Rethinking the causes of pilonidal sinus disease: a matched cohort study.

Our understanding of pilonidal sinus disease (PSD) is based on a paper published 29 years ago by Karydakis. Since then, surgeons have been taught that hair more easily penetrates wet skin, leading to the assumption that sweating promotes PSD. This postulate, however, has never been proven. Thus we used pilocarpine iontophoresis to assess sweating in the glabella sacralis. 100 patients treated for PSD and 100 controls were matched for sex, age and body mass index (BMI). Pilocarpine iontophoresis was performed for 5 min, followed by 15 min of sweat collection. PSD patients sweated less than their matched pairs (18.4 ± 1.6 µl vs. 24.2 ± 2.1 µl, p = 0.03). Men sweated more than women (22.2 ± 1.2 µl vs. 15.0 ± 1.0 µl in non-PSD patients (p < 0.0001) and 20.0 ± 1.9 µl vs. 11.9 ± 2.0 µl in PSD patients (p = 0.051)). And regular exercisers sweated more than non-exercisers (29.1 ± 2.9 µl vs. 18.5 ± 1.6 µl, p = 0.0006 for men and 20.7 ± 2.3 µl vs. 11.4 ± 1.4 µl, p = 0.0005 for women). PSD patients sweat less than matched controls. Thus sweating may have a protective effect in PSD rather than being a risk factor.

Ageing augments ß-adrenergic cutaneous vasodilatation differently in men and women, with no effect on ß-adrenergic sweating.

NEW FINDINGS: What is the central question of this study? ß-Adrenergic receptor activation modulates cutaneous vasodilatation and sweating in young adults. In this study, we assessed whether age-related differences in ß-adrenergic regulation of these responses exist and whether they differ between men and women. What is the main finding and its importance? We showed that ageing augmented ß-adrenergic cutaneous vasodilatation, although the pattern of response differed between men and women. Ageing had no effect on ß-adrenergic sweating in men or women. Our findings advance our understanding of age-related changes in the regulation of cutaneous vasodilatation and sweating and provide new directions for research on the significance of enhanced ß-adrenergic cutaneous vasodilatation in older adults. ABSTRACT: ß-Adrenergic receptor agonists, such as isoprenaline, can induce cutaneous vasodilatation and sweating in young adults. Given that cutaneous vasodilatation and sweating responses to whole-body heating and to pharmacological agonists, such as acetylcholine, ATP and nicotine, can differ in older adults, we assessed whether ageing also modulates ß-adrenergic cutaneous vasodilatation and sweating and whether responses differ between men and women. In the context of the latter, prior reports showed that the effects of ageing on cutaneous vasodilatation (evoked with ATP and nicotine) and sweating (stimulated by acetylcholine) were sex dependent. Thus, in the present study, we assessed the role of ß-adrenergic receptor activation on forearm cutaneous vasodilatation and sweating in 11 young men (24 ± 4 years of age), 11 young women (23 ± 5 years of age), 11 older men (61 ± 8 years of age) and 11 older women (60 ± 8 years of age). Initially, a high dose (100 µm) of isoprenaline was administered via intradermal microdialysis for 5 min to induce maximal ß-adrenergic sweating. Approximately 60 min after the washout period, three incremental doses of isoprenaline were administered (1, 10 and 100 µm, each for 25 min) to assess dose-dependent cutaneous vasodilatation. Isoprenaline-mediated cutaneous vasodilatation was greater in both older men and older women relative to their young counterparts. Augmented cutaneous vasodilatory responses were observed at 1 and 10 µm in women and at 100 µm in men. Isoprenaline-mediated sweating was unaffected by ageing, regardless of sex. We show that ageing augments ß-adrenergic cutaneous vasodilatation differently in men and women, without influencing ß-adrenergic sweating.

Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.

NEW FINDINGS: What is the central question of this study? Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress? What is the main finding and its importance? A 7-day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post-supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat-stressed older individuals. ABSTRACT: This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole-body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7-day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 µmol l-1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole-body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment-by-time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.

Caffeine and heat have additive but not interactive effects on physiologic strain: A factorial experiment.

This study tested the interactive effects of heat and caffeine on exercise-induced physiological strain by using a 2x2 within-subjects factorial design. Thirty-five physically fit Caucasians underwent a bout of exercise under four conditions wherein ambient conditions (heat vs no heat) and caffeine (placebo vs caffeine; double-blinded) were manipulated. Exercise consisted of a 60-min walk and 5-min step/squat test while wearing weighted backpack. Primary outcomes include measures of physiologic strain (Core temperature [Tr] and heart rate [HR]). Secondary measures included blood pressure, markers of sweat loss, and creatine kinase (CK). Repeated measures models were created to evaluate the individual and combined effects of heat and caffeine. Key results indicated that heat and caffeine significantly increased Tr and HR after walking and stair-stepping. No significant heat by caffeine interactions were detected, and caffeine's main effects were relatively low (≤0.17 °C for Tr and ≤6.6 bpm for HR). Of note, heat and caffeine exhibited opposite effects on blood pressure: caffeine increased both systolic and diastolic blood pressure (by 6-7 mmHg) and heat decreased them (by 4-6 mm Hg; ps < 0.05). In summary, heat and caffeine affected physiologic strain during exercise but exhibited no synergistic effects. In contrast, neither factor affected muscle damage. Clinical implications for heat illness risk in the military are discussed.

Pressure-and dose-controlled, needle-free, transcutaneous pneumatic injection of botulinum neurotoxin-A for the treatment of primary axillary and palmoplantar hyperhidrosis.

BACKGROUND: Botulinum neurotoxin (BoNT) effectively downregulates the secretion of eccrine sweat glands in patients with axillary and palmoplantar primary hyperhidrosis (PH). OBJECTIVE: To demonstrate the efficacy and safety of pressure- and dose-controlled, needle-free, transcutaneous pneumatic injection (TPI) of BoNT-A for treating axillary and palmoplantar PH. METHODS: Needleless TPI-BoNT-A treatments were delivered on the axillary or palmoplantar skin at a pneumatic pressure of 2.05 bars and an injection volume of 0.08 mL/shot. The efficacy thereof was assessed by evaluating starch-iodine test results and Hyperhidrosis Disease Severity Scale (HDSS) scores. RESULTS: At baseline, median HDSS scores were 3 (IQR, 3-4) for axillary lesions and 4 (IQR, 3.5-4) for palmoplantar lesions. Median HDSS scores at 1 month after TPI-BoNT-A treatment significantly decreased to 1 (IQR, 1-1.75) for axillary lesions (P < .001) and 1 (IQR, 1-2) for palmoplantar lesions (P < .001). Median global improvement scale scores were 4 (IQR, 3.25-4) for axillary PH and 3 (IQR, 2.5-4) for palmoplantar PH (P > .05). In all patients, pain was tolerable during treatments for both axillary and palmoplantar PH after the application of topical anesthetic cream. CONCLUSION: Pressure- and dose-controlled, needle-free, BoNT delivery effectively and safely decreased sweating in axillary and palmoplantar skin.

Nicotinic receptors modulate skin perfusion during normothermia, and have a limited role in skin vasodilatation and sweating during hyperthermia.

NEW FINDINGS: What is the central question of this study? What is the role of nicotinic receptors in the regulation of normothermic cutaneous blood flow and cutaneous vasodilatation and sweating during whole-body heating induced following resting in a non-heat-stress condition? What is the main finding and its importance? Nicotinic receptors modulated cutaneous vascular tone during rest in a non-heat-stress condition and in the early stage of heating, but they had a limited role in mediating cutaneous vasodilatation when core temperature increased >0.4°C. Further, the contribution of nicotinic receptors to sweating was negligible during whole-body heating. Our findings provide new insights into the role of nicotinic receptors in end-organ function of skin vasculature and sweat glands in humans. ABSTRACT: Nicotinic receptors are present in human skin including cutaneous vessels and eccrine sweat glands as well as peripheral nerves. We tested the hypothesis that nicotinic receptors do not contribute to the control of cutaneous vascular tone in the normothermic state, but are involved in mediating cutaneous vasodilatation and sweating during a whole-body passive heat stress in humans. We first performed a nicotinic receptor blocker verification protocol in six young adults (one female) wherein increases in cutaneous vascular conductance and sweating elicited by 10 mm nicotine were blocked by administration of 500 µm hexamethonium to confirm effective blockade. Thereafter, 12 young males participated in a passive heating protocol. After an instrumentation period in a non-heat-stress condition, participants rested for a 10 min baseline period. Thereafter, oesophageal temperature was increased by 1.0°C using water-perfusion suits. Cutaneous vascular conductance, sweat rate, active sweat gland density and sweat output per individual gland were assessed with and without 500 µm hexamethonium administered via intradermal microdialysis. Hexamethonium reduced cutaneous vascular conductance by 22-34% during normothermia and the early stage of heating. However, this effect was diminished as oesophageal temperature increased >0.4°C. Active sweat gland density was reduced by hexamethonium when oesophageal temperature was elevated by 0.4-0.6°C above baseline resting. However, this was paralleled by a marginal increase in sweat gland output. Consequently, sweat rate remained unchanged. We showed that nicotinic receptors modulate cutaneous perfusion during normothermia and the early stage of heating, but not when core temperature increases >0.4°C. Additionally, they play a limited role in mediating sweating during heating.

A combined, bioidentical, oral, 17ß-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause.

Introduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17ß-estradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS. Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus. Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.

Efficacy and Safety of Botulinum Toxin A in Axillary Bromhidrosis and Associated Histological Changes in Sweat Glands: A Prospective Randomized Double-Blind Side-by-Side Comparison Clinical Study.

BACKGROUND: The efficacy of botulinum toxin A (BTX-A) therapy in axillary hyperhidrosis has been documented; however, there are a few studies reporting the efficacy of BTX-A in treating axillary bromhidrosis. The histological changes occurring in sweat glands after BTX-A treatment are also unknown. OBJECTIVE: The authors report on the efficacy and safety of BTX-A in the treatment of axillary bromhidrosis and on the histological changes in sweat glands after BTX-A treatment. MATERIALS AND METHODS: Nineteen patients were included in this study. The patients were administered BTX-A injection in one axilla and sterile normal saline as placebo in the other axilla. The degree of malodor was evaluated subjectively by the patients before and 3 months after treatment. Sweat secretion was quantified by the gravimetric method. All patients underwent standard apocrinectomy in both axillary regions. RESULTS: The mean degree of malodor and mean sweat production in the BTX-A-treated axilla were significantly lower than those in the control axilla (2.42 vs 8.00; p < .0001 and 13.33 vs 33.75 mg/min; p = .0028, respectively) at 3 months after therapy. The histological studies showed apocrine sweat glands with atrophic changes and hypoplasia in treated axilla. CONCLUSION: BTX-A injection is an easy, fast, noninvasive method of treating axillary bromhidrosis.

Characteristics of adverse events of endocrine therapies among older patients with breast cancer.

PURPOSE: To clarify the profile of adverse events from endocrine therapies in older patients. METHODS: We surveyed 15 subjective symptoms including hot flashes, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, lethargy, forgetfulness, depressive state, irritated state, genital bleeding, leukorrhea increase, vaginal dryness, bone fracture, and weight gain by a questionnaire among 2044 patients over 55 years old (total number of answered sheets, 8875) and compared the results according to age (56-69 years old vs. ≥ 70 years old) and type of therapy (aromatase inhibitors (AIs) vs. selective estrogen receptor modulators (SERMs)). Among patients 56-69 years old, 6093 and 314 responses were from patients treated with AIs (1477 patients) and SERMs (123 patients), respectively, and 2292 and 176 responses were from those ≥ 70 years old treated with AIs (581 patients) and SERMs (51 patients), respectively. RESULTS: In patients ≥ 70 years old, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, and lethargy were significantly more frequent/severe with AIs than with SERMs. In those aged 56-69, knuckle stiffness and vaginal dryness were significantly more frequent with AIs than with SERMs, but the opposite occurred for hot flashes, leukorrhea increase, genital bleeding, and weight gain. CONCLUSIONS: Among patients ≥ 70 years old, many symptoms were significantly more frequent/severe with AIs than with SERMs, compared with those aged 56-69, which suggests a difference in the profile of adverse events according to the type of endocrine therapy and the patient's age. It is important to consider the benefits and risks of each treatment to optimize endocrine therapy for older patients.

Dronabinol for the Treatment of Paraneoplastic Night Sweats in Cancer Patients: A Report of Five Cases.

Background: Night sweats significantly impact the quality of life for cancer patients and are often resistant to treatment. Cannabinoids have been shown to modulate cytokine activity and produce hypothermia in animal models, suggesting that they may be a promising candidate for palliation of night sweats in patients with oncologic disease. Objective: Assess efficacy of the oral cannabinoid, dronabinol, for palliation of night sweats in cancer patients. Design: A retrospective record search identified five cancer patients who had tried oral dronabinol for palliation of their night sweats between 2013 and 2016 and subjectively reported on its efficacy. Setting/Subjects: A convenience sample of five patients from the outpatient consultative palliative medicine program at Stanford Medical Center was chosen from a search of past records. Patients were included if they had a cancer diagnosis and complained of night sweats that subjectively interfered with their quality of life. All agreed to try oral dronabinol for palliation of their night sweats. Measurements: Patients self-reported the effect of oral synthetic dronabinol on their night sweats. Results: Treatment of five patients with advanced cancer with synthetic orally administered dronabinol resulted in the successful management of persistent symptomatic paraneoplastic night sweats. Conclusion: Dronabinol and/or medicinal cannabis are promising therapies for palliation of night sweats in cancer patients.

Local arginase inhibition does not modulate cutaneous vasodilation or sweating in young and older men during exercise.

Age-related impairments in cutaneous vascular conductance (CVC) and sweat rate (SR) during exercise may result from increased arginase activity, which can attenuate endogenous nitric oxide (NO) production. We therefore evaluated whether arginase inhibition modulates these heat-loss responses in young (n = 9, 23 ± 3 yr) and older (n = 9, 66 ± 6 yr) men during two 30-min bouts of moderate-intensity cycling (Ex1 and Ex2) in the heat (35°C). CVC and SR were measured at forearm skin sites perfused with 1) lactated Ringer's (control), 2) NG-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibited), or 3) Nω-hydroxy-nor-arginine and S-(2-boronoethyl)-l-cysteine (Nor-NOHA + BEC; arginase-inhibited). In both groups, CVC was reduced at L-NAME relative to control and Nor-NOHA + BEC (both P < 0.01). Likewise, SR was attenuated with L-NAME compared with control and Nor-NOHA + BEC during each exercise bout in the young men (all P ≤ 0.05); however, no influence of treatment on SR in the older men was observed (P = 0.14). Based on these findings, we then evaluated responses in 7 older men (64 ± 7 yr) during passively induced elevations in esophageal temperature (∆Tes) equal to those in Ex1 (0.6°C) and Ex2 (0.8°C). L-NAME reduced CVC by 18 ± 20% CVCmax at a ∆Tes of 0.8°C (P = 0.03) compared with control, whereas Nor-NOHA + BEC augmented CVC by 20 ± 18% CVCmax, on average, throughout heating (both P ≤ 0.03). SR was not influenced by either treatment (P = 0.80) Thus, arginase inhibition does not modulate CVC or SR during exercise in the heat but, consistent with previous findings, does augment CVC in older men during passive heating. NEW & NOTEWORTHY In the current study, we demonstrate that local arginase inhibition does not influence forearm cutaneous vasodilatory and sweating responses in young or older men during exercise-heat stress. Consistent with previous findings, however, we observed augmented cutaneous blood flow with arginase inhibition during whole-body passive heat stress. Thus, arginase differentially affects cutaneous vasodilation depending on the mode of heat stress but does not influence sweating during exercise or passive heating.

Six-Month Comparative Analysis Monitoring the Progression of the Largest Diameter of the Sweating Inhibition Halo of Different Botulinum Toxins Type-A.

BACKGROUND: Excessive sweating is a clinical condition that can be improved with type-A botulinum toxin (BTX-A). OBJECTIVES: To evaluate and compare the largest diameter of sweating inhibition halo (SIH) of 5 different commercially available BTX-A, in five different doses, in a 6-month-long clinical evaluation. METHODS: Twenty-five adult female volunteers were injected in the dorsal trunk area with both 100 units (100UI) and 500 units (500UI) BTX-A products, reconstituted in a ratio of 1:2.5 IU, respectively. Products were applied in five different concentrations (1:2.5U, 2:5U, 3:7.5U, 4:10U, and 5:12.5U). After 30, 60, 90, 120, 150, and 180 days, a starch-iodine test was performed to obtain the largest diameter of each SIH. RESULTS: The higher the number of units used, the larger the SIH p < 0.05 for all BTX-A. However, Botox®, Botulift®, Dysport®, and Prosigne® have pretty likewise SIH along the study, with some few differences for some doses and months between one and another. However, Xeomin® is the BTX-A with the smallest SIH, in comparison with all others, in any dose and period. CONCLUSIONS: Differences were observed among all brands of BTX-As, based on dose and time after injection. Xeomin® provides the smallest SIH in comparison with others BTX-A.

Sweat rate analysis of ivacaftor potentiation of CFTR in non-CF adults.

To determine if ivacaftor (Kalydeco) influences non-CF human CFTR function in vivo, we measured CFTR-dependent (C-sweat) and CFTR-independent (M-sweat) rates from multiple identified sweat glands in 8 non-CF adults. The two types of sweating were stimulated sequentially with intradermal injections of appropriate reagents; each gland served as its own control via alternating off-on drug tests on both arms, given at weekly intervals with 3 off and 3 on tests per subject. We compared drug effects on C-sweating stimulated by either high or low concentrations of ß-adrenergic cocktail, and on methacholine-stimulated M-sweating. For each subject we measured ~700 sweat volumes from ~75 glands per arm (maximum 12 readings per gland), and sweat volumes were log-transformed for statistical analysis. T-tests derived from linear mixed models (LMMs) were more conservative than the familiar paired sample t-tests, and show that ivacaftor significantly increased C-sweating stimulated by both levels of agonist, with a larger effect in the low cocktail condition; ivacaftor did not increase M-sweat. Concurrent sweat chloride tests detected no effect of ivacaftor. We conclude that ivacaftor in vivo increases the open channel probability (PO) of WT CFTR, provided it is not already maximally stimulated.

Hyperhidrosis: Management Options.

Hyperhidrosis is excessive sweating that affects patients' quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae, palms, soles, or craniofacial region not caused by other underlying conditions. Secondary hyperhidrosis may be focal or generalized, and is caused by an underlying medical condition or medication use. The Hyperhidrosis Disease Severity Scale is a validated survey used to grade the tolerability of sweating and its impact on quality of life. The score can be used to guide treatment. Topical aluminum chloride solution is the initial treatment in most cases of primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for axillary, palmar, plantar, or craniofacial hyperhidrosis. Iontophoresis should be considered for treating hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts in severe cases of hyperhidrosis when other treatments fail. Local microwave therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and endoscopic thoracic sympathectomy should be considered in severe cases of hyperhidrosis that have not responded to topical or medical therapies.

Progesterone for treatment of symptomatic menopausal women.

This review's purpose is to highlight evidence that oral micronized progesterone (progesterone) is effective for hot flushes and night sweats (vasomotor symptoms, VMS), improves sleep and is likely safe in menopausal women (who are more than 1 year since last menstruation). Methods include randomized controlled clinical trials (RCT) supplemented with basic science, population and observational data as needed. The barrier to use of progesterone is lack of awareness that safety concerns with estrogen-including 'menopausal hormone therapy' (MHT) are not applicable to progesterone. In a single 3-month RCT, progesterone (300 mg at bedtime) was effective treatment of VMS in 133 healthy menopausal women. It caused an overall 55% VMS decrease, no withdrawal-related VMS rebound and a greater VMS decrease in 46 women with ≥50 moderate-intense VMS/week. Progesterone is equally or more effective than estradiol in improving cardiovascular endothelial function and caused no cardiovascular safety concerns in a 3-month RCT. An 8-year prospective cohort study (E3N) in more than 80 000 menopausal women showed progesterone prevented breast cancer in estrogen-treated women. Multiple RCTs confirm that progesterone (300 mg daily at bedtime) does not cause depression and improves deep sleep. In conclusion, progesterone effectively treats VMS, improves sleep and may be the only therapy that symptomatic women, who are menopausal at a normal age and without osteoporosis, need.

Acute Menopausal Symptoms in Young Cancer Survivors Immediately following Chemotherapy.

PURPOSE: The aim of this study was to evaluate the prevalence of menopausal symptoms in young cancer survivors immediately following the completion of chemotherapy. METHODS: This prospective cohort study followed 124 young females with a new diagnosis of cancer requiring chemotherapy to assess symptoms of menopause before treatment and immediately following chemotherapy. Symptoms were compared before and after treatment using the McNemar test and between cancer patients and 133 similar-aged healthy controls using Pearson χ2 and Fisher's exact tests. RESULTS: Participants undergoing cancer therapy reported more menopausal symptoms compared to controls prior to the initiation of any treatment (hot flashes or night sweats 33 vs. 7%, p < 0.01, trouble sleeping 57 vs. 31%, p < 0.01, headaches 50 vs. 35%, p = 0.02, and decreased libido 36 vs. 16%, p < 0.01) and also reported a greater prevalence of symptoms immediately after cancer therapy compared to pretreatment prevalence (vasomotor symptoms, p < 0.01, vaginal dryness, p < 0.01, decreased concentration, p < 0.01, and body aches, p = 0.01). Cancer patients with lower anti-Müllerian hormone (AMH) levels after treatment (<0.10 ng/mL) had an increased risk of vasomotor symptoms (OR 2.2, p = 0.04), mood swings (OR 2.4, p = 0.03), feeling sad (OR 2.2, p = 0.04), trouble sleeping (OR 2.7, p = 0.02), and decreased libido (OR 3.0, p = 0.03) when controlled for age and cancer type, and the incidence of these symptoms was not affected by the use of systemic hormones or psychiatric medications. Treatment length, use of alkylating agents, pelvic radiation, and marital status were also not associated with the prevalence of menopausal symptoms. CONCLUSIONS: Premenopausal women with a new cancer diagnosis have more menopausal symptoms than females of similar age before and after cancer treatment, the effects of which are not mitigated by systemic hormone use. Decreased AMH levels were associated with an increased likelihood of reporting physiologic symptoms after therapy. IMPLICATIONS FOR CANCER SURVIVORS: This information is imperative for counseling; ultimately, improved symptom management during and after cancer therapies will improve quality of life in young cancer survivors.

Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS).

OBJECTIVE: This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17ß-estradiol (t-E2; 50 µg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. METHODS: Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. RESULTS: Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change -1.27 [o-CEE] and -1.32 [t-E2]) when compared with PBO (-0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (rs = 0.170, P < 0.001 for hot flashes; rs = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. CONCLUSIONS: Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women.