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Glossary

Partial AIS

[last updated 14 Oct 2009]

Introduction

This page considers the partial forms of AIS (PAIS).

Until about 10 weeks gestational age, male and female embryos appear identical in external anatomy. The same structures then begin to differentiate as male under the influence of testosterone, or as female if the influence of testosterone is absent. In the presence of intermediate amounts of androgens, or partial sensitivity to androgens, the external genitals will develop in an in-between way. In PAIS, the external genitalia can therefore be ambiguous, that is, intermediate in structure between male and female. Note that the structure of ambiguous external genitalia can be the same, whether the genetic sex and the sex of the gonads is male or female. The structure of the external genitals does not provide a way to determine whether the condition is PAIS or some other intersex condition.

For an introduction to the AIS grading scale, which runs from Grade 1 (i.e. male with 'mild PAIS') to Grade 7 (i.e. CAIS female with complete insensitivity) see What is AIS?. The term 'severe PAIS' is sometimes used to refer to Grades 5 and 6, to distinguish them from the lower grades of PAIS.

Grades of Partial AIS

In AIS Grades 5 and 4, the clitoris is enlarged. In Grade 5, there may be partial fusion of the labia majora (outer vaginal lips), in which the posterior (back) portion of the labia form a web of tissue across the back part of the vaginal outlet. In Grade 4, this fusion extends further forward, covering both the vaginal opening and the true urethral opening. The cavity formed by the fused labia, through which urine exits, is called a urogenital sinus.

The labial fusion can be surgically divided, making the vaginal opening accessible for pressure dilation (a non-surgical way of lengthening the vagina). This division is a relatively minor operation, and is unlikely to adversely affect erotic sensitivity, but it should be performed by a physician familiar with this type of surgery. Vaginal dilation can be successful in Grade 4 AIS, and should always be attempted before surgical vaginoplasty is planned.

In Grade 3 and the more masculinized form of Grade 4, the labia are completely fused, so that the urethral opening is at the base of the clitoris/penis. The fused labia may have a rugose, or wrinkled appearance and form a bifid, or double, scrotum. The fusion is then more properly called 'labio-scrotal fusion'. The phallus has the appearance of a large clitoris, or a small, bent, penis, bound down in structures called chordee. The chordee is formed from the same tissues that form the labia minora in the female and the frenulum of the penis and the tissues surrounding the urethra (corpus spongiosum) on the underside of the penis in the male. It is not true that the presence of chordee makes erections painful.

In Grade 2, the genital appearance is that of a male with hypospadias, that is, with a urethral opening located somewhere on the underside of the penis. There may be an open gutter running from the urethral opening to the glans of the penis.

Note: Hypospadias not in itself an intersex condition but is a congenital condition of the penis which is fairly common, affecting approximately in every 200 male births. It can be present in some cases of intersex (e.g. PAIS Grades 2 and 3). The urethra (the tube through which urine is expelled) fails to grow right through to the tip of the penis; instead, it opens on the underside, somewhere further back than is usual. In some cases, the opening may be at the base of the penis, or back on the scrotum, and the penis might be curved downward. See Links to Other Sites for more information, including a support group for this specific problem.

The hypospadias can be corrected surgically by creating an extension of the urethra on the penis with skin grafts. The benefit of this surgery is to make urination possible in a standing position. Drawbacks include constriction of the constructed urethra requiring dilation, and a greater risk of urinary tract infections. This surgery may also lead to a urinary outlet that is irregular in shape, causing unhygienic spraying of urine.

Investigations in PAIS

There are other conditions, apart from AIS, that will produce the same type of genital 'deformity' in a genetic male, but the body's sensitivity to androgens can be tested in infancy by applying testosterone ointment to the pubic region. If no response, or only a weak response to the hormone is observed, then the baby has PAIS, and a female assignment should be more strongly considered. At puberty, the patient will probably develop breasts and be unable to virilize completely. Also, the phallic enlargement that normally occurs at puberty may not occur, so that a penis that is marginal in size will remain so.

X-ray studies involving the radio-opaque dye injected into the urogenital sinus can be used to determine the extent of development of the vagina. The vagina and labia minora may be fairly well-developed, but not evident on external examination due to labial fusion.

Sex of Rearing in PAIS

The decision regarding the sex of rearing of a baby with PAIS should be made according to the individual's best interests, numerous factors such as sexual functioning, how the individual would feel about themselves need to be considered, preferably with less emphasis on surgery, even perhaps minimalising the need for surgery. Puberty is another issue that should be considered. While many would feel comfortable with a puberty that is concordant with the assigned gender of rearing, some would not; and an understanding of the individual's wishes should take priority. The best approach really is to explain the situation, let the patient decide what is best for them, and offer the best choices available. Patients with Grades 3-7 AIS are always sterile, so potential fertility should not be a consideration.

There are forms of PAIS with a male phenotype and minimal (Grade 2) or no (Grade 1) genital 'deformity'. In these cases, gender assignment is nearly always male, and the androgen insensitivity is only detected at puberty when breast development (gynecomastia) occurs. The patient may be infertile.

Patients with Grade 5, and most with Grade 4, PAIS are too unresponsive to androgens to undergo a masculinizing puberty, either spontaneously or under the influence of exogenous hormones, and cannot be masculinzed surgically so as to function sexually as males. Like patients with CAIS, they will undergo a spontaneous feminizing puberty, and should be raised as females.

In PAIS Grade 3 (and some with Grade 4), there may be controversy about whether to raise the baby as a male or as a female.

Treatment in PAIS

Treatment of patients with PAIS raised as females is similar to that of patients with CAIS. Fused labia can be divided surgically to exteriorize the vaginal opening. Removal of an enlarged clitoris is controversial because of the potential for loss of sexual sensitivity, although many patients who have undergone clitoridectomy report orgasms. An operation called "clitoral recession" makes the clitoris less prominent while preserving most of its tissue, and is claimed to have less effect on sensitivity. See also Genital Surgery.

Gonadectomy before puberty, with puberty induced by hormone replacement is sometimes recommended to prevent pubertal virilization in patients with PAIS raised as females. It should be remembered, however, that in Grades 3 and 4 PAIS, the observed effects of androgens are very weak and pubertal effects are about what is seen in normal females.

Patients with PAIS raised as males usually have masculinzing genital surgery (urethroplasty of the hypospadiac penis to make urination in a standing position possible). If prominent breasts develop at puberty, they can be removed (mastectomy). Hormone replacement with androgens may not result in full development of male secondary sex characteristics such as beard growth or deepening of the voice.

Issues/Support for 'Severe PAIS'

Women at the higher grades of PAIS and born with an essentially female genital anatomy are invited to contact one of the AIS groups listed on the How to Contact Us page.

Issues/Support for 'Mild PAIS'

Support for people with 'mild PAIS' (i.e. at the lower end of the grading scale) having a male or female gender ID is available as follows:

Female Gender ID

[Information on the relevant issues - to be provided]

Contact 1
A contact (L. C.) who has Grade 1 PAIS told us (Jan 2001) that she was willing to help people in the lower grades of PAIS who identify as female. She told us:

I'm female but was raised as male until I was 18, when I transitioned to female, but haven't had any operations etc. I'm 24 now and I've been living female for the last 6 years or so - I changed over when I went to university. At the time I changed over, the lack of much going on puberty-wise was a bit of a godsend - no beard to worry about etc :), but now I'm wondering what exactly I am, as I feel more androgynous really.

In mid Feb 2001 she wrote again:

I saw [Dr.] Cathy M[into], and while I'm not right for her project [see Research Studies page] I do look [to be] intersexed, with PAIS looking most likely. I've just got my doctor to arrange for me to be referred down there to [Dr.] Gerard Conway for a thorough prod and poke.[....] Funnily enough, since I've started investigating and chatting about this with friends etc., I've found an awful lot more people who also have the same doubts who are also very confused. There seem to be a lot more of us out there than I thought :) Anyway, I can't tell you how grateful I am for your help - putting me in contact with the right people etc.

In mid-April she told us:

(just got my diagnosis - I do have PAIS :)

We asked: "Congrats on getting a diagnosis. Was it the boys and girls at UCL/Middlesex Hospitals, London, who helped you with that or somewhere else?"

It was indeed - we were thinking that as I've been on hormones for ages with TS stuff that I'd have shut down any testosterone production, but despite being on twice the normal amount of oestrogen I'm still pumping the stuff out. My god - I'd have been Tom Jones if I wasn't insensitive to the stuff :) I'll have to learn to wiggle my hips just in case. Anyhows, that rather proves I can make testosterone, so I must be insensitive to it :)

She set up two discussion groups:

http://groups.yahoo.com/group/pais-male

http://groups.yahoo.com/group/Intersex-United-Kingdom (may not be operating now)

She has now stopped being a contact point, in order to concentrate on other things in her life, and these groups are being run by Michelle (Contact 2, below).

Contact 2
Those with 'mild PAIS' assigned and reared male (but who may now have a female gender ID) may also contact Michelle who, like L.C., has been working with us for some time and who told us (Feb 2003):

I have set up a Testicular Dysgenesis Syndrome (TDS) support network (http://groups.yahoo.com/group/TDS_Network/files/tds_network.htm) having identified a need following a recent meeting at the Academy of Medical Sciences (http://www.acmedsci.ac.uk/20030124abstracts.htm). The network to support those males affected by TDS as a syndrome first described by Prof. Neils Skakkebaek in his 2001 paper (www.ourstolenfuture.org/NewScience
/reproduction/TDS/2001skakkebaeketal.htm
).


It is here to campaign for an approach to treatment that involves a team approach to a set of symptoms that represent a syndrome with common origin, rather than [in contrast to] the current state of affairs, which may entail a lack of diagnosis, and treatment by a number of specialists whose only communication is via the patient and their body [i.e doctors not sharing knowledge with each other].

It is also here to assist existing intersex networks - by creating somewhere that adult males, who believe that they have some such symptoms and may be intersex, can be pointed to in their search for help and answers - should such organisations feel unable to assist. It will also build as a support network for those in the UK affected by the syndrome.

Michelle told us (Feb 2008):

I closed down the TDS site, as it was very quiet. I still have access to the 'PAIS-male' site, and believe that L. has given me privileges to help manage it as she has moved on. That is still quiet as well, but worth a post as there are people who seem to keep an eye on posts. I am involved with OII (UK) (http://www.intersexualite.org/Index.html) along with S_____ (as UK board members), and that is certainly a place people can go, as we now have a couple of forums. It is intended to be inclusive, regardless of IS condition or diagnosis, and is accepting of IS people with a trans-like history as well as trans people with an IS-history.

Other discussion groups:

http://groups.yahoo.com/group/intersex-androgynous (has 342 members and has been running since 1999, with 6,800 archived posts as of Sept 2001)

http://groups.yahoo.com/group/Intersexed_Society

Male Gender ID

[Information on the relevant issues - to be provided]

People with 'mild PAIS' who have concerns particular to a male phenotype and/or role need to be aware that our organisation is run by women and has evolved to-date predominantly as a women's group. We have provided phone support and general information to a number of PAIS men over the years and offered them all the benefits of membership, but have only ever had a few male subscribers. We have tried to encourage these, and other male enquirers, to get together and develop a full support function for men, either as part of AISSG or separately, but this has not really got off the ground as yet. We would welcome an expansion of facilities in this direction.

In the meantime, the following people have offered to help with specific areas:

Contact 1 (medical aspects, G.I. issues, PAIS children)

A PAIS man (J.) has offered to provide advice and support in the following areas:

The UK support group can pass on enquiries to the above contact.

Contact 2 (male fertility)

We were contacted in early 2001 by a PAIS man (G.) who told us:

There have been a few cases of PAIS being treated by giving high doses of testosterone, i.e. 250 mg weekly for about 3 yrs. This only treats the secondary male characteristics but not the fertility. For the fertility, the treatment is similar to the treatment of hypogonadotrophic hypogonadism (except that we have hypergonadotrophic hypogonadism). This treatment has to be slightly modified. AIS is unlike other intersex groups since everthing else is normal except that the androgen receptors have mutated. But somehow they do respond to high levels of testosterone. So our group of unfortunate human beings have some hope.

I have been married for 5 yrs. There were no children so the pressure was great. I did a lot of research on my own. [The] past 2 yrs I have been trying a lot of drugs. I was azoospermic [no mature sperm produced] but a testicular biopsy showed immature sperms. After trying various drugs, I managed to produce normal sperms. In August 2000, I made history by producing the first embryo by a PAIS victim. Using ICSI [Inter-Cytoplasmic Sperm Inoculation - see Fertility Advances] we obtained 3 embryos. Only 1 was normal. This was implanted in my wife. Unfortunately this was rejected. I was very disappointed, after so much of effort, it was not an easy task.

The above contact sent us (Aug 2002) the reference to the paper by Weidemann et al (see General Refs below) saying:

Please take note of this abstract and note it down in your website [because] most people are looking for treatment. This does not work for everyone. It works for only certain mutations. Therefore it is always advisable to do a genetic diagnosis at the molecular level.

He is willing to answer enquiries concerning male infertility via paisman@hotmail.com.

Contact 3 (general male PAIS issues)

The program director of the group listed under 'East Africa' on our How to Contact Us page is a PAIS man who offered to help an enquirer who was having trouble masculinising on testosterone. So he might be a source of general help and advice.


Note: The list below contains references to medical journal articles/papers relevant to the subject matter of this web page. We don't expend as much effort keeping this list updated as we do for those on other pages (covering topics like facing the daignosis, vaginal hypoplasia, the pros and cons of gonadectomy and genital surgery) because medical articles covering clinical features, genetics etc. are not as useful to patients/parents as those covering practical issues and dilemmas.

General Refs:

See Medical Literature Sites on our 'Links to Other Sites' page for ways of accessing journal articles.

Money, J., Biographies of Gender and Hermaphroditism in Paired Comparisons, Elsevier, ISBN 0-444-89129-3, Chapters 2 and 5

Money, J and Onguro, C. (1974) Behavioral Sexology: Ten cases of genetic male intersexuality with impaired prenatal and pubertal androgenization. Arch. Sex. Behav., 3: 181-205

Quigley et. al., Androgen Receptor Defects: Historical, Clinical, and Molecular Perspectives, Endocrine Reviews, Vol. 16, No. 3. June 1995

Quigley CA, French FS. Androgen insensitivity syndromes. In: Current Therapy in Endocrinology and Metabolism, 5th edition. Editor W Bardin. Mosby-Year Book Inc., 1994, pp. 342-354.

Costa et. al., Managment of ambiguous genitalia in pseudohermaphrodites: new perspectives on vaginal dilation, Fertility and Sterility, Vol. 67, No. 2, Feb. 1997.

Weidemann W, Peters B, Romalo G, Spindler KD, Schweikert HU. Response to androgen treatment in a patient with partial androgen insensitivity and a mutation in the deoxyribonucleic acid-binding domain of the androgen receptor. J Clin Endocrinol Metab 1998 Apr; 83(4):1173-6.


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