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Glossary

Complete AIS

[last updated 08 June 2006]

Introduction

This page considers the Complete form of AIS (CAIS).

The clinical findings originally noted by Morris, who first assigned the name Testicular Feminization Syndrome (Testicular Feminisation Syndrome) to the condition (now replaced by the more accurate and, as far as most AIS women are concerned, much less stigmatizing term Androgen Insensitivity Syndrome), were as follows:

Morris's original patient had what is now termed Complete AIS (CAIS). The older literature often refers to this form of the condition as "classical testicular feminization syndrome". See Medical Textbooks Discussion and Terminology Debate on our Debates/Discussions page for some discussions amongst AIS women on the terminology used for AIS in medicine.

Even in CAIS there will be no ovaries, Fallopian tubes or uterus; and the vagina will be blind-ending and possibly short or absent. Female pubertal development occurs but there will be no menstruation and no possibility of conceiving/bearing children (although genetic advances in infertility treatment are occurring quite rapidly, see Fertility Advances).

Some girls with AIS may develop some dark, coarse pubic/underam hair (AIS Grade 6) but usually this does not develop (Grade 7) because its growth is dependent on the effects of androgens. The nipples usually remain under-developed and pale in colour. The vagina may need to be lengthened or constructed before sexual intercourse is possible (see Vaginal Hypoplasia).

The undescended testes can result in an inguinal hernia in infancy and this is when AIS may be diagnosed in an apparently female child (approx. 50% of cases). Otherwise CAIS may not be discovered until puberty when there is a failure to menstruate (approx. 50% of cases). Failure to menstruate is known as amenorrhoea (UK spelling)

The older literature sometimes states that girls with AIS are often tall, that the body form is "voluptuously female", i.e. with very adequate breast development, and that the skin maintains a good condition, not being prone to acne (which is linked to the effects of male hormones).

Pubic and Underarm (Axillary) Hair in AIS

Quigley et al draw attention to the question of pubic and axillary hair in AIS. They say:

Often the pubic hair in individuals with CAIS is reported as 'scanty' or 'sparse', and it is unclear whether the hair that is present is anything more than the vellus down (which is not androgen-dependent) similar to that found elsewhere on the body in both sexes, at all ages. True sexual hair - the longer, coarser, darker terminal hair characteristic of adult pubic and axillary regions - results from androgenic stimulation of hair follicles. The term pubic hair should therefore be confined to hair that is truly androgenic in nature, however sparse or abundant, and its distribution should be described in terms of Tanner staging.

Some individuals, considered in infancy to have the complete form of AIS, develop sexual hair at puberty, sometimes of the density and distribution seen in the normal postpubertal, 46,XX, female. The authors say that the presence of true pubic hair, even in an AIS individual with an entirely female phenotype, must be regarded as evidence for some degree of androgen responsiveness and that such individuals should be considered as having a severe partial form of AIS (Grade 6) rather than CAIS (Grade 7).

Changes at Puberty

Body Changes

Pubic and axillary hair growth is dependent on androgens. Even if the testes are still in place at puberty, pubic and axillary hair growth is likely to be sparse or absent.

Although androgens are often called "male hormones" and oestrogens are often called "female hormones," both types of hormones are present in males and females, just in different amounts. In normal males the body produces androgens and a smaller amount of oestrogens. In fact, the richest natural sources of oestrone (one type of oestrogen) is the testis of the stallion. Similarly, normal females produce male as well as female hormones. In AIS the testicular oestrogen is secreted in a non-cyclical manner and not cyclically as in the menstruating female.

In AIS, although the body is insensitive to androgens, it is very responsive to oestrogens, and is affected by the small amount of oestradiol (an oestrogen) produced by the testes, by the oestrone produced from testosterone in fat tissue, or by the oestrogen replacement therapy given in the case where the testes have been removed.

This means that the body not only fails to develop masculinity but develops even further in a feminine direction, causing the body appearance to perfectly simulate an XX female, with female breast development. However, since there is no uterus, and no ovaries, there is no possibility of menstruation. Although a vagina of sorts may be present, as mentioned earlier, it is usually no more than a short blind pocket, and may require lengthening if intercourse is to be possible (see Vaginal Hypoplasia).

Sensitivity to Oestrogens

Zachmann et al have studied growth in nine girls with AIS and suggest that girls with AIS may be more sensitive to the effects of oestrogens than normal females, because of their insensitivity to androgens. Unlike the situation in normal girls, the oestrogen effects are unopposed by the effects of the androgens from the adrenal glands and this could account for the very adequate breast development in AIS girls. A high sensitivity to very low quantities of oestrogens is also indicated by the observation by Sobrinho et al. of spontaneous breast development in patients with androgen insensitivity who have had gonadectomies. This increased sensitivity may have a bearing on the management of hormone replacement therapy (HRT) in these patients.

Growth - General

In the older literature it is often stated that girls with AIS are taller than average. Simpson states that individuals with CAIS are phenotypic females `with normal female appearance' and that their growth in stature and body proportions are normal but there are some observations indicating that they might be taller than normal females. The review of CAIS and PAIS by Griffin and Wilson mentions that AIS patients tend to have a masculine skeleton and that the size of their teeth is closer to that of men than of women. Dewhurst and Spence say that AIS subjects can show a eunuchoid appearance with elongated limbs and large hands and feet. An average height of 171.5 cm is given for a group of these patients by Varrela et al. A book chapter by Barlatos and Baramki gives an average height of 5 feet 7 and 1/2 inches. Zachman et al report the mean adult height in their AIS patients to be 172.3 cm, which was lower than normal men but higher than normal women.

Some of these observations, however, might have been made at a time when the practice of early gonadectomy and HRT was not so common and thus did not present a possible externally-applied growth regulating factor?

Growth - Role of Oestrogens

Ritzen has reviewed the field of pubertal growth in various genetic disorders, including AIS, and summarize the findings of Zachman et al and others. The latter authors point out that the normal male pubertal growth spurt can be quite satisfactorily explained by the combined action of testosterone and growth hormone, but that the mechanisms involved in the female growth spurt are not completely understood. Oestrogens had formerly been considered of minor importance, and in the growth of girls more influence had been attributed to androgens from the adrenal glands. Their studies suggest however that in normal girls the pubertal growth spurt results from the effects of oestrogens rather than adrenal androgens. They conclude that in AIS the following changes take place:

Presumably these observations were in the absence of any HRT and therefore in spite of plasma oestrogen concentrations that would tend to be lower (due to lack of ovarian oestrogens) than in normal girls of the same age. They suggest that girls with AIS are particularly sensitive to oestrogens (as evidenced also by their good breast development) because of lack of the counter-effect of androgens.

Growth - Role of Y Chromosome

Some researchers in the field have suggested that genes on the Y chromosome have an effect on growth, independently of hormonal changes, as shown by increased growth in boys with an extra Y chromosome. Westphal states that in AIS "the XY karyotype (chromosomes) will result in excessive final height in relation to the female phenotype (body form)". Varrela et al observed that the body shape (having accounted for size differences) of 46 XY females does not deviate much from that of normal females but that 46 XY females tend to be larger in all body measurements, although with a tendency to a slimmer body. The mean height (171.5 cm) of the 46 XY females was 10.2 cm higher than that of the normal females but was 4.9 cm lower than that of a sample of 40 normal males. They conclude that the Y chromosome has a direct influence on growth but that the greater height in normal males may indicate that an additive or inductive action of androgens is also necessary for the completion of body growth in normal males. They suggest that the body shape in 46 XY females is under the control of oestrogens and is not affected by the Y chromosome.


General Refs:

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

Quigley et al: Androgen Receptor Defects: Historical, Clinical and Molecular Perspectives. Endocrine Reviews, Vol. 16, No. 3, pp271-321 (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.

Morris J.M.: The syndrome of testicular feminization in male pseudo-hermaphrodites. Am. J. Obstet. Gynec. Vol 65, No. 6, 1192-1211, 1953.

Aona T., Mujake A., Kinugasa T., Kurachi K., Matsumoto K: Absence of positive feedback effect of oestrogen on LH release in patients with testicular feminization syndromes. Acta. Endocrinol. 87, 259-267, 1978.

Van Look P.F.A., Hunter W.M., Corker C.S., Baird D.T: Failure of positive feedback in normal men and subjects with testicular feminization. Clin. Endocrinol. 7, 353-366, 1977.

MacDonald P.C., Madden J.D., Brenner P.F., Wilson J.D., Siiteri P.K: Origin of estrogen in normal men and in women with testicular feminization. J. Clin. Endocrinol. Metab. 1979; 49:905-16.

Zachmann M., Prader A., Sobel E.H. et al: Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls. J. Paediatr. 1986:108:694-7.

Sobrinho L.G., Kase N., Grunt J.A: Spontaneous pubertal breast growth in a castrated patient with the syndrome of testicular feminization. Yale J. Biol. Med. 1971; 44:225.

Savage M. O: Endocrine studies in male pseudohermaphroditism in childhood and adolescence; Clin. Endocrinol. 1978; 8: 219 - 31.

Simpson J: Gonadal dysgenesis and abnormalities of human sex chromosomes: current status of phenotypic-karyotypic correlation. Birth Defects, Original Article Series, 11, 23-59, 1975.

Morris J.M. and Mahesh V. B: Further observations on the syndrome, `testicular feminization'. Am. J. Obstet. Gynec. Vol 87, No. 6, 731-748, 1963.

Smith D.W., Marokus R., Graham J.M: Tentative evidence of Y-linked satural gene(s). Clin. Pediatr. 1985;24:189

Griffin J.E., Wilson J.D: The androgen resistance syndromes: 5-alpha-reductase deficiency, testicular feminization syndrome and related disorders: in Stanbury J. B. et al, The Metabolic Basis of Inherited Disease; New York; McGraw Hill; 1083; pp 1919-1944, 1989.

Dewhurst C.D.; Spence J.E.H.: The XY Female. Br. J. Hosp. Med. 1977: 17: 498-506.

Varrela J., Alvesalo L., Vinkka H: Body size and shape in 46 XY females with complete testicular feminization. An. Hum. Biol. 1984;11:291 - 301.

Bartalos M., Baramki T. A: Medical Cytogenetics, Chap 12, Williams and Wilkins Co., Baltimore, Md., 1967.

Zachmann M., Prader A., Sobel E.H. et al: Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls. J. Paediatr. 1986:108:694-7.

Ritzen E.M.: Pubertal growth in genetic disorders of sex hormone action and secretion. Acta Paediatr. Suppl. 383: 22-5, 1992.

Zachmann M., Prader A., Sobel E.H. et al: Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls. J. Paediatr. 1986:108:694-7.

Ratcliffe S.G., Butler G.E., Jones M: Edinburgh study of growth and development of children with sex chromosome abnormalities. IV. Birth Defects 1990:26:1-44.

Westphal O: Tall Stature. Growth Matters Oct 1991 p6. Publishers Chapterhouse Codex Ltd.

Varrela J., Alvesalo L., Vinkka H: Body size and shape in 46 XY females with complete testicular feminization. An. Hum. Biol. 1984;11:291 - 301.

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

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

Groveman S: Medical, Psychological and Legal Issues in the Clinical Management of the Complete Androgen Insensitivity Syndrome Patient into Adulthood. A paper drafted in 1997 by Sherri Groveman who founded our sister group, AISSG US. It covers counselling, the clinical examination, truth disclosure, peer group support, vaginal construction, and gonadectomy and informed consent.

Ahmed S.F. et al: Phenotypic Features, Androgen Receptor Binding, and Mutational Analysis in 278 Clinical Cases Reported as Androgen Insensitivity Syndrome. J. Clin. Endoc. & Metab., Vol 85, No. 2, 2000.

Wisniewski A.B., Migeon C.J., Meyer-Bahlburg H.F.L., Gearhart J.P., Berkovitz G.D., Brown T.R., Money J: Complete Androgen Insensitivity Syndrome: Long-Term Medical, Surgical, and Psychosexual Outcome (or here). J. Clin. Endoc. & Metab., Vol. 85, No. 8, 2000.

Hines M., Ahmed F.S., and Hughes I.A: Psychological Outcomes and Gender-Related Development in Complete Androgen Insensitivity Syndrome. Archives of Sexual Behaviour, Vol. 32, No. 2, April 2003, pp. 93-101.

Minto C., Liao K., Conway G. and Creighton S: Sexual Function in Women with Complete Androgen Insensitivity Syndrome (or here). Fertility and Sterility, Vol. 80, No. 1, July 2003, pp 157 - 164.


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