This article reviews the evidence on the diagnosis, epidemiology, etiology, and treatment of insomnia in the context of cancer and proposes several areas for future research. Clinical and diagnostic features of insomnia are described and prevalence estimates of insomnia complaints in cancer patients are summarized. Then, potential etiologic factors (ie, predisposing, precipitating, and perpetuating factors) and consequences of insomnia (ie, psychologic, behavioral, and health impact) in the context of cancer are discussed. Finally, pharmacologic and psychologic treatments previously shown effective to treat insomnia in healthy individuals are discussed as valuable treatment options for cancer patients as well. Because long-term use of hypnotic medications is associated with some risks (eg, dependence), it is argued that psychologic interventions (eg, stimulus control, sleep restriction, cognitive therapy) are the treatment of choice for sleep disturbances in the context of cancer, especially whe...

Insomnia in the Context of Cancer: A Review of a Neglected Problem

This review comprises the pharmacokinetics and pharmacodynamics of natural and synthetic estrogens and progestogens used in contraception and therapy, with special consideration of hormone replacement therapy. The paper describes the mechanisms of action, the relation between structure and hormonal activity, differences in hormonal pattern and potency, peculiarities in the properties of certain steroids, tissue-specific effects, and the metabolism of the available estrogens and progestogens. The influence of the route of administration on pharmacokinetics, hormonal activity and metabolism is presented, and the effects of oral and transdermal treatment with estrogens on tissues, clinical and serum parameters are compared. The effects of oral, transdermal (patch and gel), intranasal, sublingual, buccal, vaginal, subcutaneous and intramuscular administration of estrogens, as well as of oral, vaginal, transdermal, intranasal, buccal, intramuscular and intrauterine application of progestogens are discussed. The various types of progestogens, their receptor interaction, hormonal pattern and the hormonal activity of certain metabolites are described in detail. The structural formulae, serum concentrations, binding affinities to steroid receptors and serum binding globulins, and the relative potencies of the available estrogens and progestins are presented. Differences in the tissue-specific effects of the various compounds and regimens and their potential implications with the risks and benefits of hormone replacement therapy are discussed.

https://www.hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric.pdf

Pharmacology of estrogens and progestogens: influence of different routes of administration.

A review of the literature illustrates the many questions about hot flashes that remain unanswered. My survey addresses some of these questions. The prospective and retrospective descriptions of hot flashes provide a more detailed profile of the hot flash than has previously been available. Further, data from this survey demonstrate that while the patterns of hot flashes may be varied, there are commonalities in hot flash physiology and subjective manifestation. The data indicate that hot flashes may start much earlier and continue far longer than is commonly recognized by physicians or acknowledged in textbooks of gynecology. Studies of hot flash duration must control for age or age at hot flash onset, since the older the subjects, the more potential years of hot flashes and the greater the probability of encompassing the entire period of hot flashes. Hot flashes are not static; patterns may change with time. For some women, hot flashes become less frequent and less intense; for others, hot flashes may continue at hourly intervals well into old age. How common these experiences are for women of all ages still needs to be discovered. As expounded by Kaufert, McKinlay, Goodman, and many others, a greater effort must be made to standardize definitions and question formats as well as to improve methodology in epidemiologic investigations to facilitate comparability between studies and insure that proffered conclusions indeed reflect the questions being asked. Physiological studies are critical counterparts to the epidemiology; yet such studies have been too few. My work, by examining the physiology and psychophysiology of hot flashes, has raised additional questions about central and peripheral inputs that may affect the subjective experience of hot flashes. A more complete understanding of the thermoregulatory, cardiovascular, and psychophysiology of women with hot flashes are compared to women without will facilitate the prediction of who is most likely to be affected and the identification of additional approaches to the management of hot flashes.

Hot Flashes: Epidemiology and Physiologya

ObjectiveTo compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factor

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition.

Background Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. Methods The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patien...

https://www.nejm.org/doi/pdf/10.1056/NEJM199408113310602

Megestrol Acetate for the Prevention of Hot Flashes

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest that menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy. (JAMA1981;245:1741-1744)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=374823&pdfFileName=jama_245_17_025.pdf

Association of Waking Episodes With Menopausal Hot Flushes

Six postmenopausal women with frequent hot flashes underwent an 8-h recording of finger temperature as an objective marker of flushing. Serial measurements of serum LH, FSH, estrone, estradiol, dehydroepiandrosterone (DHEA), androstenedione (Δ), cortisol (F), and progesterone were also performed to identify any acute fluctuations in hormonal concentrations which were associated with the temperature changes. A significant increase (P < 0.001) in the level of LH was found, with a maximal percent change of 34 ± 4% during the 5- to 10- min segment after the onset of the finger temperature rises. This maximal LH increase coincided with a maximal finger temperature increase 7.2 ± 0.7 min after onset. Significant correlations were noted between LH measurements and finger temperature measured simultaneously and 5 and 10 min before the time of the sample, suggesting that the maximal LH increase occurs slightly after the maximal finger temperature elevation. Significant rises of DHEA (P < 0.02), A (P < 0.02), and F...

Gonadotropins, Estrogens, and Adrenal Steroids during the Menopausal Hot Flash*

. A study was conducted of 2 young adult women with pituitary insufficiency and complaints of hot flushes. Both underwent continuous recordings of skin temperature of the finger and skin resistance over the sternum as objective indices of flushing episodes. Frequent blood samples were also obtained during the recordings for the measurement of serum LH and FSH levels. During the 10 h of recording, 12 subjective hot flushes occurred and each was associated with a rise of finger temperature of greater than 1 C. Eighty-five percent of the temperature rises were associated with measurable decreases in skin resistance. The mean interval between flushes, the magnitude of the skin temperature and resistance changes, and the relationship of these changes to the onset of subjective flushes were identical to those observed in symptomatic postmenopausal women. Circulating gonadotropin levels were in the low to low normal range in comparison to values observed in premenopausal women and showed minimal pulsatil...

Yohanan Erlik

Papers

Association of Waking Episodes With Menopausal Hot Flushes

Gonadotropins, Estrogens, and Adrenal Steroids during the Menopausal Hot Flash*

Objectively recorded hot flushes in patients with pituitary insufficiency.

Effect of megestrol acetate on flushing and bone metabolism in post-menopausal women.

Association of Waking Episodes with Menopausal Hot Flushes