Editing 5α-Reductase 2 deficiency (section)

==Management==
One of the most clinically challenging and controversial topics with 46,XY DSD is the practice of "sex assignment" or "sex of rearing".<ref name="Byers2017">{{cite journal |last1=Byers |first1=Heather M. |last2=Mohnach |first2=Lauren H. |last3=Fechner |first3=Patricia Y. |last4=Chen |first4=Ming |last5=Thomas |first5=Inas H. |last6=Ramsdell |first6=Linda A. |last7=Shnorhavorian |first7=Margarett |last8=McCauley |first8=Elizabeth A. |last9=Amies Oelschlager |first9=Anne-Marie E. |last10=Park |first10=John M. |last11=Sandberg |first11=David E. |last12=Adam |first12=Margaret P. |last13=Keegan |first13=Catherine E. |title=Unexpected ethical dilemmas in sex assignment in 46,XY DSD due to 5-alpha reductase type 2 deficiency |journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics |date=June 2017 |volume=175 |issue=2 |pages=260–267 |doi=10.1002/ajmg.c.31560|pmid=28544750 |pmc=5489130 }}</ref> This is especially so in 5αR2D, since most affected individuals have undervirilized genitalia at birth but virilize to varying degrees at puberty. Historically most 5αR2D individuals have been "raised as females",<ref>{{cite journal |last1=Kolesinska |first1=Z |last2=Ahmed |first2=SF |last3=Niedziela |first3=M |last4=Bryce |first4=J |last5=Molinska-Glura |first5=M |last6=Rodie |first6=M |last7=Jiang |first7=J |last8=Sinnott |first8=RO |last9=Hughes |first9=IA |last10=Darendeliler |first10=F |last11=Hiort |first11=O |last12=van der Zwan |first12=Y |last13=Cools |first13=M |last14=Guran |first14=T |last15=Holterhus |first15=PM |last16=Bertelloni |first16=S |last17=Lisa |first17=L |last18=Arlt |first18=W |last19=Krone |first19=N |last20=Ellaithi |first20=M |last21=Balsamo |first21=A |last22=Mazen |first22=I |last23=Nordenstrom |first23=A |last24=Lachlan |first24=K |last25=Alkhawari |first25=M |last26=Chatelain |first26=P |last27=Weintrob |first27=N |title=Changes over time in sex assignment for disorders of sex development. |journal=Pediatrics |date=September 2014 |volume=134 |issue=3 |pages=e710-5 |doi=10.1542/peds.2014-1088 |pmid=25092939|s2cid=9316947 }}</ref> but later reports show that over half of patients who underwent virilizing puberty adopted a male gender identity thus challenging historical practices.<ref>{{cite journal |last1=Cohen-Kettenis |first1=PT |title=Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. |journal=Archives of Sexual Behavior |date=August 2005 |volume=34 |issue=4 |pages=399–410 |doi=10.1007/s10508-005-4339-4 |pmid=16010463|s2cid=146495456 }}</ref><ref>{{cite journal |last1=Costa |first1=EM |last2=Domenice |first2=S |last3=Sircili |first3=MH |last4=Inacio |first4=M |last5=Mendonca |first5=BB |title=DSD due to 5α-reductase 2 deficiency&nbsp;— from diagnosis to long term outcome. |journal=Seminars in Reproductive Medicine |date=October 2012 |volume=30 |issue=5 |pages=427–31 |doi=10.1055/s-0032-1324727 |pmid=23044880|s2cid=5289961 }}</ref><ref>{{cite journal |last1=Maimoun |first1=L |last2=Philibert |first2=P |last3=Cammas |first3=B |last4=Audran |first4=F |last5=Bouchard |first5=P |last6=Fenichel |first6=P |last7=Cartigny |first7=M |last8=Pienkowski |first8=C |last9=Polak |first9=M |last10=Skordis |first10=N |last11=Mazen |first11=I |last12=Ocal |first12=G |last13=Berberoglu |first13=M |last14=Reynaud |first14=R |last15=Baumann |first15=C |last16=Cabrol |first16=S |last17=Simon |first17=D |last18=Kayemba-Kay's |first18=K |last19=De Kerdanet |first19=M |last20=Kurtz |first20=F |last21=Leheup |first21=B |last22=Heinrichs |first22=C |last23=Tenoutasse |first23=S |last24=Van Vliet |first24=G |last25=Grüters |first25=A |last26=Eunice |first26=M |last27=Ammini |first27=AC |last28=Hafez |first28=M |last29=Hochberg |first29=Z |last30=Einaudi |first30=S |last31=Al Mawlawi |first31=H |last32=Nuñez |first32=CJ |last33=Servant |first33=N |last34=Lumbroso |first34=S |last35=Paris |first35=F |last36=Sultan |first36=C |title=Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients. |journal=The Journal of Clinical Endocrinology and Metabolism |date=February 2011 |volume=96 |issue=2 |pages=296–307 |doi=10.1210/jc.2010-1024 |pmid=21147889|doi-access= }}</ref>

The goal of sex assignment/rearing is to facilitate the greatest likelihood of concordant gender identity in the patient's adulthood. The factors that contribute to gender identity are complex and not easy to report but some factors that contribute include sex chromosomes, androgen exposure, psychosocial development, cultural expectations, family dynamics, and social situation.<ref name="Byers2017"/>

Female sex rearing in 5αR2D individuals involves surgical procedures such as childhood gonadectomy (to prevent virilization at puberty) and vaginoplasty.<ref name="Cheon2011"/> Life-long hormonal treatments as also required for the development and maintenance of female secondary sex characteristics.<ref>{{cite journal |last1=Hughes |first1=IA |last2=Houk |first2=C |last3=Ahmed |first3=SF |last4=Lee |first4=PA |last5=Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus |first5=Group. |title=Consensus statement on management of intersex disorders. |journal=Journal of Pediatric Urology |date=June 2006 |volume=2 |issue=3 |pages=148–62 |doi=10.1016/j.jpurol.2006.03.004 |pmid=18947601}}</ref> Male sex of rearing avoids lifelong hormonal treatments and allows for the potential of fertility.<ref name="Byers2017"/>  [[Cryptorchidism]] and hypospadias must be addressed to prevent damage to the seminiferous tubules that are essential for spermatogenesis and fertility.<ref>{{cite journal |last1=Nordenskjöld |first1=A |last2=Ivarsson |first2=SA |title=Molecular characterization of 5 alpha-reductase type 2 deficiency and fertility in a Swedish family. |journal=The Journal of Clinical Endocrinology and Metabolism |date=September 1998 |volume=83 |issue=9 |pages=3236–8 |doi=10.1210/jcem.83.9.5125 |pmid=9745434|doi-access=free }}</ref> Some approaches encourage a diagnosis during infancy prior to any gender assignment or surgical interventions.<ref name="Cheon2011"/>

The intersection of the child's well-being, parental wishes, recommendations of the associated medical team, and local laws makes decision-making challenging in these cases. The necessity and ethics around consent and deception involved in administering such interventions have been seriously questioned.<ref>{{cite journal |last1=Dreger |first1=Alice Domurat |title="Ambiguous Sex": Or Ambivalent Medicine? Ethical Issues in the Treatment of Intersexuality |journal=The Hastings Center Report |date=May 1998 |volume=28 |issue=3 |pages=24–35 |doi=10.2307/3528648|jstor=3528648 |pmid=9669179 }}</ref>

Assisted reproduction methods involving sperm extraction and concentration for [[intrauterine insemination]],<ref>{{cite journal |last1=Katz |first1=Melissa D. |last2=Kligman |first2=Isaac |last3=Cai |first3=Li-Qun |last4=Zhu |first4=Yuan-Shan |last5=Fratianni |first5=Carmel M. |last6=Zervoudakis |first6=Ioannis |last7=Rosenwaks |first7=Zev |last8=Imperato-McGinley |first8=Julianne |title=Paternity by Intrauterine Insemination with Sperm from a Man with 5α-Reductase-2 Deficiency |journal=New England Journal of Medicine |date=3 April 1997 |volume=336 |issue=14 |pages=994–998 |doi=10.1056/NEJM199704033361404|pmid=9077378 |doi-access=free }}</ref> [[intracytoplasmic sperm injection]],<ref>{{cite journal |last1=Matsubara |first1=Keiko |last2=Iwamoto |first2=Hideki |last3=Yoshida |first3=Atsumi |last4=Ogata |first4=Tsutomu |title=Semen analysis and successful paternity by intracytoplasmic sperm injection in a man with steroid 5α-reductase-2 deficiency |journal=Fertility and Sterility |date=December 2010 |volume=94 |issue=7 |pages=2770.e7–2770.e10 |doi=10.1016/j.fertnstert.2010.04.013|pmid=20493473 |doi-access=free }}</ref> and [[in vitro fertilization]]<ref>{{cite journal |last1=Kang |first1=Hey-Joo |last2=Imperato-McGinley |first2=Julianne |last3=Zhu |first3=Yuan-Shan |last4=Cai |first4=Li-Qun |last5=Schlegel |first5=Peter |last6=Palermo |first6=Gianpiero |last7=Rosenwaks |first7=Zev |title=The first successful paternity through in vitro fertilization–intracytoplasmic sperm injection with a man homozygous for the 5α-reductase-2 gene mutation |journal=Fertility and Sterility |date=May 2011 |volume=95 |issue=6 |pages=2125.e5–2125.e8 |doi=10.1016/j.fertnstert.2011.01.121|pmid=21334614 |doi-access=free }}</ref> have all demonstrated successful outcomes for fertility in those with 5αR2D.