Associations:
The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the ...Endocrine Society.
Objective:
To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA).
Participants:
The participants include an Endocrine Society–appointed task force of eight experts, a methodologist, and a medical writer.
Evidence:
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
Consensus Process:
One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline.
Conclusions:
FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.
FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof.
Objective To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ...ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Design Randomized controlled trial. Setting Clinical research center at an academic medical university. Patient(s) Seventeen women with FHA were randomized either to CBT or observation. Intervention(s) CBT versus observation. Main Outcome Measure(s) Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T3 ), and total and free thyroxine (T4 ) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Result(s) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T3 , or T4 levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T3 and T4 remained unchanged. Conclusion(s) In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. Clinical Trial Registration Number NCT01674426.
Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy-an indication that the system is functioning ...appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population.
Evaluation and Management of Amenorrhea Pitts, Sarah; DiVasta, Amy D; Gordon, Catherine M
JAMA : the journal of the American Medical Association,
11/2021, Letnik:
326, Številka:
19
Journal Article
Background
Functional hypothalamic amenorrhea (FHA) is a form of chronic anovulation not due to identifiable organic causes and with adverse health consequences. The identification of women with this ...disorder or the precocious identification of women at risk is based on the knowledge of lifestyle risk factors or behaviors such as stress, weight loss, and excessive physical exercise that are known to negatively impact gonadal axis activity.
Methods
In this overview, we described the most common forms of FHA, in particular stress-induced amenorrhea and overtraining-induced amenorrhea. In addition, although its mechanisms can differ from those involved in FHA, we reviewed the available literature on drug-induced amenorrhea, highlighting the clear connection between this condition and psychoactive drugs such as antipsychotics, antidepressants and anti-epilectics thus raising concern about the role that the abuse of substances such as opioids or alcohol can possibly have on the growing unexplained infertility of the female population.
Abstract
Background
In premenopausal patients with human epidermal growth factor receptor 2 (HER2)–positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely ...uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown.
Methods
In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor–positive and –negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided.
Results
A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor–positive disease. Median age was 43 (interquartile range = 38–47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor–positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio aHR = 0.58, 95% confidence interval CI = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor–negative patients.
Conclusions
In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor–positive/HER2-positive early breast cancer patients.
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.
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