Optimizing and normalizing the population through hormone therapies in Italian science, c.1926-1950.

This essay explores how hormone treatments were used to optimize and normalize individuals under Italian Fascism. It does so by taking the activities of the Biotypological Orthogenetic Institute - an Italian eugenics and endocrinological centre founded by Nicola Pende in 1926 - as the prime example of a version of eugenics, biotypology, which was based on hormone therapies. This essay first demonstrates that Italian Fascist biopolitics was not only concerned with increasing the size of the Italian population, but also with improving its quality. It suggests that under the Italian Fascist regime hormone therapies became eugenic tools of intervention to improve the Italian race. Second, while Pende's institute purportedly enhanced men and women, its activities show the extent to which the 'techniques of normalization' pursued by the Fascist regime were both systematic and invasive.

The Controversial History of Hormone Replacement Therapy.

The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first results of the Women's Health Initiative (WHI) in 2002, which showed that HRT had more detrimental than beneficial effects, HRT use dropped. The negative results of the study received wide publicity, creating panic among some users and new guidance for doctors on prescribing HRT. The clear message from the media was that HRT had more risks than benefits for all women. In the following years, a reanalysis of the WHI trial was performed, and new studies showed that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Notwithstanding this, the public opinion on HRT has not changed yet, leading to important negative consequences for women's health and quality of life.

Towards optimization of estrogen receptor modulation in medicine.

Women now spend more than one-third of their lives in the postmenopausal years, and the decline of endogenous estrogen production during menopause is accompanied by a series of functional disorders that affect the quality of life. These symptoms could be alleviated or even totally suppressed by menopausal hormone therapy (MHT), initially based on natural estrogens extracted from the urine of pregnant mares (mainly in the USA, using the oral route) and later from the synthesis of the natural estrogen, 17ß-estradiol (mainly in Europe, in particular using the transdermal route). Estrogen receptor (ER) α is the main receptor mediating the physiological effects of estrogens. ERα belongs to the nuclear receptor superfamily and activates gene transcription in a time and tissue-specific manner through two distinct activation functions (AF), AF1 and AF2. In addition to these classical genomic actions, ERα also mediates membrane initiated signaling enabling rapid actions of estrogen, potentially along or in interaction with other receptors. Here, we provide a brief historical overview of MHT, and we then highlight recent advances in the characterization of new treatments based on the association of estrogens with selective estrogen receptor modulators (SERMs) or on the modulation of nuclear or membrane ERα.

The emergence of levothyroxine as a treatment for hypothyroidism.

OBJECTIVE: To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies. METHODS: A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified. RESULTS: Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines. CONCLUSIONS: The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

Correction: History and Future of Treatment of Hypothyroidism.

There is an error in a recent article. The last sentence of the section titled "L-Thyroxine Monotherapy Fails to Restore All Markers of Hypothyroidism" should read "new technology is needed to allow for steady delivery of L-triiodothyronine" (it currently reads "… for steady delivery of L-thyroxine").This has been corrected in the online version.

The History and Future of Treatment of Hypothyroidism.

Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone-treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.

HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM.

OBJECTIVE: To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies. METHODS: A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature. RESULTS: A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products. CONCLUSION: The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.

Historical approach to the surgical treatment of erectile dysfunction.

INTRODUCTION: Throughout human history, erectile dysfunction has represented one of the most omnipresent health problems. This has resulted in a search for solutions that, one after the other, have been shown to be fruitless. In this context, the emergence of possible surgical solutions at the start of the 20th century represented a revolution that, even then, would take several decades to demonstrate their effectiveness. ACQUISITION OF EVIDENCE: We performed a literature review that shows the process in the development of potential surgical treatments for hormonal restoration for erectile dysfunction, followed by the sudden emergence of vascular surgery, with new anastomosis techniques, and in the future, the development of penile prosthetic implants as alternative treatments. SUMMARY OF THE EVIDENCE: The publication of results from erectile dysfunction surgery has been lagging for decades due to a lack of objectivity, given that sexual function is a topic restricted by patients' privacy. This situation has led to a reliance on results reported by various authors whose actual credibility could not be verified, with subsequent demonstrations showing that some of these results were not reproducible. CONCLUSIONS: This article reviews some of the most important milestones in the progress of surgeries designed to treat erectile dysfunction. The achievements and apparent failures provide a reason for reflection on how we far we have come and how far we can go in the near future.

[Doctor Brown-Sequard's therapy]. / La thérapeutique du docteur Brown-Séquard.

Pioneer in the field of hormone therapy, Charles-Edward Brown-Séquard (1817-1894) tried to stop the effects of aging on his contemporaries by injecting animal testicle extracts. His therapy was very popular in the last years of the 19th century. He even had followers in the following century, amongst whom Serge Voronoff (1866-1951), who grafted monkey testicles in replacement of human ones, or Paul Niehans (1882-1971) who practiced therapy using calf embryo cells in Switzerland.

Terapia de reposição de testosterona: a polêmica / Testosterone replacement therapy

A terapia de reposição de testosterona (TRT) é uma opção de tratamento para a andropausa, porém é evitada por ser historicamente associada com o surgimento de câncer de próstata (PCa) clinicamente detectável. Esta crença, suportada por mais de meio século, tem sido muito contestada ultimamente por possuir lacunas científicas importantes. O presente trabalho faz uma revisão da literatura recente e aborda as evidências que sustentam a prática e aplicação clínica de TRT e os novos estudos que procuram esclarecer qual a verdadeira relação de dependência entre crescimento do PCa e hormônios andrógenos.

Guilt by association: a historical perspective on Huggins, testosterone therapy, and prostate cancer.

INTRODUCTION: A long-standing belief is that higher testosterone (T) will increase the risk of prostate cancer (PCa), yet recent studies do not support this view. AIM: To identify the key historical and scientific events leading to the establishment and persistence of the belief in a T-dependent model of PCa growth, despite evidence to the contrary. METHODS: Review of key historical scientific articles regarding T and PCa. RESULTS: The T-dependent model of PCa growth arose from the work of Huggins and coworkers, who in 1941 demonstrated dramatic responses to castration among men with advanced PCa. These authors and others also reported a rapid clinical progression with T administration. This led to the concept that T was like "food for a hungry tumor" for men with PCa. Fowler and Whitmore recognized in 1981 that the negative effect of T administration did not occur unless men had been previously castrated. However, this critical observation was either forgotten or dismissed amid major changes in PCa diagnosis and management during the 1980s. More recent studies have failed to provide clinical evidence supporting the belief that higher T represents a risk for PCa. Factors contributing to the persistence of the T-dependent model included dramatic effects of castration, continued use of androgen deprivation for treatment of PCa, an influential spokesperson (Huggins), groupthink (failure to acknowledge evidence inconsistent with the prevalent ideology), and an imprecise formulation of the model ("more T, more cancer growth"), making refutation difficult. CONCLUSIONS: The fear that higher T will increase PCa growth stems from a theory of T-dependent PCa growth that originated with observations in a special population (castrated men) that is not particularly relevant to T therapy in hypogonadal men. The negative view of T with regard to PCa should be recognized for what it is--guilt by association.