Talk:5α-Reductase 2 deficiency

discussion of the article

The book Middlesex, an amazing book, is narrated by Cal who has 5 alpha reductase deficiency and provides a very interesting look at the social ramifications of such a condition. I highly recommend the book, it is very well done. ISBN 0312422156

Edited "testes" to "testicles" for article tone consistency.

Does no one think it appropriate to include the 'Guevodoces'/Dominican Republic information? Varilux 07:31, 3 November 2005 (UTC)

5-alpha reductase deficiency is a syndrome which can be inherited due to inbreeding or genetic founder effects. This is the case for the "guevedoces" (literally testicles at age twelve) in the small town of Salinas, Dominican Republic as well as other isolate communities around the world. It is the impairment of the 5-alpha reductase enzyme which converts the androgen testosterone into its more potent metabolite dihydrotestosterone, or DHT. DHT in utero is responsible for the masculinization of external genitalia and for growth of the prostate gland, as well as some other secondary sexual characteristics, such as acne or beard/facial hair growth. Without 5-alpha reductase, testosterone alone is not potent an androgen enough to fully masculinize the genitalia of an XY individual in utero, resulting in erroneous sexing at birth. At puberty, however, there is a spike in the production of testosterone (as well as other steroid hormones) which bind to the same receptors as that of DHT, which can lead to the sex-altering growth of male muscles, penis, and testes, though usually of subnormal size in the phenotypically female individual.

Would you regulars consider the Quentin bit to be a spoiler?

In my opinion, the book deserves a one sentence allusion in an article like this rather than a synopsis. That serves to alert the reader interested in the topic that the book exists. We have many articles about novels or works of fiction. If you would like to treat the book more fully, make a separate Middlesex article, put in as much detail as you want, and include a spoiler warning like we usually do. My opinion of course. alteripse 23:11, 23 December 2005 (UTC) Oh look, the link turned blue, so we already do have such an article, and that is where I would put details.

Combine with 'Guevedoche'?

There is an existing page under the spelling 'Guevedoche'. I have cross-referrenced that page with this (and added medical and documentary external links to both) but I think they could be combined.

I agree. Only if the name remains "5-alpha-reductase deficiency" :-). Guevedoche is probably the term used to describe the transition during pubertal virilization (I'll look it up, I remember a translation like 'penis at 12'). The Dominican Republic, also Papua New Guiney, have higher incidences of 5-alpha-reductase deficiency-2, probably caused by higher incidence of consanguinity. ---Chbse

I disagree. Guevedoce is more appropriate to talk about the social side of it, and in particularl the effect in PNG and the dominican republic. Cheers! Lauren^♫/∆ 00:27, 2 April 2007 (UTC)

I agree with you, but social implications should be considered as subheadings, or chapter, in the whole 5-ARD2 story, not as seperate wiki. Chbse

Reproduction?

It's generally reported that patients with 5ARD-2 are primarily infertile, due to underdevelopment of seminal vesicles and prostate gland, not to mention the large amount of undescended (non-scrotal) testis found in 2ARD-2 patients (Houk, 2005; Cohen-Kettenis P., 2005). There have been some reports of fathering patients (Grant; 1996, Nordenskjold; 1998, KatzMD; 1997, Ivarsson ;1995), but worldwide there has been little proof of genetic fathering (biological fathers). I'll look up viability of articles (briefly) mentioned above (genitic testing in "fathers" etc.). ---Chbse

Those links would be great to add to the "reproduction" section. Absolutely, they tend to be unable to reproduce without medical intervention. It is tied up in the issue of their gender identity, too; those who identify as "straight women" are unlikely to want to "father" children.

Most IVF techniques are appropriate, assuming the individual hasn't had genital mutilation or gonadectomy due to their intersex status which prevents this.

Cheers! Lauren^♫/∆ 00:22, 2 April 2007 (UTC)

In western culture, if/when these patients are gonadectomized (mainly because of surpression of virilization and risk of developing malignancies) obviously IVF can oppose some problems ;-). However, also in cases of non-gonadectomized patients, it's really the question if these patients can ejaculate viable sperm, mainly due to underdeveloped vas deferens, seminal vesicles and prostate. Sadly, I haven't heared of any investigation on effects of percutaneous testicular sperm aspiration etc... Chbse

Sperm aspiration has a long history of use in people with Cystic fibrosis, who also have a vas deferens defect. The results are quite sucessful with Intracytoplasmic sperm injection (ICSI). Cheers! Lauren^♫/∆ 12:40, 21 April 2007 (UTC)

Sperm aspiration still requires viable sperm cells in vivo. Thoughts are that spermatogenesis is critically impaired in most intersex disorders (DSDs). Chbse

See also

What do you think of adding 17βHSD3 to the "list". Androgen insensitivity has little to do with testosterone biosynthesis... ---Chbse

I assume you mean "17-beta-hydroxysteroid dehydrogenase isoenzyme 3 deficiency"? It can certainly go in the "see also" but is already on the "Intersex" page list. BTW, looking at it, it definately needs a cleanup, don't it?

Cheers! Lauren^♫/∆ 00:26, 2 April 2007 (UTC)

17-beta-hydroxysteroid dehydrogenase isoenzyme 3 deficiency is often abbreviated to the simpler word 17βHSD3. Will certainly work on that page :-). Greetz Chbse

New Chapter Layout?

It's easy to just edit, but maybe we can discuss on the layout of chapters in this wiki. For instance, we can combine Gender, 5-ARD in non-western culture and In popular culture to a major chapter "social interactions" or "social characteristics" or something like that. I think it can improve efficiency for reading the page. Chbse

Biochemistry & steroid synthesis

A collaegue of mine created a picture that shows normal steroid synthesis from cholesterol to dihydrotestosterone (DHT) and gave me permission to use it. I'll work on editing to show the defect on testosterone synthesis in 5αreductase def-2 as well as for 17β-hydrosysteroiddehydrogenesis-3. I've looked up how to upload, but I don't have the time to figure out what type of permission I have etc. Does anybody know if I can just use an outgoing hyperlink and thumbnail, or do I really need to upload to wikipedia? greetingsz Chbse

figured it out. added chapter Biochemistry as well as a supporting image. Greetz Chbse

Nice Nice - I was thinking of a similar one. am working on one for a variety of the intersex pages showing differentiation pathways, but don't hold your breath :) Cheers! Lauren^♫/∆ 12:39, 21 April 2007 (UTC)

Looking forward to seeing them :-). Good luck! Greets Chbse

2 redirects

Redirect from "Guevedoche" should really be "Guevedoce" - the former is either a misspelling or is quite rare.

I'd like to propose as well adding a redirect from "Penis-At-12"/"Penis-At-Twelve" - which is a common translation and often-used title for this phenomenon.

Primary amenorrhea

The articles says that patients "often" suffer from primary amenorrhea. Since they do not have any female internal organs, wouldn't patients ALWAYS suffer from primary amenorrhea? Graymornings 03:13, 7 October 2007 (UTC)

I think the text needs some extending on this. More and more 5ARD patients are currently raised as males (better surgical outcome than 30 years ago, possibly better gender outcome?). Considering amenorrhea, which is a female condition involving ovaries (NOT present in 5ARD), ALL female 5ARD patients suffer from prim. ammenorrhea. Considering the possibility of a present uterus in these patients (rare, often lower portion of the "uterus"), I can imagine estrogen influences (e.g. anticonceptive pills) appearing as mentrual bleeding. Mentrual bleeding is (in my knowledge) not considered as a-menorrhea. These bleedings will always be without an egg cell because there are no ovaries. So summarizing: male 5ARD will most likely be infertile, female 5ARD will most likely have primary amenorrhea. What do you think? Chbse research student of intersexuality and gender identity 08:56, 12 October 2007 (UTC)

Adding to the "often" problem: might suggest that virilisation can be the primary problem. Still needs some refitting though...

research student of intersexuality and gender identity 08:56, 12 October 2007 (UTC)

How does 5αRD affect X-linked genetic disorders?

This is going off on a tangent here, but I'm curious as to whether Dihydrotestosterone (DHT) plays any known role on disorders such as Color Blindness, Hypertrichosis, or Fragile-X syndrome. The article makes it quite clear that men with 5-Alpha Reductase Deficiency (5αRD) do not experience male-pattern baldness, due to lack of DHT (with its scientifically-established role in baldness.)

I'm curious, though, as to whether any research --and not just speculation-- has been pursued with 5αRD's role in other X-linked diseases. I'm also curious about women with 5αRD. While that is definitely not an intersex condition, I can't help but wonder if any verifiable studies have shown a lack of female-pattern baldness among them.

If so, it could potentially add-in a whole new dimension to the article. Pine (talk) 21:53, 15 August 2008 (UTC)

I don't think a lot of research is done concerning 5αRD, other than sex organ effects (eg. intersex;DSD), but I'll look into it and report back. Chbse 10:16, 18 August 2008 (UTC) —Preceding unsigned comment added by Chbse (talk • contribs)

So far found on 5ARD: "The mutation appears to be silent in women. Homozygous 46,XX subjects with 5-alpha-reductase 2 deficiency are phenotypically normal, and have normal menstruation and normal fertility" src: UpToDate —Preceding unsigned comment added by Chbse (talk • contribs) 16:09, 29 August 2008 (UTC)

Cryptorchidism in patients with 5-Alpha-Reductase Deficiency. [?]

I have several questions concerning people with 5-Alpha-Reductase Deficiency. The wikipedia article says that (in childhood) they are often raised as girls because their external genitals are indistinguishable from those of natal females. At puberty, however, they are identified as boys due to —among other sex characteristics— their clitorises growing into (very small) penises and their testes descending.

My first question deals with the location of said testes in a post-pubertal man with 5aRD: How far below his abdomen are said testes located (vis-á-vis a typical, adult man)? I've tried finding images of people with 5aRD —both men and children— but thus far have come up fruitless.

Also, are patients with 5aRD more likely to develop testicular torsion, cancer, and other maladies as a result of this condition? Or is there some other factor that I'm failing to take into consideration?

May these individuals be benefitting from the action of superficial veins (notably, the Great Sapphenous Vein) providing blood to their testes cooler than arterial or deep-vein blood? Has anybody looked into this? Where may one find articles and pictures of this fascinating condition? Pine (talk) 20:48, 14 April 2010 (UTC)

The XY infants are usually not really "indistinguishable from natal female". Natal female is the wrong term. A better one would simply be normal females: whoever wrote natal did not understand the term. However, in regard to the undervirilized XY infants with 5aRD it would be more accurate to say "the genitalia of XY infants with severe 5aRD are so undervirilized as to appear more female than male at birth and many have been assigned and raised as girls." In families that are familiar with the conditions and to doctors familiar with disorders of sexual development, the infants are recognizable as having an abnormality of genital development.

Next question. The testes are often palpable at the top of the scrotal folds or inguinal canals. This is well below the waist.

There is a mildly increased cancer risk in any man whose testes remain undescended. There are not good long term statistics on whether this risk may be greater or less with 5aRD because the condition is so rare. I doubt torsion is more common but have never heard evidence one way or the other about this.

I do not understand exactly what you mean by benefitting from superficial veins providing cooling. Veins carry blood away from organs. Arteries supply it to organs and arterial blood is usually core temperature as it is flowing faster from deep within the body.

Pictures can be found in the medical literature, but the condition is rare enough that I have never seen a "collection" of pictures showing the range of external appearance as can easily be compiled for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Many pediatric endocrinology and a few general endocrinology texts have single pictures of single individuals. Most of the articles in the medical literature with pictures also had pictures of only one or two individuals in each article. These articles can be found by searching pubmed but you generally cannot tell if an article is illustrated from the pubmed info alone. You would need to look up multiple articles in a good medical library. alteripse (talk) 02:29, 15 April 2010 (UTC)

Original Research

===Local names=== The term Guevedoche or Guevedoces is Spanish slang for the condition. It originated in the Dominican Republic, where more than three dozen cases have occurred in the small village of Salinas, all descended from a single individual named Altagracia Carrasco. It stands for the colloquial expression huevo a los doce, which translates literally as "eggs at twelve" ("eggs" being a common slang term for "testicles"). It is also known locally as Machihembras (literally "malefemale"). A similar cluster of cases among the Simbari of the Eastern Highlands of Papua New Guinea has the local name Kwolu-aatmwol ("female thing transforming into male thing").

This was moved to the talk page as it violate WP:OR. Please do not return it to the article without proper citations. -- 174.253.9.190 (talk) 20:39, 17 May 2011 (UTC)

5-AR type I deficiency?

Does 5-AR type I deficiency also cause genitals to not develop normally? Or is only 5-AR type II responsible for penis growtH?

Writing about male and female in intersex conditions

@Maneesh, as a point of common sense (that rare thing...), you can't actually have an intersex condition "in males". You can have an intersex condition "in genetic males" or "in chromosomal males", but the whole point of saying that someone is intersex is that you are saying that person is neither male nor female. We try to keep the language precise on these points, because otherwise we confuse readers. WhatamIdoing (talk) 00:33, 12 July 2021 (UTC)

Intersex isn’t even a medical term anymore. Also I don’t understand the whole logic of intersex mean neither male or female.

This condition used to be called male pseudohermaphroditism.CycoMa (talk) 00:38, 12 July 2021 (UTC)

You are very confused about fundamental MEDRS here and the meaning of the word "intersex". 5-ARD is known as a condition that only affects males (though I've added the report about the condition in females). A little bit of browsing of clinical literature will show you that. Why do you think the 3rd reference in the article is titled "Andrology: Male Reproductive Health and Dysfunction"?Maneesh (talk) 00:41, 12 July 2021 (UTC)

Perhaps it'd be helpful if you supplied the definition of "male" that you were using in that sentence. WhatamIdoing (talk) 01:05, 12 July 2021 (UTC)

Nothing particularly special, just the ones that the references in this article use. Male and female have rather obvious consensus meanings in biology and clinical matters. Maneesh (talk) 01:26, 12 July 2021 (UTC)

I’m just gonna say this, if 50 reliable sources say that 5ARD affects males. Wikipedia says it affects males. It’s that simple. Do we have any sources that says it affects a third sex catergory?CycoMa (talk) 04:45, 12 July 2021 (UTC)

The consensus definition of "male" in biology – as opposed to medicine – is that an individual is male if it produces the smaller size of gametes for its species, and female if it produces the larger gametes. Is that the definition you're using here? WhatamIdoing (talk) 02:23, 12 July 2021 (UTC)

You write this as if I am using some magical definition here. It is the underlying WP:MEDRS that describe 5ARD, the very ones used in this article, that are based in clinical science, state in no uncertain terms that this is a condition that is specific to males. There is no material disagreement between biology and medicine on the term "male" (or "female") for that matter. Maneesh (talk) 02:31, 12 July 2021 (UTC)

Just to demonstrate how uncontroversial this is, a 487-cite article titled "Molecular genetics of steroid 5 alpha-reductase 2 deficiency." says in the first two sentence in the abstract:

Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female.

Rather clear isn't it? I've come to expect that editors without much background knowledge of science will try and suggest that our understanding of sex has changed since the publication of this paper. It hasn't, at all, and it is disingenuous to suggest that it has. Throw a rock on scholar: "High Molecular Diagnosis Rate in Undermasculinized Males with Differences in Sex Development Using a Stepwise Approach". This is not even a little controversial: 5ARD is generally synonymous with the presentation in males, the presentation is females is distinct and reported by WP:RS (the Katz cite I have added). Maneesh (talk) 02:45, 12 July 2021 (UTC)

I write this as if I'm aware that most people believe there is only one "obvious" definition of these basic terms, and are shocked, shocked to discover that other people's "obvious" definition doesn't match theirs.

Do you know which of the multiple "obvious" definitions the sources are using here? It probably isn't the classical biological definition, since that's not a biological source. Among the criteria used for the medical definition of biological male, it's not external anatomical sex, since the people labeled "male" don't usually have a penis. I'd bet that the source wasn't talking about hormonal sex either, since the problem is with a hormone. Is it chromosomal sex or gonadal sex? It could be both.

To prevent people from making incorrect assumptions, then we try to write very precisely. That means avoiding terms like "male" and "female" in connection with DSD/intersex-related conditions.

For example, if the relevant definition of "male" in this source is chromosomal sex, then instead of writing "In males, this condition can result in atypical infant genitalia", it is clearer to write "In people with XY chromosomes..." or "In people with male chromosomal sex..." The reason that it's better and clearer is because that can't be misinterpreted as meaning "In babies with a penis (which your grandchild doesn't have, so obviously the doctor got the diagnosis wrong)". WhatamIdoing (talk) 04:41, 12 July 2021 (UTC)

High quality, highly cited clinical sources on a clinically defined condition state unambiguously that they are generally discussing 5ARD as it occurs in males. I feel silly having to cite wp policy in such a clearcut matter, as the quote above shows, but WP:STICKTOSOURCE if you need it. There is nothing more to say about your confusion around the issue. "Male" (and "female" when it is being described in females) is precisely correct. The reason why clinical sources don't use the inaccurate language like you suggest is that there is no reason why someone with any sex chromosomal aneuploidy could not have 5ARD. All sex chromosomal aneuplodies that you can think of are either male or female. 04:53, 12 July 2021 (UTC)

Accuracy and precision aren't the same thing. The sources can "accurately" call a person male even if it would be "more precise" to call that person "genetically male". I believe that term would be consistent with these sources and also encompass all sex chromosomal aneuploidies. Do you agree? WhatamIdoing (talk) 22:12, 12 July 2021 (UTC)

Definitely not consistent with sources. I've already shown you that. 5ARD as a condition affects males. This is precise, accurate and reflects high quality underlying sources form MEDRS. Nothing more to say. Maneesh (talk) 22:17, 12 July 2021 (UTC)

"Male" is not as precise as "genetic male". A narrower term is always more precise than a broad term. WhatamIdoing (talk) 02:35, 13 July 2021 (UTC)

Not when you use use terms incorrectly as you are. "Genetic male" is not a narrower term than male, some genetic males are not males. Some males and not genetic males. At least WP:RS/MC, WP:RS/AC, WP:UBO apply here. You can find many scientific publications textbooks with 100s of citations that discuss 5-ARD as it applies to males. Please stop bludgeoning at this point. I'd like to ask other editors to step in here and offer their opinion.Maneesh (talk) 03:29, 13 July 2021 (UTC)

If many reliable sources say it affects males, Wikipedia says it affects males.CycoMa (talk) 04:45, 12 July 2021 (UTC)

This is note entirely true; see Wikipedia:Manual of Style/Words to watch for many categories of exceptions, and Wikipedia:Manual of Style/Medicine-related articles#Careful language for a list of ways we adapt what sources say to be clearer.

STICKTOSOURCE itself says "The best practice is to research the most reliable sources on the topic and summarize what they say in your own words, with each statement in the article attributable to a source that makes that statement explicitly. Source material should be carefully summarized or rephrased without changing its meaning or implication." IMO clarifying that by 'male', the sources specifically mean genetic males rather than phenotypic males, or people with male external genitalia, or any of several other definitions of 'male', is well within the advice to "summarize what they say in your own words" and "rephrase without changing its meaning or implication". WhatamIdoing (talk) 22:17, 12 July 2021 (UTC)

I don't think you have a very deep background in biology or medicine. The exact right word for the set of people this condition affects as it usually discussed is the one that serious clinical research uses: males. Maneesh (talk) 22:20, 12 July 2021 (UTC)

Specifically, the kind of males that don't have a penis and do appear to have a vagina, right? WhatamIdoing (talk) 02:36, 13 July 2021 (UTC)

I have no idea what you are saying. Maneesh (talk) 03:29, 13 July 2021 (UTC)

It’s not that they have vaginas, it’s more accurate to say they have underdeveloped penises. That at times develops into a full penis at puberty.CycoMa (talk) 02:38, 13 July 2021 (UTC)

In some cases, the penis is "underdeveloped" to the point that their parents and healthcare professionals say "It's a girl!" when they're born, right? WhatamIdoing (talk) 02:43, 13 July 2021 (UTC)

Have you been around a modern medicine? They don't say that today because it's quite common to test sex chromosomes and see development in ultrasounds. What people say when a baby is born or any sort of misdiagnosis has no bearing on the use of standard vanilla terminology in this article. Maneesh (talk) 03:29, 13 July 2021 (UTC)

This is a grossly inappropriate comment that (1) fails to understand the global nature of Wikipedia, (2) fails to understand that sex chromosome testing of the particular kind necessary to ascertain any trait like 5α-Reductase deficiency is expensive/rare and only likely in high income countries where a sibling or relative has the trait, (3) fails to take into account standard methods of sex determination in this trait that assign sex, in situations of doubt, based on physical characteristics in relation to ease of surgery. I am going to revert the text again. Trankuility (talk) 09:26, 13 July 2021 (UTC)

There doesn't seem to a consensus here. The comment is completely appropriate, misdiagnosis or what people say when babies are born has nothing to do with the content of this article. Most of the world doesn't say "It's a girl" since most of the world doesn't speak English...your context issues seem to be with the original comment. Maneesh (talk) 16:56, 13 July 2021 (UTC)

One can't even write coherently about the epidemiology without referring to males and females. The title of the seminal 1974 paper with 1500+ cites: "Steroid 5 alpha reductase deficiency in man: an inherited form of male pseudohermaphroditism." Maneesh (talk) 17:05, 13 July 2021 (UTC)

You are pushing a POV, Maneesh, and engaging in a fallacy of moving the goalposts - you made inappropriate comments on genetic testing. Now that those comments have been refuted you have moved on to another claim, this one an irrelevant one about the use of English globally. The point about variable access to genetic testing, and a fictive claim about testing for 5αRD though "sex chromosome" testing were wrong. Further, genotypic sex is not the only way of determining sex. Sources - including those cited in this article - vary considerably in their use of terms that you perceive as having a narrow, fixed meaning. Your changes were not warranted and do not meet WP:NPOV. Trankuility (talk) 23:35, 13 July 2021 (UTC)

You make no sense. There is no goal post moving, this is a very straight forward matter, nothing I've said has been refuted. No one is arguing about methods for determining sex. 5ARD is is a condition that is generally discussed it affects the precise category of males. Every single serious clinical source says so, the titles of books say so. It's very simple and straightforward. Maneesh (talk) 00:11, 14 July 2021 (UTC)

You don't know enough about these issues to make any informed judgment, and you impose narrow ideological views on articles with too few active editors. Trankuility (talk) 00:49, 14 July 2021 (UTC)

Trankuility and Maneesh please Wikipedia:Assume good faith assume good faith. Don’t accuse people of POV pushing.CycoMa (talk) 06:10, 15 July 2021 (UTC)

RfC about sex specificity of 5α-Reductase deficiency

The following discussion is an archived record of a request for comment. Please do not modify it. No further edits should be made to this discussion. A summary of the conclusions reached follows.

Consensus was RfC was unclear, closing and opening new one that is more specific. Maneesh (talk) 05:28, 15 July 2021 (UTC)

---

Should the article describe those who are affected by this condition as "males"? Maneesh (talk) 00:20, 14 July 2021 (UTC)

Do you think that the list you have specified is correct for this article? You seem to get away with making radical changes on a range of articles with low numbers of active editors, imposing your narrow views on them. You should stop doing that. Trankuility (talk) 00:47, 14 July 2021 (UTC)

Comment: Please suggest something else from WP:RFC/AT if you think there is a more suitable topic. As for your accusation, I do not need to pollute the RfC with a response. Maneesh (talk) 00:54, 14 July 2021 (UTC)

"pollute"! Trankuility (talk) 01:06, 14 July 2021 (UTC)

• Comment: (Summoned by bot) – I received a bot notification because I've subscribed to Math topics, which doesn't seem to be the case here. Categorization error? Mathglot (talk) 01:47, 14 July 2021 (UTC)

WP:RFC/AT says math, science and technology. There are only a few categories, do you see a better one? Maneesh (talk) 01:51, 14 July 2021 (UTC)

• Maneesh, do you have WP:MEDRS sources to present that can weigh in on this question? Crossroads ^-talk- 05:09, 14 July 2021 (UTC)

They are in the long winding talk page discussion, perhaps the most succinct is to survey highly cited MEDRS source that come from google scholar. "Affected males..." is often seen within the first few sentences of any description. Some example sentences across a number of years: "Steroid 5 alpha reductase deficiency in man: an inherited form of male pseudohermaphroditism.", "Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female.", "Affected males are born with ambiguous external genitalia, despite normal internal genitalia.". The presentation of the condition is (obviously) specific in males, females present the condition distinctly and much less obviously. Maneesh (talk) 05:37, 14 July 2021 (UTC)

Since the title of that last paper is Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency (emphasis added), it seems that the answer to the question ought to be obviously not, unless I am grossly misunderstanding what is being asked. Meanwhile, the first paper, Imperato-McGinley et al. (1974), is the original report on the condition, so it fails the WP:MEDRS standard of not relying on primary sources (use reviews, don't try to write them). As is so often the case with human beings, the best answer might be complicated; per Maimoun et al. (2011), the condition appears compatible with "a wide spectrum of phenotypes and biological profiles". Some studies refer to specific XY individuals diagnosed with 5α-reductase deficiency as "female" outright; e.g., Fénichel et al. (2013) or Maimoun et al. (2011b). Such secondary sources as I am aware of, like Faisal Ahmed et al. (2015), simply refrain from making blanket statements connecting chromosomes with labels applied later in life. XOR'easter (talk) 22:18, 14 July 2021 (UTC)

You are misunderstanding, perfectly illustrating the need for clarity here. You need to be able to understand the condition in males and females. The remarkable effects on genital formation only happen in males. Females can have the same deficiency but there are no (obvious) effects, naturally since the role of DHT in females physiology is not well characterized. The first paper is the original explanation of the known effect at the molecular level, it is not some sort of account of the first report of the phenomenon. There is no conflict with WP:PRIMARY. You are conflating sex and gender, sex specificity isn't complicated here, from your own source (the first sentence actually): "5a-reductase deficiency is a rare, male-limited autosomal recessive disorder caused by mutation in the SRD5A2 gene resulting in a deficiency of dihydrotestosterone (DHT) during fetal development. Sports science source do certainly like to confuse the matter here, they are much lower weight and not WP:MEDRS and tied up with a lot of WP:CONTROVERSIAL issues. Maneesh (talk) 00:33, 15 July 2021 (UTC)

Far from conflating sex and gender, my point is that genetic sex, gonadal sex, and phenotypic sex must be distinguished, and none of them are the same thing as gender; the question asked in the RfC seems to oversimplify the issue in a way that does not do justice to the biology. The RfC refers to "this condition", which I take to mean "the condition of carrying one or more mutations of the 5α-reductase Type II gene". Even if "the condition" is defined more narrowly (e.g., carrying a mutation and having XY karyotype), the literature doesn't lead us to say "male" — more on that in a moment. (And since you write of the need "to understand the condition in males and females", I'm a bit confused about the sense in which the RfC question was posed.) I fail to see how WP:PRIMARY does not come into play for the first explanation "at the molecular level". When a paper introduces an idea, it's a primary source for that idea. Further searches for things that can qualify as reviews (see here) suggest that while the percentage of individuals assigned female at birth who elect to transition to male may be higher than it is with other types of androgen insensitivity syndrome, it is definitely not 100%; moreover, terminology like "male pseudohermaphroditism" has been phased out. So, no, the literature does not support the use of "male" without qualification. XOR'easter (talk) 00:50, 15 July 2021 (UTC)

Many things are complicated about many topics, but the sex-specificity here is not. You totally did conflate them, you claimed things were complicated but your own source said plainly in the first sentence that the condition is male-limited. The set of people primarily affected by this condition as it is generally discussed are males, not females (though we do know a little about them). And no, "carrying a mutation and having XY karyotype" is not the correct set of people since you can find, for instance, cases in XYY with the same condition. WP:PRIMARY: "All analyses and interpretive or synthetic claims about primary sources must be referenced to a secondary or tertiary source..", the molecular biology of 5ARD is well established scientific fact from Imperato-McGinley1974 that you can find many many secondary sources (1500+ cites) on (as I linked in the google scholar search). WP:MERS applies to supporting claims in the article, it does need to be cited in the article as a part of history, I've only put it here to show you how the fact that 5ARD is rather specific to males was established long ago and remains established. I linked and quoted highly cited secondary sources right after Thigpen1992] and Azzouni2011 (which is a review) so I cannot see what your concerns about primary sources are here. I don't think you've understood the importance in characterizing the sex differences in this specific condition. What people identify as is largely not relevant to the fact that the severe form of the condition is clearly male-limited as your own source stated in the first sentence. Easy to find many MEDRS books that say the same thing, like here or use "male development" since it is so obvious. The fact that the term "male pseudohermaphroditism" is being phased out is not relevant to the fact that 5ARD is a severe condition in males. How would you propose describing the differences of the condition in males and females without using the words male and female?Maneesh (talk) 01:36, 15 July 2021 (UTC)

I should also add that OMIM numbers are standard in WP for genetic diseases. From OMIM uses both "male-limited" and "affected males" (and "male" all over). Maneesh (talk) 01:56, 15 July 2021 (UTC)

To answer your question: I'd start by reading the entirety of the articles that say things like "male-limited" in order to grasp the sense in which they mean "male". They distinguish gender from sex (in fact, giving multiple meanings of the latter, all biologically relevant). The question posed in the RfC does not make these distinctions. It does not even specify what "this condition" is. You point to Azzouni (2011), which talks about "affected males" and also mentions the lack of symptoms in "human females". So, it indicates expressly that this article should not describe those who are affected by this condition as "males".

? All the MEDRS source mean male sex. There is no other plausible interpretation. How do you figure it follow if source uses the term "affected males" that the article should not describe those who are affected by this condition as "males"? The article is highlighting that the class of people that the condition does not affect [severely] is the set of females. Maneesh (talk) 02:39, 15 July 2021 (UTC)

No, it is highlighting that the symptoms in XX females affected by the condition are much less severe. XOR'easter (talk) 02:50, 15 July 2021 (UTC)

Where does Azzouni2011 qualify "female" with "XX female"? It wouldn't make any sense because a molecular understanding of 5ARD would lead one to expect the same presentation in XXX females as XX females. You haven't addressed your contradictory statement I highlighted. 03:01, 15 July 2021 (UTC)

Sorry, instead of "XX" I should perhaps have used a locution like "not Y-chromosome-bearing". But as for your other point, I don't see the contradiction. Cf. the pedigree in Fig. 1 of Hochberg et al. (1996), which says that Affected individuals are indicated by filled shapes, including three filled circles for three sisters. Females are described as affected; ergo, we can't say that "those who are affected" are exclusively males. It's really clear-cut. XOR'easter (talk) 03:22, 15 July 2021 (UTC)

Still wouldn't make sense for an XX male. We have words for the categories you are trying to capture: male and female. You are missing the fact that the three females in Hochberg do have the deficiency, but they are not [severely] affected (look at how short the para on female is who seem mostly normal, "Physical examination revealed normal female sexual characteristics, normal pubic hair, and normal breast firmness."). I've already elaborated on how the implicit intent is to refer to the people who are severely affected as males. You do realize that "not Y-chromosome-bearing" is a contrived phrase not used anywhere in MEDRS, don't you?Maneesh (talk) 03:54, 15 July 2021 (UTC)

The "Disorders of Sex Development" book chapter starts by talking about XX males and XY females. In the (short) section on 5α-reductase deficiency, it uses "male" in both the "typical karyotype" sense and to refer to gender identity. This likewise indicates that this article should not describe those who are affected by this condition as "males"; without qualification, the term could be true or false.

5α-Reductase deficiency is simply deficiency in the enzyme activity, it presents in a severe form in males and much less characterized/less symptomatic form in females. The question is implicitly "should the article describe those who are affected by the severe form of this condition as "males"?" Maneesh (talk) 02:39, 15 July 2021 (UTC)

The RfC did not ask that. It might have been clearer and more productive if it did; that's a better question. But if it did, I'd still have to say no, because a reader could be coming to the article with the inclination to read "male" with a sex-meaning or with a gender-meaning, and there is no reason for us to compound their difficulties by confusing the two. XOR'easter (talk) 02:50, 15 July 2021 (UTC)

Sure, if you think that is a deficiency I can close this an open another. So you wouldn't describe sex differences in any disease in terms of male and female? Even though sex is a key biological variable? Wow. Maneesh (talk) 03:01, 15 July 2021 (UTC)

That's not what I said. I simply want to avoid ambiguity and confusion when words have multiple related but distinct meanings. XOR'easter (talk) 03:22, 15 July 2021 (UTC)

So because male and female are words with other meanings, we should not use them to describe sex differences in this disease or any disease?Even though this would counter to essentially all of clinical science? Maneesh (talk) 03:54, 15 July 2021 (UTC)

Is that a strawman, or the slippery slope fallacy?

Nobody has said that the words should not be used when writing about any disease. We're only saying that it would be appropriate to be clear here, in this specific article, about exactly which definition of "male" is the relevant one. WhatamIdoing (talk) 04:54, 15 July 2021 (UTC)

The appearance in the Genetic Consultations in the Newborn book is a brief mention in a list; fine as far as it goes, but not the place for subtlety. If the point is to make careful distinctions, we should lean on the articles that expound at length in prose, not on tabulations. It's easy enough to say, for example, "Individuals with an XY karyotype may present with ambiguous genitalia at birth and later, at puberty, develop characteristics such as..." There's just no need to try shoving all that meaning onto one overburdened word. XOR'easter (talk) 02:25, 15 July 2021 (UTC)

Yikes you think that male is "overburdened word? It is a clear cut sex cateogory. 02:39, 15 July 2021 (UTC)

Your own sources, which use it for both sex and gender, indicate otherwise. So does the lede of the article Male. XOR'easter (talk) 02:53, 15 July 2021 (UTC)

I'm not debating that people can use words in all sorts of ways. MEDRS won't use "male" and "female" in such a confusing way, can you show a quote from my sources that was using male as a sex category and as a gender identity without making it clear what sense was being used? Maneesh (talk) 03:01, 15 July 2021 (UTC)

I don't agree with XOR'easter that using "male" could confuse sex and gender. In a biomedical context, which this is, "male" is always in reference to sex. Even otherwise, it is much more commonly referring to sex, not gender. That is how the relevant sources use it and we have a duty to follow them. I also agree with you above that stating "XX female" could be inaccurate because if the source simply says "female", stating "XX female" excludes other rare karyotypes like XXX female, and thus is misleading and original research. Crossroads ^-talk- 03:12, 15 July 2021 (UTC)

The sources provided by Maneesh use "male" in a biomedical context to refer to gender as well as to sex. For example, It appears that exposure to testosterone in utero, early postnatally, and at puberty have variable contributions to the formation of their male gender identity (pp. 363–4 of Pediatric Symptom-Based Diagnosis). Other usages I turned up: The overall rate of gender change from female to male ranged from 16% to 70%. The lowest rate of gender change from female to male occurred in Turkey and the highest in Brazil. External genitalia virilization was similar between those who changed and those who kept their assigned gender [1]. Or, ... male gender identity does not necessarily represent the rule in these subjects [2]. In short, when medicine includes gender, the terms don't always refer to sex. And this might come down to a judgment call, but both usages seem common enough within the relevant literature that I can't neglect either meaning. A major concern of the medical literature is how to provide the best care, which necessitates bringing identity into the picture. (Edit to add: I clarified the typing-too-fast XX comment above.) XOR'easter (talk) 03:27, 15 July 2021 (UTC)

It's not the sources that are confusing. It's the wording of the RfC. XOR'easter (talk) 03:22, 15 July 2021 (UTC)

I agree that the wording of this RfC is confusing; a common affliction of RfCs. My statement about "male" should have noted that it was speaking of the term as it is used without specification, which is what I understood to the plan for the article generally - all the quotes you give here where it refers to gender use "gender" in that sentence. Otherwise, the sources seem to use "male" without further comment to refer to sex and use "gender" in addition to "male" when they speak of male gender. Crossroads ^-talk- 03:40, 15 July 2021 (UTC)

Yes, heaven knows I've posed plenty of unclear questions here in my day, too. Would it make sense to start over with a more specific question? Maybe with a choice of alternate phrasings for some specific sentences? XOR'easter (talk) 03:49, 15 July 2021 (UTC)

Ok so does "Should this article use "male" as an unqualified term to describe the set of people whose genital appearance is likely to be significantly affected by this condition?" sound ok? Maneesh (talk) 03:55, 15 July 2021 (UTC)

If you think it would be good to open or amend the RfC, happy to do so. I don't think it is such an inferential leap given the context, but happy to do so anyway. The sources are pretty clear with their use of their qualified use of male and female. When MEDRS sources describe 5ARD as "male affected" or "male limited" they mean the the severe presentation only affects those of the male sex. Shouldn't this article do the same? Maneesh (talk) 03:54, 15 July 2021 (UTC)

Maneesh, please be sure to sign with the correct number of tildes. In some comments your username isn't showing up. As far as the RfC goes, I think you should cancel it, and then start a fresh discussion about one or two where you think the current text should be changed and why. Then we can agree or discuss it. No need for a long convoluted RfC on them most likely. Then open another discussion on another spot once that finishes. Splitting it up makes it simpler, and having an RfC encompass all those different contexts is confusing. Crossroads ^-talk- 04:14, 15 July 2021 (UTC)

• If the sentence is about males, use "males". As noted in the discussion above, that appears to be what the sources use in many contexts. Females can also get the condition, but are not as affected; any sentences about them should state "females". If there are any sentences that are ambiguous, they can be clarified in various ways and discussed here. But I see no justification for excluding male and female as terms as that is what the sources use. Crossroads ^-talk- 03:12, 15 July 2021 (UTC)

  I'm not sure that the sources actually do use an unadorned "male" in many contexts at all. Look at the four sources Maneesh quotes here: A paper from 1974, from 1992, one that mentions this condition only in passing while discussing hormone-based treatments for cancer, and from 1996. The selection of such obviously non-MEDRS-quality papers almost makes one suspect that they're the only four that could be found that don't use a phrase similar to "genetic male" at some point.

? You aren't representing the sources I have presented accurately. The 1974 and 1992 are heavily cited seminal papers in our understanding of 5ARD, that is why they were presented since their WP:UBO is very significant. A 2011 review uses "affected males", Azzouni2011, does not use "genetic male". I've already presented other more recent sources but they aren't exactly hard to find: a 40 year retrospective review says "Discovery of 5-alpha reductase deficiency as a syndrome of disordered male sexual development led to our molecular understanding of the role that this key enzyme plays in male sexual differentiation." This is an old condition, most of the most highly cited work on it has already been done. It's getting a little tiresome pulling out the first few sentences on 5ARD articles that clearly describe that the severe presentation only affects males. Maneesh (talk) 05:18, 15 July 2021 (UTC)

• I think this article should use precise language. That means using a phrase such as "genetic male" or "genetic female" when we're describing people according to their chromosomal situation, and using the word "man" or "woman" to describe non-biological gender. For example, we might write that "Runner Caster Semenya is a genetically male intersex woman whose diagnosis with 5α-reductase deficiency resulted in pressure to artificially lower her testosterone levels". WhatamIdoing (talk) 04:40, 15 July 2021 (UTC)

Source analysis

Options	Verifiable?	Clear and correct?	Notes
Male	Yes (5α-Reductase deficiency#cite note-6)	Unclear; correct only for certain definitions	Unclear: There are lots of different ideas about what constitutes "male", and if your idea doesn't match the one that the source's author had in mind, then you'll be confused. Many people think male=penis, and it is incorrect under that definition. In terms of verifiability, the source says "Clinical manifestation of 5-ARD is limited to male genetic. The affected males are usually identified as female in childhood", which does not contradict "genetic male", and it does not entirely inspire confidence in the authors' English skills (what is a "male genetic"?).
Genetically male or genetic males	Yes (e.g., [3][4][5][6], plus 5α-Reductase deficiency#cite note-NieschlagBehre2009-3, 5α-Reductase deficiency#cite note-4, 5α-Reductase deficiency#cite note-6, 5α-Reductase deficiency#cite note-8 among sources already cited in the article)	Clear and correct	Appears to be the winner. I note that the editor who started this RFC relied on 5α-Reductase deficiency#cite note-NieschlagBehre2009-3 as a key source in our earlier discussion. (See " Why do you think the 3rd reference in the article is titled "Andrology: Male Reproductive Health and Dysfunction"?") I encourage him to look at the first paragraph on page 329, where the exact description "genetic males" is used to describe people with this condition – complete with the bold-face type I've copied here from the original.
Karyotypical male	Yes: 5α-Reductase deficiency#cite note-NieschlagBehre2009-3	Clear and correct	The source says "karyotypical male newborns show female external genitalia". "Karyotypical" is more jargon-y than "genetic male".
Female	Yes: 5α-Reductase deficiency#cite note-pmid16098368-2	Confusing; correct only for certain definitions	Describes two siblings as "female" because of their sex assigned at birth ("raised as girls"), and not because of their biological sex. But if your definition is female=no penis, then you'd be right in this case.
Women	Yes: 5α-Reductase deficiency#cite note-10, 5α-Reductase deficiency#cite note-11,	Potentially confusing	This language, and the subject of these papers, is a matter of the Sex and gender distinction. It is probably not DUE.
Male pseudohermaphrodites	Yes: 5α-Reductase deficiency#cite note-sci001-7 and 5α-Reductase deficiency#cite note-9	Clear	These sources are at least 30 years old, and the language is outdated.

Also, 5α-Reductase deficiency#cite note-12 (a newspaper) uses both "biological males" and "female" to report others' views of a group of athletes that included Caster Semenya, who has XY 5α-reductase deficiency.

So having gone through all the cited sources that I could get to open (a motley lot in need of updating) and searched for others, my conclusion is that the sources routinely specify "genetic male". I believe we should follow their lead and do the same. WhatamIdoing (talk) 04:24, 15 July 2021 (UTC)

In this context phrases like "genetic male" or "karyotypic male" are making it clear that despite appearances these people are males and that they do not have any sort of aneuploidy. These are sloppy phrases since XYY males are not karyotypic and can have 5ARD. MEDRS doesn't say things like "5ARD is genetic male limited", that would be silly. No one would ever use "male pseudohermaphrodite" as a sex category. 5ARD has an awfully clear sex difference, would make no sense to describe the males as females, sex differences in human health are always described in terms of male and female, the only two sex categories.Maneesh (talk) 04:38, 15 July 2021 (UTC)

Funny, the "sloppy" source is the one you were encouraging me to trust earlier, when you only wanted me to look at the title of the whole book. But now that it doesn't agree with you, it's the sloppy one? WhatamIdoing (talk) 04:42, 15 July 2021 (UTC)

"Male" isn't sloppy, they didn't accidentally include females in a book that is specifically on males. They are just making it clear that these people are indeed male and that the condition isn't a result of an aneulploidy. Maneesh (talk) 0 04:46, 15 July 2021 (UTC)

Of course they didn't accidentally include females. When they got to the section that is specifically about this condition, and not about enlarged prostates and whatever else andrology covers, they stopped saying "males" and started saying "karyotypic males" and "genetic males". WhatamIdoing (talk) 04:50, 15 July 2021 (UTC)

Your table misrepresents how the overwhelming number of high quality MEDRS sources simply use "male" to refer to sex without qualification. The sex of the people who are likely to be severely impacted by this condition is the male sex. Maneesh (talk) 04:40, 15 July 2021 (UTC)

Great. Give me some links to those high-quality sources? Because most of what's in the table is the sources cited in this article right now. WhatamIdoing (talk) 04:43, 15 July 2021 (UTC)

The links in my posts above are clear, scroll up near the top, look for the AuthorYear style words. Maneesh (talk) 04:46, 15 July 2021 (UTC)

The links you posted above are from decades ago. Here, I'll help you out. Here's a link to Google Books that meet WP:MEDDATE: [7] I see about 120 books there. WhatamIdoing (talk) 04:49, 15 July 2021 (UTC)

Furthemore, CAIS are genetic males who *cannot* be affected by this disease severely. (C)AIS is a commonly misdiagnosis of 5ARD. XY gonadal dysgenesis are also genetic males but not male, they cannot present 5ARD as *males* do. Maneesh (talk) 04:46, 15 July 2021 (UTC)

That article starts off by saying, Because DHT is required for the normal masculinization of the external genitalia in utero, genetic males with 5-alpha-reductase type 2 deficiency are born with ambiguous genitalia (ie. 46,XY disorder of sexual development (DSD)). It certainly seems like "genetic male" is the big-picture, broad-strokes concept they want to go with; further subtleties can be addressed with careful phrasing (e.g., using "may present" or "often present" instead of just the verb "present"). XOR'easter (talk) 05:11, 15 July 2021 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

RfC Sex Differences in 5α-Reductase deficiency

Should the article include a description of sex differences in the presentation of 5ARD? E.g., the body opens with "Individuals with 5-ARD are born with male gonads, including testicles and Wolffian structures." which is not true for females with 5-ARD. Maneesh (talk) 05:37, 15 July 2021 (UTC)

• Comment It seems like the problem with that specific sentence, as well as some others like it, is with the word "Individuals". Sources say "genetic males" [8] or "karyotypic males" [9] (the latter is more jargon-y and apparently less common but definitely still attested). At an intermediate level of popularity between those two options, one can also find the unapologetically blunt "46, XY individuals" [10][11][12][13][14]. The upshot is, we need to be more specific than the article currently is. Well, it also needs more and better sources overall, but that's another issue. XOR'easter (talk) 06:16, 15 July 2021 (UTC)

To be sure, 'male' (and 'female') is a natural way to talk about the two sexes as well. "Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency". "Genetic male" does not occur in that report. If we look at the latest highly cited review I can access, Azzouni2011 there is no occurrence of "genetic male" or "46, XY individuals". Azzouni2011 does use "male" and "female" correctly to describe sex differences. WP:MEDDATE is not an issue here, the condition was characterized long ago and most highly cited reviews were published a while ago. A 2011 review is more than recent enough. Many publications that use terms like "sex of rearing", "gender" etc. are clear when using "male" and "female". When describing who this condition affects in the severe form that tend to use terms like "affected males" in Mendoncaa 2014, and when dealing with important issues like fertility that are clear about sex specificity like in "A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These male infants are born with ambiguous external genitalia..." Kang2014. These sources are representative of the entire body of literature on the subject. Maneesh (talk) 17:55, 15 July 2021 (UTC)

A statement like "representative of the entire body of literature" is a very strong claim. I provided examples above that use more specific terminology; are they not part of the "entire body of literature"? And if there is variation among sources, shouldn't we go with the more specific options that are available and attested? Nor do I quite see how WP:MEDDATE is not an issue; indeed, the sources have explicitly called attention to terminology being changed, e.g., "XY disorders of sex development (XY, DSD; formerly named male pseudohermaphroditism)" [15]. The question posed in this RfC points to the opening line of the article body ("Individuals with 5-ARD are born with..."); per the Mendonca et al. (2014) source that I included above and you also referenced, one appropriate replacement would be "affected 46,XY individuals". Later, the article says of a case study, The propositus in Dallas was a 13-year-old 46,XY female with clitoromegaly, primary amenorrhea and undescended testes. An older 46,XY female sibling with clitoromegaly had undergone surgical repair in infancy. So, in fact, the literature attests the use of "46,XY female" to describe how patients present before any surgical intervention is planned. (It's also found in papers that are less suitable from the standpoint of preferring reviews, but maybe still worth noting; e.g., describing patients as 46, XY female with virilization in puberty [16].) Overall, the terminology appears to be a bit of a mess, which is all the more reason for us to go for the most specific options available. XOR'easter (talk) 20:05, 15 July 2021 (UTC)

I did say "representative", as it is natural to discuss sex differences in virtually any disease. Phrases like "affected males", "male limited" and "female" are easily found in their usual meanings (sex) particularly when discussing 5ARD. I've presented high quality, highly cited reviews that focus on the 5ARD specifically. Even in at least one of your sources you can see "affected males". If you assess the cites and focus of some of your sources (e.g, opinion article "Is there a role for 5α-reductase inhibitors in transgender individuals?"), you can see that they aren't really comparable to reviews that are talking specifically about 5ARD. "Karyrotypic males" is right out, that qualifier is only used in the context of discussing other aneuplodies, we don't qualify sex differences in this way since almost all males are "karyotypic" (and we can find RS that show 5ARD can affect males who are not karyotypic). Case studies that use "XY female" are very very confusing, consider WP:UBO when using terminology from case studies (they are generally not highly cited). Maneesh (talk) 21:16, 15 July 2021 (UTC)

"46,XY female" did not come from a primary write-up of a case study, but from the Mendonca et al. (2016) review to which you pointed (section 1.2; see also section 7.1). I don't think we can exclude "karyotypic" out of hand, since the literature does use it (some examples quoted here), and if the question is how to introduce the topic, then it makes sense to start with how the condition may present in 46,XY individuals — the most common and most heavily covered case — before moving on to other variations. XOR'easter (talk) 21:11, 16 July 2021 (UTC)

My mistake, I suspect Mendonca is carefully referring to what the underlying 1974 case study says (using the word "propositus") which I do not have access to. If you look at Medonca's language throughout the review:

• "Most affected males are raised as females..."
• "Fertility can be achieved in some affected males..."
• "An autosomal recessive disorder of sex development (DSD) in males termed pseudovaginal perineoscrotal hypospadias was described in 1961 by Nowakowski and Lenz [9]. The main feature of this syndrome was that affected males presented with female external genitalia but bilateral testes and male urogenital tracts in which the ejaculatory ducts terminate in a blind-ending vagina."
• "Facial and body hair is decreased in comparison with unaffected males, but male pattern baldness does not occur in 5areductase type 2 deficiency."
• "Affected males are as tall as their unaffected brothers..."
• "Gynecomastia is only rarely observed in males with 5a-reductase type 2 deficiency..."
• "Facial and body hair is decreased in comparison with unaffected males..."
• "The diagnosis is usually made at birth, infancy or at puberty. In the newborn, the features of 46,XY DSD due to 5a-reductase type 2 deficiency overlap with other forms of male DSD such as androgen insensitivity syndrome..."
• "Most males with 5a-reductase type 2 deficiency are raised in the female social sex."
• "Testicular descent through the inguinal canal is generally arrested in males with 5a-reductase type 2 deficiency."
• "The germ cell population is normal in males with 5a-reductase type 2 deficiency..."
• "In the 40 years since it was established that impairment of dihydrotestosterone formation is the cause of a specific, autosomal recessive male disorder of sexual development."
• "The correct and early diagnosis is important to suggest the male sex as the sex of rearing."
• "Affected males can occasionally have children..."

I think it's rather clear the authors know the only people that can have the severe presentation of 5ARD are males. The do sometimes use "male" and "female" unqualified to describe "social sex" but they are very clear in the context.Maneesh (talk) 03:23, 17 July 2021 (UTC)

The fact that the exact phrase "Genetic male" does not occur in a paper from 1996 (25 years ago!) is not important – especially since the very first sentence specifies "46,XY males". It sounds to me like they're talking about "genetic males". WhatamIdoing (talk) 02:02, 16 July 2021 (UTC)

WP:MEDDATE doesn't magically exclude a 1996 paper. As I've already explained, there isn't a huge amount of exciting research happening in 5ARD, most of the RS are older closer to the time when science was figuring out more of the details. The title of the paper makes it clear that both males and females can have the condition, representing the sex differences in presentation is what the RfC is about. Hard to do if you don't use the terms "male" and "female". Maneesh (talk) 03:20, 16 July 2021 (UTC)

The Azzouni review is largely about biochemistry rather than the condition, and it's published by Hindawi, which is on the Wikipedia:WikiProject Academic Journals/Journals cited by Wikipedia/Questionable1 list for needing a closer look – not an absolute strike against, and some of their journals are fine, but it's not exactly confidence-inspiring, either. WhatamIdoing (talk) 02:08, 16 July 2021 (UTC)

This particular review is fine, find one that is more recent and more highly cited and if you want (256 by google scholar). Read the review title: "The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases, this condition is *named* after its biochemical origin. There can't be much discussion about it without reference to biochemistry. Maneesh (talk) 03:05, 16 July 2021 (UTC)

The very first words in Mendonca are "46,XY due 5α-reductase type 2 deficiency subjects". That sounds like "genetic males". The abstract talks about "affected 46,XY individuals" before simplifying to "affected males". WhatamIdoing (talk) 02:16, 16 July 2021 (UTC)

But it clearly uses "affected males", i.e. males are the ones affected by the severe form of the condition. It does not use "genetic male". Maneesh (talk) 03:05, 16 July 2021 (UTC)

When you read Kang, the Clinical Presentation section says "The affected subjects are 46XY males with testes and male accessory ducts but predominantly female external genitalia." That sounds like "genetic males" to me. WhatamIdoing (talk) 02:17, 16 July 2021 (UTC)

46XY males are males, it certainly wouldn't make sense to use that term here since even though almost every male affected by 5ARD would be XY, RS report some that are not. Again, no occurrence of "genetic male".Maneesh (talk) 03:05, 16 July 2021 (UTC)

Maneesh, you have claimed that these sources don't describe the affected people beyond saying that they're "male", but that's not true. Three of these four sources specifically specify that they're talking about males with XY chromosomes. If even your chosen sources are doing this, shouldn't we? WhatamIdoing (talk) 02:20, 16 July 2021 (UTC)

You sure are finding "genetic male" in a lot of places where my eyes can't seem to! All of these sources use "male". It's pretty clear. The refined categories they use are sometimes understandable in the context of their specific discussions, but even you can see that sources can't help but use the simple and straightforward "male". Maneesh (talk) 03:05, 16 July 2021 (UTC)

...but even you can see that...

Mathglot (talk) 11:41, 16 July 2021 (UTC)

In this context, "male" is not simple or straightforward. That's kind of the whole problem. It costs us very few additional words to be very much more specific and clear. If we can't discuss the condition without reference to biochemistry, then we're committed to jargon already; why not say "genetic" or "karyotypic" or "46, XY"? XOR'easter (talk) 20:17, 16 July 2021 (UTC)

In this case it is simple and straightforward, 5ARD males can only have the potential to produce sperm and not ova, they are male. What does being overly specific offer? You would define the sex differences between "genetic males" and "females"...what set of people is left over then? Look at a highly cited (300+) review source that does use "genetic male" once:

• "The facial and body hair is decreased, and male pattern baldness has never been observed in genetic males with this condition..."

ok...but look at all the sentences that are much clearer (I am ignoring the many instance of phrases like "male sexual differentiation" which can only happen in males):

• Title: "Androgens and male physiology the syndrome of 5a-reductase-2 deficiency"
• "The clinical, biochemical and molecular genetic analyses of 5a-reductase-2 deficiency highlight the significance of DHT in male sexual differentiation and male pathophysiology"
• "In humans, with the onset of puberty, the affected males have increased muscle mass and deepening of the voice..."
• "Affected males in these kindreds are as tall as their unaffected siblings..."
• "...the prostate in the affected male adults is nonpalpable"
• "...prostate hyperplasia have not been reported in affected males."
• For females: "Homozygous females with a 5a-reductase-2 gene mutation and decreased plasma DHT appear to have decreased body hair and delayed menarche but normal to enhanced fertility."

Source seems pretty clear as to what term it is using when describing which set of people this disease affects: males. They are the only clear category of people who produce sperm, who have prostrates, etc. that is why this is condition is about male pathophysiology. You can see the same in other high quality sources that focus on this condition for obvious reasons. Maneesh (talk) 22:13, 16 July 2021 (UTC

The abstract to that review says, The affected 46XY individuals have high normal to elevated plasma testosterone levels with decreased DHT levels and elevated testosterone/DHT ratios. It seems that they regard "46XY individuals" as the most succinct way to introduce the class of affected individuals they're writing about. If the question is how to write the opening lines of the article text, that would be the relevant example to follow. XOR'easter (talk) 16:38, 17 July 2021 (UTC)

If your claim is that because the abstract uses a term first means it is high priority, surely using "male" in the *title* (and not 46XY individuals") certainly even higher priority. Maneesh (talk) 02:54, 18 July 2021 (UTC)

OMIM is also WP:RS (the OMIM number should be on this page). You can see from from the entry there is no occurrence of "genetic male". Same idea:

• "...PPSH is a male-limited..."
• "The affected males were born with ambiguous genitalia..."
• "However, a deficiency in dihydrotestosterone production not only impairs differentiation of male external genitalia but also affects the development and secretory function of the prostate and seminal vesicles."
• One instance of "46,XY males show ambiguous genitalia at birth,", I can see why they might want to emphasize that this condition is not dependent on aneuploidy at the outset.

Maneesh (talk) 22:20, 16 July 2021 (UTC)

The instance of "46,XY males" occurs in the first sentence of their "Description" section (the second sentence of the page overall). If the question is how we should write the opening lines of the article, that would again suggest that "46,XY" is the way to go. Of course, later in the article, we could rely more on context, but the RfC points to the first sentence of "Signs and symptoms", where being specific matters the most. XOR'easter (talk) 16:43, 17 July 2021 (UTC)

You should also consider that the title of the OMIM article being with "pseudovaginal.." which is the phenotype; in that case it is important to be clear right away that these are normal males genetically. The title of this article is the enzyme deficiency. You aren't buying any specificity with "46, XY", the OMIM entry is just making it clear we are talking about plain old males genetically. This isn't even quite correct given the recent report of XYY and 5ARD. Maneesh (talk) 02:07, 18 July 2021 (UTC)

I was summoned to the first RFC by a bot, and I've been following the discussion since then. I find myself agreeing with XOR'easter and others that we should go with "genetic," "karyotpic," or "46, XY." Enough sources use similar language and there's no reason that we shouldn't be more precise. ScottishFinnishRadish (talk) 20:24, 16 July 2021 (UTC)

• Neutral about using "genetic males" first, but use "males" at least most of the time thereafter for simplicity. That seems to follow the sources quoted above, which mostly use "male" for simplicity, but do occasionally specify further. We certainly don't need to say "genetic male" over and over once it's established that is what is meant; sources definitely don't. I oppose "karyotypic male" or "46,XY male" as this is WP:JARGON to most people. Crossroads ^-talk- 06:05, 17 July 2021 (UTC)

That's a fair point, but when the article title has an enzyme with a Greek letter in it, I wonder if we haven't already lost the jargon battle before it started. And, per WP:ONELEVELDOWN, the relevant audience might plausibly be expected to have enough background to know what X and Y chromosomes are (that's, what, ninth-grade biology in America?). XOR'easter (talk) 16:38, 17 July 2021 (UTC)

I tend to agree with Crossroads: we don't need to specify "genetic male" (or any other clarifying term) every single time. Definitely in the lead, and then the first reasonable opportunity should normally be enough. WhatamIdoing (talk) 21:28, 17 July 2021 (UTC)

Also, we'll need to use similar clarifying language around "females", since most "genetic males" have been raised as girls and believed themselves to actually be female. WhatamIdoing (talk) 21:35, 17 July 2021 (UTC)

Do you have a source for the claim that most genetic males believe themselves to be females? Edit: Almost all males are genetic males so this is very difficult to believe. Maneesh (talk) 01:51, 18 July 2021 (UTC)

Presumably she meant most genetic males with this condition. Crossroads ^-talk- 03:11, 18 July 2021 (UTC)

What is the difference between the set of "genetic males with this condition" and "males with this condition" then? They look like the same set except perhaps SRY-ve XX males with 5ARD (of which there are no known reports, and would certainly be extremely rare). 05:19, 18 July 2021 (UTC)

If you don't understand this, then you shouldn't be editing this page. Trankuility (talk) 07:10, 18 July 2021 (UTC)