Разбор анализов гормонов, советы от специалиста

Спасибо за статью! Я проглядел ее.
Вот это - конструктивный диалог!
Да, признаю, что на основе этой статьи можно сделать вывод, что до 200 мг/д кломифена не угнетают дугу - мое предположение в этой части не подтвердилось. Однако на ее же основе можно сделать вывод, что более 50 мг/д не имеет смысла его принимать:
«No dose relationship was observed in any of these hormonal parameters».
И еще там написано, что дозировки от 100 мг/д могли негативно влиять на организм ухудшением спермограммы, что уже не есть хорошо!
«intermediate dosages (100 and 200 mg/day) caused an increase, decrease, or no change sperm concentration».

Хотелось бы увидеть полный вариант этой статьи - остались некоторые вопросы.

 

Саша, добрый день. Подскажи пожалуйста.

ПКТ по тяжелой схеме

4 недели на 100мг кломида
https://bv.do4a.me/proxy.php?image=https%3A%2F%2Fd.radikal.ru%2Fd08%2F1907%2F17%2F5d64ed4762bf.jpg&hash=7c892fa55179776f1a2c50ef56f5a2aa

затем еще 4 недели на 100мг кломида
https://bv.do4a.me/proxy.php?image=https%3A%2F%2Fc.radikal.ru%2Fc37%2F1908%2F9d%2F4fccee409d15.png&hash=f2df38e77b5337716e451e2ba2485078

Целесообразно ли дальше есть кломид? Или лучше сделать кружок с ХГЧ?
Заранее благодарю

 

Новый флешмоб: На ПКТ предохраняться не нада.

Привет, животные! ))

 

Я не знаю, что ты там надумал себе, но логика выводов мне твоя не понятна! Я всю дорогу говорю про гормоны, препараты и исследования, не упомяная Сашана. Где я ему напакостить хочу?

 

Благодарю.
Пару дней назад ты советовал мне пропить Урсосан для снижения билирубина. У меня он, сколько себя помню, всегда был выше нормы в полтора раза...
А Алат и Асат перед началом все этой эпопеи с лечение бесплодия были следующие:
Алат 52,9 (0-41)
Асат 31,2 (0-38)
Лечений, каким-либо образом связанных с этими показателями, не проводилось.
Получается, на сегодня моя терапия выглядит как-то так: 1 таблетка аностразола каждый день (через день), Полтаблетки клостирбегита каждый день и Урсосан 500-750 мг ежедневно?
Я прошу прощения, если обсуждений моих анализов и ситуации в этой ветке черезчур много...
Большое спасибо.

 

Доктор Скалли, всё таки.

 

Но без Малдера)

 

Скользишь сука!
Про какие твои идеи я знаю? с какой целью ты это написал?

 

Ну пидор он, и хрен с ним, зачем удаляться то? Остынь, горячий носатый парень)

 

Сорри, перепутал)

 

Наверное я ошибся, извини!

Ты смотришь, кто меня лайкает?! )))))
Ну нельзя так Сашан! Не хорошо клеймить и показывать пальцем на людей, которые поддерживают альтернативное мнение. Не хорошо!

Это обнадеживает! )))
Кхммм... Досужий вопрос. А почему тогда раньше банил? )))

 

Банально можно из инструкции к клостилбегиту узнать что рекомендуемая дозировка для мужчин не более 100 мг (обычно 50-100мг) в течении 6 недель, что меньше чем в самой ядреной схеме пкт с учетом накопления кломифена.

 

В интернете написано про индекс де Ритиса. Соотношение Асат к Алат. Так вот написано, что он снижается до 0,6 при гепатитах. А у меня даже меньше того. Подскажи пожалуйста, стоит ли еще и за гепатит волноваться? ...Спасибо...

 

Ну хорошо, коль тему Кломифена мы отчасти рассмотрели, предлагаю разрядить обстановку и решить одну задачку, на которую и у меня нет однозначного ответа. Уточню - никаких революций, разоблачений и срача!
Итак, имеем свежие реальные анализы моего товарища из качалки:






А теперь внимание, вопрос!

Как можно объяснить такие анализы, если человек находится на ГЗТ (Небидо - 1гр/3мес) 7 лет.
Заранее отвечу на вопросы - да, аналогичные анализы (в т.ч. - ЛГ) наблюдаются все эти 7 лет, нет - Небидо не фейковый. Эти анализы сделаны перед очередным приемом Небидо. Человек жалуется на усталость, недостаток энергии днем, плохой сон. Вид его напоминает Горлума из Властелина колец, т.е. дрыщавый и с животиком. Продолжительное время с перерывами "через нехочу" тренируется в качалке со мной, но прогресса нет от слова совсем.
В 14 лет перенес болезнь Ходжкина (лимфогранулематоз) до полной ремиссии.

Уточняющие вопросы приветствуются, что знаю - расскажу.
И да, для плюрализма мнений, прошу Сашана высказаться после остальных желающих.

 

Доброго дня всем!
Идет 5-я неделя курса, Сашан скорректируй пожалуйста дозировки ИА/ИП...



P.S. Для в/у курса, какую схему ПКТ взять? Легкую или среднюю?

 

Доброго дня и тебе лично!
Искренне спасибо за твою версию. С щитовидкой все нормально, анализы прикладываю.

Нет, ты не совсем верно меня понял. Ничего негативного я не имел ввиду. Просто после твоего безусловно авторитетного мнения, других мнений мы, с большой вероятностью, не увидим.

Да, с ненулевым ЛГ я согласен. Я ждал от коллег вопроса об анализах, предшествующих ГЗТ, а они еще интересней настоящих! Что скажешь о них? Выкладываю все недостающие анализы:

 

ХГЧ не назначали совсем. Спермограмма, естественно - зеро!

Там ЛГ и ФСГ кастрата, только вот гонады то работали в то время более чем нормально - 25-27 нмоль/л. Разве такие анализы можно назвать гипогонадизмом, с назначением ГЗТ. При этом самочувствие его было таким же неважным как и сейчас, что собственно и было поводом для обращения к врачу.

Кстати, после первичного приема экзогенного теста он почувствовал заметное улучшение состояния с последующим возвращением к исходному.

Моя версия - это патология, связанная с андрогенной нечувствительностью, когда андрогены в крови есть, а организм их почти не замечает (бывают разные степени резистентности). Об этом я читал в той книжке, которую выкладывал 3 месяца назад перед "уходом". Что скажешь?

Spoiler: Андрогенная нечувствительность

ANDROGEN INSENSITIVITY
Mutations in the androgen receptor are relatively common with over 1000 different mutations recorded by 2012 (224) in the McGill database (http://androgendb.mcgill.ca/) making androgen insensitivity the most frequent form of genetic hormone resistance. As the androgen receptor is an X chromosomal gene, functionally significant AR mutations are effectively expressed in all affected males because they are hemizygous. By contrast, women bearing these mutations (including the obligate heterzygote mothers of affected males) are silent carriers without any overt phenotype because they have a balancing allele as well as their circulating testosterone levels never rise to post-pubertal male levels sufficient to activate AR mediated effects.

Germline AR mutations produce a very wide spectrum of effects from functionally silent polymorphisms to androgen insensitivity syndromes that display phenotypes proportionate to the impairment of AR function and, thereby, the degree of deficit in androgen action (1). These clinical manifestations extend from a complete androgen insensitivity syndrome (CAIS, formerly known as testicular feminization) which produces a well developed female external phenotype in a spectrum spanning across all grades of undervirilized male phenotype to, at the other extreme, a virtually normal male phenotype. The severity of androgen insensitivity can be categorized most simply as complete, partial and mild although a more detailed 7 stage Quigley classification based on degree of hypospadias, phallic development, labioscrotal fusion and public/axillary hair is also described (1, 203). The degree of urogenital sinus derivative development together with testis descent provide clinical clues to the degree of androgen sensitivity. In addition, somatic androgen receptor mutations, notably generated during androgen deprivation treatment of prostate cancer (225), result in generation and expression of mutations and splice variants of the androgen receptor in a form of accelerated molecular evolution which may result in resistance to androgen effects and/or efficacy of androgen deprivation treatment (226).

CAIS due to completely inactivating AR mutations results in a 46XY individual with a hormonally active testis that secretes abundant testosterone but which cannot activate AR-mediated action so no male internal or external genitalia or somatic features develop. However, testosterone aromatization to estradiol is unimpeded, leading to the development of normal female somatic features including breast and external genital development after puberty. The population prevalence of CAIS is estimated to be at least 1:20,000 male births or 1-2% among female infants with inguinal hernia (1). The typical presentation of CAIS is a relatively tall, normally developed girl with delayed puberty and/or primary amenorrhea. The clinical features usually include well developed breasts, hips and female fat pattern deposition, acne-free facial complexion with minimal axillary and pubic hair with testes located within an inguinal hernia or in the abdominal cavity. The uterus and fallopian tubes are absent and the vagina is short and blind ending reflecting unimpeded effects of testicular AMH secretion causing regression of Mullerian structures including the upper third of the vagina. Earlier diagnosis is increasingly possible where a prenatal 46XY karyotype is discrepant from a female phenotype on ultrasound or at birth or among female infants presenting with inguinal hernia (227). The family history may be informative with infertile maternal (but not paternal) aunts consistent with an X-linked inheritance. Laboratory investigations of post-pubertal individuals show elevated blood LH, SHBG (at adult female levels) and testosterone (at adult male levels) prior to gonadectomy. The androgen sensitivity index, the product of LH and testosterone concentrations, is elevated (228). These features reflect high amplitude and frequency LH pulses due to the absence of effective negative androgenic feedback on the hypothalamus as well as the increased LH drive to maintain high-normal male levels of testicular testosterone secretion. In untreated individuals, failure to suppress blood SHBG with short-term, high dose androgen administration may be useful confirmation of androgen resistance (229-230). After gonadectomy, blood LH and FSH increase to castrate levels but are partially suppressed by estradiol replacement therapy.

Long-term management includes (a) reinforcing female gender identity with counseling to cope with eventual infertility and acceptance of the genetic diagnosis, (b) post-pubertal gonadectomy to prevent the risk of gonadoblastoma (especially if the gonad is impalpable) but allowing the completion of puberty balanced against the low risks of tumour at that age and of unwanted virilization due to any residual AR function or mosaicism (231), and (c) post-gonadectomy estrogen replacement therapy to maintain bone density, breast development and quality of life. Long-term bone density is often subnormal for age due not only to the deficit in androgen action but also inadequate post-gonadectomy estrogen replacement, often resulting from suboptimal adherence to medication (116, 232-234). Although the long-term outcomes for AR mutations based on large prospective studies of a consistent management approach remain very limited, the clinical outcomes for individuals with CAIS reared as females are reported as successful (235-236) although some gender role and psychosexual functional outcomes remain suboptimal (237-239).

Partial androgen insensitivity syndrome (PAIS) is characterized by a full range of external genital virilization and breast development from female to male phenotype, reflecting the functional severity of the AR mutation. A simple clinical guide to the severity of the deficit in AR function is provided by the level of testis descent and phallic development. PAIS was originally recognised under a variety of eponymously named syndromes (Reifenstein, Gilbert-Dreyfus, Lubs, Rosewater) and only more recently clearly distinguished from other developmental disorders of 46XY individuals with incomplete virilisation especially those due to steroidogenic enzyme defects. Severe forms of PAIS with minimal AR function produce a predominantly female phenotype with clitoromegaly whereas PAIS with mutations displaying more functional AR are characterized by a male phenotype with various grades of labioscrotal formation (varying from minimal posterior partial labial fusion to labioscrotal fusion and bifid, ruggose scrotum) and hypospadias (urinary orofice ranging from perineal aperture to hypospadia with meatus at locations along penile shaft to the corona), micropenis and gynecomastia, each in inverse proportion to the AR function. These features have been combined into a External Masculinization Score (EMS) ranging from 0 (female) to 12 (male) based on degree of scrotal fusion, phallic development, location of urethral meatus and testis descent each scored 0-3 (240). The biochemical finding in PAIS are similar to those of CAIS but with a wide spectrum of severity from mildly virilized, predominantly female to an undervirilized male phenotype. The increase in blood LH and testosterone are less severe and consistent but the androgen sensitivity index (228) may help confirm the diagnosis of androgen resistance. Unlike CAIS, which usually presents during adolescence with failure of puberty, PAIS usually presents at birth with ambiguous genitalia requiring a crucial and decisive clinical judgement on sex of rearing to be made rapidly. The expert pediatric endocrinologist must balance the need for early genital surgery and vicarious decision-making against the risk of possible subsequent regret by the affected individual as an adult. This makes for inevitably complex, difficult and contentious choices as the available systematic prospective evidence from long-term follow-up of sex or rearing is still limited. Most intersex individuals due to PAIS, especially those with an EMS of 4 or more (241), are raised as males (240). Genital surgery for hypospadias is often required and usually uncertainty remains about the adequacy of the potential for post-pubertal virilization due to either endogenous or exogenous testosterone. If pubertal progression is inadequate, exogenous testosterone may be useful but higher than usual dosage may be required to get satisfactory effects. Long-term follow-up of PAIS raised as males has shown apparently adequate psychosexual function despite phallic underdevelopment, limited somatic virilization and dissatisfaction with outcomes by some patients as adults (239, 242). For those to be reared as females, the management is similar to that for CAIS and involves early genital surgery and pre-pubertal gonadectomy to prevent unwanted virilization.

Mild androgen insensitivity (MAIS) is the most minor form of androgen insensitivity dsplaying near-normal male phenotype with only subtle changes in hair patterns relative to family norms (less body and facial hair, absence of temporal recession or balding) and/or minor defects restricted to spermatogenesis alone. The blood LH and testosterone concentrations are usually but not always elevated although the androgen sensitivity index, the product of serum LH and testosterone concentrations, is more consistently raised. In common with mutations in many other genes, making a clear distinction between the most minor grades of clinical pathology and a silent, functionally insignificant polymorphism is challenging and depends on reproducing experimentally the functional consequences of the mutation in an authentic biological system. Ideally such verification is performed in vivo (eg in genetically modified mouse models) but, as this is laborious and expensive, it is rarely undertaken. The functional verification of putative mutations is usually undertaken by either in silico prediction of functional effects of structural protein changes from sequence data or in vitro studies of cultured cells or cell-free systems aiming to characterize protein functions. Nevertheless, although informative, the biological fidelity of these surrogate endpoints relative to the in vivo effects on androgen action may remain questionable.

All types of mutations have been reported in the AR gene including disruption of the reading frame by deletions, insertions, splice site interruption and frame-shift which usually produce major interference with function as well as the more common single base substitutions with effects ranging from nil to complete functional inactivation. In addition, mutation can produce less common mechanisms of interrupting AR function such as inefficient translation, unstable protein, or aberrant translational start sites all leading to reduced expression of functional AR protein. Mutations occur throughout the AR gene, probably at random; however, those reported are distributed unevenly because the most important functional regions of the gene are sensitive to even minor changes in sequence whereas the more variable regions may tolerate sequence changes without functional consequences. Over 90% of known mutations are single base substitutions which have pathophysiological consequences when they change the amino acid sequence in the functionally critical DBD or LBD regions whereas sequence changes in other regions may not alter AR function thereby constituting silent polymorphisms. For example, despite forming more than half the AR sequence, few functionally important mutations are reported in the NTD (exon1). Those described in exon 1 mostly represent major disruptions of the AR protein due to creation of a premature stop codon, a major deletion or frame shift mutation causing mistranslation onward from exon 1 whereas point mutations are more likely to constitute functionally insignificant (silent) polymorphisms. Mutations in the LBD, comprising ~25% of AR sequence, constitute the majority (~60%) of reported mutations whereas mutations in the DBD, representing ~7% of AR sequence, constitute ~14% of cases (243). The functional effects of these two types of mutations generally differ in that LBD mutations demonstrate various degrees of reduced affinity and/or loosened specificity of ligand binding characteristics whereas DBD mutations demonstrate normal ligand binding but reduced or absent receptor binding to DNA. The profusion of AR mutations has created numerous experiments of Nature with multiple different mutations involving the same amino acid with the physiological consequences depending generally on how conservative is the amino acid substitution. Nevertheless, there are exceptions to such categorization with mutations in regions other than the DBD or LBD sometimes unexpectedly affecting DNA or ligand binding properties presumably through physical interaction effects in the tertiary structure of the AR in its 3 dimensional topography.

The familial occurrence of androgen insensitivity due to X-linked inheritance of mutated AR makes carrier detection and prenatal genetic diagnosis feasible. A carrier female has a 50% chance of having a child bearing the mutant AR allele so they would be either a carrier female or an affected male and 50% of her fertile daughters will also be carriers. A specific mutation detection test needs to be established usually involving PCR-based genotyping for point mutations athough other mutational mechanisms may require more complex genotyping methods. For prenatal genetic diagnosis now usually applied to chorionic villus samples, the genetic diagnosis must be rapid, reliable and efficient. However, accurate genetic counselling relies on the a consistent and predictable phenotype for any specific genotype. This is usually, but not invariably, true for AR mutations as the clinical manifestations for the same mutation are usually consistent in CAIS with rare exceptions (244) whereas for PAIS the phenotype may vary even within a single family with significant implications for sex of rearing and/or need for genital surgery so that skilled genetic counselling is essential (245). Discrepancies in the fidelity of phenotype within families, or between unrelated individual bearing the identical mutation, is relatively common in PAIS and may be attributable to somatic mosaicism (246) or the effect of modifier genes that influence androgen action such as 5a reductase (247). An exotic, complex DNA breakage repair slippage mechanism has also been described to produce mutiple mutations within a single family (248). Wider population genetic screening for AR mutations is not currently cost-effective because, despite diminishing costs for increasingly facile genetic testing, the large number of different mutations featuring diverse mechanisms and variable phenotype which still mostly predict a normal life expectancy but a diminished quality of life that is difficult to cost or cure (249).

Acquired androgen insensitivity during life can arise either through postnatal somatic or germline AR mutations or by non-genetic, non-receptor mechanisms that hinder androgen action. Among overt cases of androgen insensitivity, ~30% are absent in the mother’s germline so must arise as a de novo mutation in the postnatal maternal germline (246) or in the fetal germline soon after fertilization (250). Somatic AR mutations, arising de novo postnatally in the stem cell pool of repopulating cells, are theoretically possible but have not been reported. Somatic AR mutations are relatively common in prostate cancer usually arising in late stage disease palliatively treated by androgen deprivation when AR mutations and functional splice variants are reported (226). The switch of highly androgen dependent prostate cancer cells to an androgen deplete milieu may encourage clonal selection of androgen insensitive sublines to proliferate in the terminal stage of the disease. Genetic instability of prostate cancer cells may also contribute to this process although somatic AR mutations are rare in other cancers such as liver (251) or breast (252) cancer in the absence of androgen deprivation. Somatic AR mutation in prostate cancer cells are responsible for the paradoxical anti-androgen withdrawal syndromes observed with non-steroidal (flutamide, bicalutamide, nilutamide) or steroidal (cyproterone, megestrol) (253-254) treatment. In this state, anti-androgen withdrawal or switch-over (254) produces remission of worsening disease attributable to the occurrence of a de novo AR mutation in prostate cancer cells which alters ligand specificity turning the non-steroidal antiandrogens into AR agonists (226, 255). The LNCaP prostate cell line widely used in cancer cell biology research harbours a mutated AR (T877A) which occurs relatively frequently in prostate cancer metastases and can cause the flutamide withdrawal syndrome (256). Since the Nobel prize-winning discovery in the 1940’s of androgen deprivation as palliative treament of advanced prostate cancer (257), targeting of AR fo treatment of prostate cancer has focused on surgical or medical castration to eliminate AR’s cognate endogenous ligand, testosterone. After transient remission following castration, however, prostate cancers resume growth in the apparently androgen independent terminal, treatment resistant stage of the disease. Although castration eliminates the major (>95%) contribution to overall androgen synthesis, ongoing production of androgens from other tissues expressing steroidogenic enzymes, such as the adrenal (258) and prostate tumors (259), has been proposed to explain the late development of apparent androgen independence. Extensive clinical trials of maximum androgen blockade which aims to more thoroughly ablate androgen action by adding anti-androgens to castration, however, have produced only minimal improvement in survival (260), possibly due to antiandrogens countering the deleterious initial “flare” effect of superactive GnRH analogs used for medical castration. A more effective approach has been the development of abiraterone, a rationally designed, mechanism-based inhibitor of CYP17A1 (17-hydroxylase/17,20 lyase) incorporating a 16-17 double bond to inhibit 17-hydroxylation. Abiraterone has proven effective and well-tolerated in treatment of late stage, apparently androgen independent prostate cancer (261) although the blockade of glucocorticoid and mineralocorticoid synthesis requires adrenal replacement therapy. In addition, newer androgen receptor blockers also provided promising new therapeutic approaches especially for castration-resistent advanced prostate cancer (262).

Acquired androgen insensitivity may occur without AR mutations by mechanisms such as drugs including non-steroidal (flutamide, bicalutamide, nilutamide) and steroidal (cyproterone acetate), drugs that block part of testosterone activation such as 5a reductase inhibitors (finasteride, dutasteride) or estrogen antagonists or aromatase inhibitors. In addition, drugs may have physiological effects or pharmacological actions that oppose various steps in androgen action such as LH and FSH suppression by estrogens or progestins or that cause an increase in circulating SHBG which may influence testosterone transfer from blood into tissues to produce a functional phenocopy of androgen insensitivity.

Acquired androgen insensitivity in various disease states is reported with hormonal findings reflecting impeded androgen action which may be reversible with alleviation of the underlying disease. The disease-related mechanisms that impede androgen action vary but the most frequent is increase in hepatic SHBG secretion due to the underlying disease and/or its drug treatments that impede androgen action by reducing testosterone transport from blood to tissues as part of its overall reduction in metabolic clearance rate of testosterone. For example, in hyperthyroidism, increased blood LH and testosterone concentrations with clinical features of androgen deficiency (263) are mediated by increased circulating SHBG due to thyroid hormone-induced hepatic SHBG secretion (264) whereas in hypothyroidism the reduced blood testosterone and SHBG are rapidly corrected by thyroid hormone repacement therapy (263). In epilepsy, anticonvulsant-induced increase in hepatic SHBG secretion appears to be a common denominator in the near ubiquitous reproductive endocrine abnormalities in men with epilepsy (265). The relative contributions of impaired tissue transfer of testosterone, reduced testosterone metabolic clearance rate (266) or direct anti-androgenic effects of valproate (267) remain to be clarified. A similar mechanism of disease- and/or drug-induced increases in hepatic SHBG secretion may explain apparent acquired androgen insensitivity, often reversible with alleviation of the underlying disease, in various other conditions such as gluten enteropathy (268-269), Wilson’s disease (270), relapsed acute intermittent porphyria (271), acute alcoholism (272), chronic liver disease and transplantation (66, 273).