Table 2 - uploaded by Katherine Laguardia
Content may be subject to copyright.
Context in source publication
Similar publications
دراسة التغيرات النسيجية للرحم البشري في عمر لنساء بعمر الانجاب وسن الساس باستخدام المجهر الالكتروني
Citations
... The inventor (K.D. LaGuardia) had been involved in the first registered clinical trial (Phase 2) on the subject and entitled "The effect of extended-release oxybutynin chloride on vasomotor symptoms in healthy post-menopausal women" (NCT00990886; started in 2004). Results were published in a Conference Paper in 2007 [98] and in a manuscript much later [99]. More recently, a Phase 3 trial (NCT02961790; started in 2016) successfully evaluated the efficacy of lower doses of oxybutynin in the management of hot flashes in women under hormonotherapy or not [100]. ...
Since decades, oxybutynin hydrochloride is prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. Mode of action and metabolism are briefly commented in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea.
For decades, oxybutynin hydrochloride has been prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling the preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. The mode of action and metabolism are briefly addressed in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea.
La carencia estrogénica definitiva de la menopausia provoca síndrome climatérico, atrofia vulvovaginal y trastornos urogenitales, osteoporosis y aumento del riesgo cardiovascular. El tratamiento hormonal sustitutivo de la menopausia es el más eficaz en el tratamiento del síndrome climatérico y en la prevención del riesgo óseo y cardiovascular. Son necesarias alternativas terapéuticas, sobre todo para las mujeres en las cuales el tratamiento hormonal de la menopausia (THM) está contraindicado, pero también para las pacientes que no desean tomar tratamiento hormonal. A pesar de su eficacia en los episodios vasomotores, no se recomienda la administración de tibolona debido al aumento del riesgo de cáncer de mama y de accidentes vasculares. La gabapentina permite una reducción del 45-71% de la frecuencia de las oleadas de calor, con una buena relación eficacia/tolerabilidad a dosis de 900 mg/día. Algunos antidepresivos (inhibidores de la recaptación de la serotonina y de la noradrenalina [IRSN] e inhibidores selectivos de la recaptación de la serotonina [ISRS]) han demostrado en la actualidad su eficacia, con una disminución de la frecuencia de los síntomas del 37-61% en función de las moléculas estudiadas, sobre todo en el caso de la venlafaxina, que con el aumento progresivo de las dosis permite una mejor observancia. La oxibutinina ofrece unos primeros resultados prometedores. Por el contrario, la beta-alanina, los fitoestrógenos, la vitamina E y el cohosh negro no han demostrado eficacia alguna. La acupuntura, la hipnosis y el bloqueo del ganglio estrellado son alternativas interesantes para considerar en el tratamiento de los síntomas vasomotores. La atrofia vulvovaginal se trata con lubricantes, geles hidratantes de acción prolongada o con tratamiento hormonal tópico; todavía está en proceso de evaluación la administración tópica de deshidroepiandrosterona (DHEA) o de testosterona. Por último, el tratamiento de la osteoporosis se basa en los SERM (moduladores selectivos de los receptores de estrógeno), los bifosfonatos y el suplemento vitaminocálcico.
With the advancement of antiretroviral therapy (ART), human immunodeficiency virus (HIV) has become a chronic disease. Women with HIV are now living through menopause. Unfortunately, routine therapies for menopause may have harmful drug interactions with ART. Through the case study of a 52-year-old woman infected with HIV, this article addresses current treatments in menopause in the general population, examines the need for addressing specific considerations in the HIV-positive population, and offers recommendations based on the reviewed literature.
Although many non-hormonal compounds have shown statistically significant benefit over placebo in hot flash randomized controlled trials (RCTs), these studies have varied considerably in basic methodology making it challenging to deduce which compounds have the greatest potential to provide clinically meaningful benefit. This review used evidence-based methodology closely mirroring the FDA and EMEA guidelines as a template to identify "well-designed" RCTs from which effective and clinically meaningful non-hormonal hot flash therapies could be identified. In addition, pertinent safety information was reviewed. Out of 3548 MEDLINE citations and abstracts, 51 well-designed hot flash RCTs were identified. From these trials, gabapentin, oxybutynin ER, desvenlafaxine, soy-derived isoflavones and black cohosh each showed a clinically meaningful treatment effect in at least 1 RCT. Among these 5 compounds, only gabapentin demonstrated consistent and statistically significant benefit over placebo in all of its well-designed RCTs. Desvenlafaxine, soy-derived isoflavones, and black cohosh demonstrated statistically significant benefit over placebo in 75%, 21%, and 17% of the well-designed RCTs for each compound, respectively. There was only 1 well-designed RCT using oxybutynin ER, which showed it to have a robust and clinically meaningful benefit. In terms of safety, there have been cardiovascular risks associated with desvenlafaxine use in postmenopausal women with hot flashes. The use of anticonvulsants, in general, has been associated with an absolute 0.21% increase in suicidal thoughts and behavior. Further research is needed with several of these nonhormonal compounds to replicate these findings and to also directly compare their efficacy and tolerability with those of hormone replacement therapy.
