Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?

CONTEXT: It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. EVIDENCE ACQUISITION: This review is based on a collection of primary and review literature gathered from a PubMed search of "hypothyroidism," "levothyroxine," "liothyronine," and "desiccated thyroid extract," among other keywords. PubMed searches were supplemented by Google Scholar and the authors' prior knowledge of the subject. EVIDENCE SYNTHESIS: In most LT4-treated patients, normalization of serum thyrotropin levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, for example, specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels. CONCLUSIONS: After excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients who have persistent symptoms or metabolic abnormalities despite normalization of serum thyrotropin level. New clinical trials focused on symptomatic patients, genetic makeup, and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.

Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

OBJECTIVE: We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. PARTICIPANTS: The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by a systematic review of controlled trials conducted on men with a mean T < 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee. CONCLUSIONS: We recommend T supplementation (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Bioidentical hormone therapy: a review of the evidence.

Bioidentical hormone therapy (BHT) uses bioidentical hormones (BHs), derivatives of plant extracts chemically modified to be structurally indistinguishable from human endogenous hormones. BHTs are available commercially or can be compounded into different dosages and for different routes of administration. Typically, compounded preparations of BHs may include estriol, estrone, estradiol, testosterone, micronized progesterone, and occasionally dehydroepiandrosterone (DHEA). It is generally accepted that estrogen-based hormone therapies share similar efficacies as well as risks. Many FDA-approved and regulated pharmaceutically manufactured and branded conventional hormone therapies (CHTs) employ BHs. Since the publication of the Women's Health Initiative (WHI) trial results publicizing an increased risk of stroke, venous thrombosis, and breast cancer and no beneficial effect on coronary heart disease (CHD), use of CHT has declined, and there has been increased interest in alternative approaches. This review of the literature related to compounded BHT and the practices of its advocates is to determine if sufficient scientific evidence supports claims of greater efficacy and safety and any additional risks and uncertainties not generally associated with CHTs. Compounded BHTs have been promoted by some as natural, safer, and in some cases more efficacious than conventional hormone therapies, but there is a dearth of scientific evidence to support these claims. Compounded BHTs lack well controlled studies examining route of administration, pharmacokinetics, safety, and a critical, science-based rationale for the mixture and ratios of bioidentical estrogens employed in many preparations. Many advocates of compounded BHTs customize prescriptions based on saliva tests or blood sera levels in direct contradiction to evidence-based guidelines, which support tailoring HT individually according to symptoms. Currently, scientific uncertainties associated with compounded BHTs make their use less preferable to that of CHTs, as CHTs have been and continue to be assessed by clinical trials regarding both benefits and risks and are indicated for use according to evidence-based guidelines.

Terapia hormonal da menopausa: posicionamento do Departamento de Endocrinologia Feminina e Andrologia da SBEM em 2004 / Hormonal therapy of menopause: 2004 position of the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology and Metabolism

Após os estudos clínicos randomizados produzirem impacto e questionamentos sobre terapia hormonal da menopausa (THM) na comunidade médica, o Departamento de Endocrinologia Feminina e Andrologia da SBEM reuniu um grupo de especialistas para formular um documento informativo, crítico e de posicionamento que pudesse servir de orientação aos que praticam ou opinam sobre tratamento da menopausa. THM está indicada para alívio dos sintomas motores, conservação do trofismo vaginal, preservação de massa óssea e colágeno, melhora do bem estar e sexualidade. Os estudos sobre prevenção cardiovascular primária não são conclusivos, portanto insuficientes para indicar ou deixar de indicar THM com este objetivo. Esquemas e tipos de associação devem ser individualizados. Sempre que possível deve-se optar pelas menores doses eficazes de 17-beta estradiol, associado a progesterona natural ou seus derivados nas mulheres com útero. A duração do tratamento é vinculada a seus objetivos, devendo ser reavaliada periodicamente através de um balanço individual entre indicação e contra-indicação. Orientação quanto a um estilo de vida mais saudável, com eliminação de tabagismo, alimentação adequada em cálcio e pobre em gorduras e atividade física regular são fundamentais como cuidados associados durante a menopausa.

[Hormonal therapy of menopause: 2004 position of the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology and Metabolism]. / Terapia hormonal da menopausa: posicionamento do Departamento de Endocrinologia Feminina e Andrologia da SBEM em 2004.

After randomized clinical trials produced impact and questions at the medical community on menopause hormonal therapy (MHT), the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology convened a group of specialists to produce an informative, critical and position paper, offering guidelines for those who practice or are called to express their opinion on menopause therapy. MHT is indicated for relief of vasomotor symptoms, maintenance of vaginal tropism, bone mass and collagen preservation, sexual and general well-being. Studies on primary cardiovascular prevention are not conclusive, and thus insufficient to indicate or not MHT for this purpose. Schemes and forms of association should de individualized. Whenever possible, one should use 17-beta estradiol, associated to natural progesterone or its derivatives in women with an intact uterus, at the lowest effective doses. Duration of therapy depends on its aims, and should be periodically re-evaluated through an individual indication/contra-indication balance. Orientation toward a healthier lifestyle, with smoking cessation, adequate calcium intake and a low fat diet, together with regular physical activity is fundamental during menopause.

Pathophysiology and treatment of hot flashes.

Hot flashes affect about three fourths of postmenopausal women and are one of the most common health problems in this demographic group. Dysfunction of central thermoregulatory centers caused by changes in estrogen levels at the time of menopause has long been postulated to be the cause of hot flashes. Treatment should begin with a careful patient history, with specific attention to the frequency and severity of hot flashes and their effect on the individual's function. For mild symptoms that do not interfere with sleep or daily function, behavioral changes in conjunction with vitamin E (800 IU/d) use is a reasonable initial approach. For more severe symptoms, the next step is to determine whether there is a contraindication or a personal reservation to estrogen replacement therapy. For women who are able and willing to use estrogen, it will successfully relieve symptoms by about 80% to 90%. In patients with a history of breast or uterine cancer, treatment with the progestational agent megesterol acetate appears to be a safe alternative that also decreases hot flashes by approximately 80%. For women unwilling or unable to use hormone therapy, one of the newer antidepressant agents can be prescribed. Venlafaxine decreases hot flashes by about 60%. Gabapentin is another drug that appears promising as therapy for women unable or unwilling to use estrogen, and the results of ongoing trials to determine its efficacy are eagerly awaited. The use of clonidine, methyldopa, and belladonna should be discouraged because of their modest efficacy and adverse effects.

A nurse's guide to hormone replacement therapy.

Menopause is a natural event most women experience as they enter their 5th decade. As human life expectancy has lengthened, health issues concerning women in mid-life have become a major focus in holistic, preventive health care, which is heavily influenced by nurses. Controversy continues about the risks and benefits of hormone replacement therapy for women during their years of perimenopause and postmenopause. Evidence is compiling, however, that indicates the benefits of exogenous hormones may outweigh these concerns. As nurses, we must have a current knowledge of hormone replacement therapy to counsel our patients effectively. This article presents information to assist the nurse in meeting this goal.