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Hirsutism as a gynecologic problem
Hirsutism as a gynecologic problem S. LEON ISRAEL, M.D. Philadelphia, Pennsylvania
"And one slight hair the mighty bulk commands.''
John Gay
H I R s u T I s M is not strictly a primary gynecologic problem. The gynecologist's interest in hirsutism, however, stems from the anxiety of women in regard to excessive hair growth and the possibility that hirsutism may be a signpost of virilization. To cope successfully with questions raised by hirsute patients and to afford intelligent differential diagnosis, the gynecologist must be informed concerning the physiology of hair as well as of its abnormal growth; he must be familiar not only with the embryonal relations of adrenal, ovary, and testis but also with the recently enunciated, similar metabolic pathways of progesterone, testosterone, and estrogen in these organs; finally, he must be aware of the available cosmetic measures to remove
fetal life, hair making its first appearance on the eyebrows, upper lip, and chin. By the fifth month, the human fetus is covered with fine, vellus hair (lanugo). By the time of birth, the hair of the scalp and eyebrow is well defined, becoming coarser and thicker during childhood. 19 Montagu"" has postulated that such selectively thickened hair is a developmental adaptation to protect frictional sites from chafing and exposed areas lacking subepithelial padding from injury. The main facets of the physiology of hair relate chiefly to endocrine and genetic factors, distorted in the mind of both patient and physician by geographically influenced customs and beliefs. Moreover, the character and distribution of hair are physiologic
excessive hair.
features that affect the differential diagnosis
of hirsutism. Endocrine and genetic factors. The coarse hair appearing during puberty on the pubes and in the axillae of girls represents a response to androgen secreted by the adrenal cortex, possibly also by the hilus cells of the ovary. The differential speed of growth of the ambosexual pubic and axillary hair during adolescence is attributable to local differences in the threshold of response. Moreover, the relative excess of facial and limb hair of some girls may be a familial (genetic I affair, independent of sex. Adolescent males have more hair than females, not only because of genetically directed threshold differences but also because of their additional supply of androgen from the testis. During this time, the hirsutism characteristics of the
Physiology of hair
Hair derives from the same primary epithelial germ layer that gives rise to sebaceous and apocrine glands, accounting for the presence of both hair and sweat glands in such specialized areas as the axilla, pubis, mammary areola, and ear canal. Both systems, pilar and sebaceous, begin their embryologic growth during the third month of From the Department of Gynecology and Obstetrics, Graduate School of Medicine, University of Pennsylvania. and the Pennsylvania Hospital. Guest Address, presented at the Twenty-fifth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Feb. 3-6, 1963.
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male are evident in the upper portion of the pubic hair, beard, ear canal, and over the sternum. Except for the lower portion of the vulva, estrogen does not stimulate hair growth. The presence of excessive estrogen for prolonged periods may be responsible for thinning of body hair in males, particularly in the axillary and pubic regions; scalp hair is not affected by such estrogen. Male pattern alopecia is genetic in origin but dependent upon the presence of androgen. Such alopecia appears in women following prolonged exposure to excessive androgen, but only when they possess the unexpressed hereditable factor. 18 • 19 Customs and beliefs. Contrary to popular belief, shaving or cutting the hair does not cause its more rapid growth. Such activities, removing only the hair shaft above the skin surface, have no effect upon the matrix, the mitotic center under the skin wherefrom hair grows. Women of Latin (Mediterranean) origin, accustomed to more body hair, have less emotional disturbance concerning hair growth than do Nordic women. This is illustrated by the quaint belief that mustache hair, so characteristic of Latin-type women, is a sign of an affectionate, loving nature. Such women, relatively undisturbed by body hair, do not routinely shave their axillae; the preservation of axillary hair may, in certain cultures, have sexual attractiveness. 35 American women, on the other hand, are far more sensitive to facial as well as to body hair, and their axillae are kept hair-free by repetitive shaving. Character and sites of hirsutism. Growth of facial and body hair in women assumes importance medically because of the possibility that it is part of a virilizing syndrome which, if identified, may be reversed by proper therapy, a possibility made more likely when the hair growth is sudden. The hirsutic change may be increased quantity as well as altered distribution; when associated with amenorrhea and infertility, such superfluous hair impels close attention by the gynecologist. The diagnostic problem
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arises, however, because hirsutism in women is not always evidence of an endocrine disorder. There is also no clear division between hair growth that is excessive and that which is normal, particularly if the site is considered. 13 • 18 • 46 The forearm and leg, where hair is often nonspecific, are not good places to estimate abnormalities of hair growth. Hair of the upper lip, chin, sternal area, ear canal, over the digits of the hand, inner aspect of upper thigh, and sacral area is more likely to be of hormonal origin. In these areas, hair growth in women is "sexually determined and related to blood hormone levels or to sensitivity of hair follicles to circulating hormone." 13 The question is further complicated by a genetic factor as well as that of skin coloring. Women of hirsute families may develop some hair, appearing first during puberty, on uncommon sites. Moreover, light-colored facial hair which would pass unnoticed in a blonde is different from the conspicuously superfluous dark hair of a brunette, making hirsutism more of a cosmetic problem in the dark-complexioned woman. The differential diagnosis of abnormal hair growth involves four categories-physiologic, therapeutic (iatrogenic), idiopathic, and that related to virilization. Because of the latter, the main diagnostic effort is directed toward differentiating an adrenocortical from an ovarian lesion.
Physiologic hirsutism Excessive, though not grossly abnormal, growth of hair may be evident in women during puberty, pregnancy, and the menopause. Puberty. The adolescent girl who has a familial tendency toward hairiness, responding readily to both adrenal and ovarian androgen, is apt to grow hair in sites other than the pubic and axillary areas. Such physiologic hirsutism appears on the arms, legs, upper lip, and lower abdomen. Facial acne is a frequent accompaniment, giving evidence of the relation between the pilar system and apocrine glands. The ultimate
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quantity of hair such a girl develops, depending largely on heredity (though the mechanism remains unknown), varies widely. In general, when there is no associated menstrual disorder, familial hirsutism of the adolescent girl may be managed medically by repetitive reassurance and cosmetic advice. Pregnancy. There is often increased growth of scalp and body hair during pregnancy because there are fewer hairs in a resting phase, representing responsiveness to androgenic substances coming perhaps from the placenta or the hilus cells of the ovary stimulated by chorionic gonadotropin. 51 Moreover, excessive hair growth existing prior to pregnancy tends to be accelerated. 52 The pregnant woman, scarcely noticing her thicker scalp hair, rarely fails to observe the loss of the new hair during the late puerperium, the delayed result of hair follicles having returned to their periodic rest phase at the termination of pregnancy. However, by the time the patient becomes aware of patchy loss of scalp hair late postpartally, it is not really a medical problem. The falling-out of hair indicates that such shafts were merely held in the skin during an imperceptible period of no growth. When the resting phase is over new hairs push out the dead shafts. 28 The woman should be reassured for the alopecia is not permanent, new hairs being already in place. The mildly excessive, physiologic hair growth of pregnancy must not be confused with the intense hirsutism characteristic of masculinizing tumors that can complicate pregnancy. 15 ' 36 Menopause. During the menopausal years there is apt to be slight hirsutism of the upper lip and chin, particularly in brunettes. It is accountable to the relative increase in adrepocortical hormones that occurs in some women as a result of the pituitary gonadotropic overactivity which follows cessation of ovarian hormone production. This hypothesis finds support in the responsiveness of the adrenal cortex to chorionic gonadotropin administered to castrated women. 11 Fortunately, such menopausal hirsutism requires
no more than reassurance to the patient that it will grow no worse and, occasionally, the use of electrolysis for isolated hairs. Therapeutic (iatrogenic! hirsutism
Excessive hair growth is an unwanted side effect of the administration of androgen to women that limits clinical usefulness of the hormone. This cosmetic and psychologic hazard must be evaluated thoughtfully by the gynecologist whenever he prescribes androgen. Under circumstances requiring intensive androgenic therapy, metastatic mammary carcinoma and crippling osteoporosis, the woman must bear the jeopardy. The density of such therapeutically induced hirsutism varies with the patient's susceptibility to and the dosage of androgen. Susceptiveness of women to androgen is highly individual. Except for the acknowledged sensitiveness of brunettes and of women with a seborrheic type of skin, 3 • 1 the proneness to hirsutism is unpredictable. For this reason the gynecologist should approach the initial prescription of androgen for such entities as endometriosis, cyclic mammary pain, and premenopausal dysfunctional bleeding warily. It is not wise to give more than 100 mg. of testosterone propionate intramuscularly or 150 mg. of methyltestosterone orally during one month. Unfortunately, even these limited doses are not reliably safe. Women being treated with androgen must have careful, repeated observation. If the administration of androgen is continued after hirsutism has developed, acne, enlargement of the clitoris, and alteration of the vocal cords are likely to appear. Male-pattern alopecia does not occur readily, requiring not only administration of androgenic hormone during a prolonged period but also the presence of a genetic factor, the hereditable predisposition for such alopecia, as well.~· 7 • w Idiopathic hirsutism
The most baffling, certainly the most clinically frustrating, variety of excessive facial and body hair growth is that occurring in an otherwise normal woman. Some degree
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of such hirsutism, appearing first during adolescence and remaining unassociated with menstrual dysfunction, is estimated to occur in about one third of the adult women. 55 Most of this is borne with quiet resignation, abetted by the judicious help of beauty aids. A minority of this hirsute group do, however, seek medical help for the hairiness alone; some of them develop obesity, possibly from compulsive eating as a psychological reaction to their esthetic affliction. 5 These few require close differential diagnosis, despite their normal menses, since hirsutism alone may, albeit uncommonly, be the signpost of an adrenal cortical tumor. 26 The etiology of idiopathic hirsutism has been attributed to the presence of hair follicles congenitally hypersensitive to normal levds of androgen. Indeed, this seems to be supported in many such women by a familial tendency to hairiness. Consistent efforts have been made to demonstrate excessive androgenic production'· 17 • 23 as well as abnormal metabolism of androgens 39 in such women. During the past twenty years, the evidence has been controversial regarding the contention that the metabolites of adrenocortical-type androgens, dehydroepiandrosterone and etiocholanolone, are excreted in excess by women with idiopathic hirsutism. 7 More recently, the theme of testosterone excess has been introduced as the basic cause of most androgenicity in women, including idiopathic hirsutism. 14 • 47 Plate 40 first proposed that the ovaries are capable of producing testosterone, just as the testis and adrenal cortex are. The normal biosynthetic pathway for the formation of estrogen in the ovary includes the manufacture of androgenic precursors of testosterone 42 (Fig. 1). In fact, it is probable that the metabolic steps are similar in all organs producing steroidal hormones, including the adrenal, testis, ovary, and placenta. 24 • 25 • 34 • 43 Yet to be resolved, however, are the problems related to the comparative effects of the presence of endogenous and exogenous hormones on the multiple factors that affect biosynthetic pathways, 30 including the rate of secretion in the several nontesticular sites of
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production 32 or of conversion 27 to testosterone. Nonetheless, if the biosynthetic pathway in the ovary is deranged because of the lack of one or more enzymes, estrogen is not well produced but its androgenic precursors and possibly testosterone are. 2 • 30 For such cogent reasons, the gynecologist may not now indulge in a diagnosis of idiopathic hirsutism even in the absence of menstrual dysfunction unless he has clearly eliminated the presence of the specific ovarian and adrenal disorders notably associated with excessive hair growth.
Ovarian hirsutism Two ovarian disorders cause excessive hair growth and menstrual dysfunction, androgen-producing tumors and the polycystic ovary syndrome. Masculinizing tumors. Certain ovarian tumors cause amenorrhea and marked hirsutism in association with only moderate elevation of urinary 17 -ketosteroids. 21 • 38 The recent finding of testosterone in arrhenoblastomas1• 16 and the demonstration that slices of such a tumor/ 5 as well as those from a luteoma/ 4 could produce testosterone from added progesterone have led to the viewpoint previously mentioned that testosterone per se is the significant androgen in
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hirsutism. If this is the case, excessive levels of 17 -ketosteroid excretion are not required to explain the hirsutism. Inasmuch as testosterone is more virilizing than any other known androgen, only minute quantities of it are needed to cause the dense hirsutism typical of masculinizing tumors. Such testosterone, identified in blood by sensitive tests, 14 would appear in the urine only in the form of its metabolic products~etiocholanolone, dehydroepiandrosterone, and androstene· dione. If this pathogenic biosynthesis takes place in the two tumors shown to contain testosterone, the arrhenoblastoma and the luteoma (lipoid-cell, adrenallike tumor), the same mechanism may evoke the hirsutism and amenorrhea of ovarian hilar cell tumors. This explains how a tumor of hilus cells, too small to be palpated and undiagnosed for 10 years because of relatively normal urinary levels of 17 -ketosteroids, could cause hirsutism and male-type alopeciaY Polycystic ovary syndrome. No other condition of the ovary related to menstrual dysfunction, hirsutism, and sterility has been accorded the singular attention given to the polycystic state. Although recognized previously, 8 the polycystic syndrome has become classic since its clinical description by Stein and Leventhal 50 in 1935. This diagnosis must be considered in all moderately hirsute, infertile women who give a history of menstrual dysfunction extending back to puberty, even if the ovaries are not grossly enlarged. 29 • 41 • 48 The recent demonstration that the polycystic ovary is capable of producing several kinds of androgen, including testosterone/• 24 • " 0 • " links the hirsutism of this condition to that of both the idiopathic variety and ovarian tumors. Another hypothesis33 suggests that the ovary secretes not testosterone but only its weakly androgenic precursors, and that these are converted in the liver to testosterone. 27 Further confusion, however, arises from evidence supporting an alternative concept that polycystic ovaries, •. 39 as well as the hyperthecosis often associated with it,' 0 • 12 result from adrenocortical hyperfunction. The mecha-
nism which alters ovarian steroidal biosynthesis, whether of pituitary""· '':l or genetic:" causation, and the true relation of the adrenal to this syndrome await solution. Equally unresolved is the explanation for the clinical effectiveness of wedge resection of polycystic ovaries. The hirsutism of the polycystic ovary syndrome, in contradistinction to that of mas· culinizing tumors, is moderate. It is usually seen as a fuzzy down involving the chin and upper lip, in association with some periareolar or sternal hair and a masculine pubic escutcheon (Fig. 2). Occasionally, particularly in brunettes, there is likely to be ex· cessive hair of the forearm and legs but, inasmuch as these are sites of indifferent (nonendocrine) hair growth, such hirsutism alone warrants no diagnostic emphasis. In the early stage of the polycystic ovary syndrome it is not easy to draw the line between it and an adrenal disorder. 2 "· 41 To distinguish them, the use of the culdoscope, intravenous urography, perirenal air injection studies. and differential stimulation and suppression of the adrenal cortex by successive test administration of ACTH and cortisone are required. The stimulatory test is more accurate in determining the likelihood of an adrenal cortical disorder. Adrenal hirsutism
When the origin of hirsutism is in the adrenal cortex, the differential diagnosis concerns identification of the type of adrenal overactivity. Moreover, the degree of such hyperactivity varies widely, hinging upon the pathologic process (tumor or hyperplasia) as well as upon the adrenocortical zones involved. The distinction between hyperplasia and neoplasm is not readily apparent but requires intravenous urography, perirenal air study, and special diagnostic tests (Table l). The adrenogenital syndrome and the Cushing syndrome are the two main varieties of adrenocortical hyperfunction. Adrenogenital syndrome. The manifestations of the adrenogenital syndrome vary with the age of the patient at the onset of
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Fig. 2. Periareolar and sternal hair, typical of the hirsutism· of the polycystic ovary syndrome.
the disorder. If it is congenital, beginning during intrauterine life, there is usually some maldevelopment of the external genitals ( adrenal-nongonadal female pseudohermaphroditism). Such introital deformities may be identified in a girl at birth; in fact, th ey may give rise to confusion regarding the infant's proper sex. By the time she attains puberty, her development has taken a decidedly male turn, including masculine habitus, hirsutism, and absence of menstruation. Because of an inborn enzymatic deficiency there is failure of the adrenal to synthesize cortisone, resulting in excessive excretion of both 17-ketosteroids and pregnanetriol ; the latter is pathognomonic of this condition. 6 • :n, 49 The self-perpetuating cycle of excessive ACTH production by the pituitary, the result of the lack of cortisone, and the continued elaboration of immoderate quantities of 17 -ketosteroids and pregnanetriol not only evoke masculinization but also prevent proper ovarian function . The administration of cortisone to inhibit ACTH secretion interrupts the abnormal adrenalpituitary cycle and leads to reduction of the urinary output of both 17 -ketosteroids and pregnanetriol, ultimately permitting feminization to take place."" When the adrenal overactivity is not congenital, its onset being in childhood or dur-
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ing adult life, the differential diagnosis between tumor and hyperplasia is imperative. Most instances of this condition in children are of neoplastic origin, usually malignant. 4 ' The clinical manifestations of late-appearing adrenocortical hyperactivity in the adult woman ranges from hirsutism alone 26 to defeminization and ultimate virilism. 31 Typically, the illness is initiated by hirsutism, followed shortly by oligomenorrhea that eventuates in amenorrhea. The majority of such women have bilateral cortical adrenal hyperplasia. The neutral urinary 17-ketosteroids are elevated but the 17-hydroxysteroids remain normal. 22 • 47 The pathogenesis of this disorder, though late in appearing, is probably similar to that of the congenital variety.9 • 3 1 • 4 1 Treatment with cortisone is effective, restoring menses and fertility.22 • " '; Cushing's syndrome. The adult woman who develops hirsutism and amenorrhea as a result of adrenal hyperactivity may have panhypercorticalism, in which case both symptoms will be overshadowed by other associated manifestations. The bizarre truncal obesity, almost ludicrously thin extremities, purplish or pink striae, excessive fatigue, abnormal carbohydrate metabolism, hypertension, and osteoporosis are the signposts that impel execution of differential laboratory studies to establish the precise adrenal cause- hyperplasia, adenoma, or carcinoma. An occasional diagnostic dilemma may arise when some of the features of Cushing's syndrome are caused by a masculinizing lipoid cell tumor ( adrenallike) of the ovary. 3G . •~B. 4' Management of excessive hair
Aside from the medical importance of hirsutism, entailing accurate differential diagnosis to identify its cause, the patient's concern is increased because of the unsightliness of superfluous hair. Moreover, even when the diagnosis is established and the patient is subjected to definitive treatment, rapid resolution of the hirsuties should not be anticipated. The woman whose ovulatory menstrual pattern is restored following ovar-
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Table I. Differential diagnosis of hirsutism of adrenal origin Stimulation test
Suppression test
Baseline plasma level of Baseline 24 hour urine 1 7 -hydroxycorticoassay for 17-ketosteroids steroids and 1 7hydroxycorticosteroids Dexamethasone* 0.5 ACTH ( 25 JL/500 mi. physiologic saline) mg. every 6 hours intravenously from for 3 days, collecting 8 A.M. to noon, draw24 hour urine on ing plasma sample for third day (while still cf. 17-hydroxycorticotaking dexamethasone) steroid level immediately thereafter No change
Tumor No change
Hyperplasia Doubling or trebling of Fifty per cent decrease plasma 17-hydroxyin both 17-ketocorticosteroid level steroids and 17hydroxycorticosteroids *(Decadron), !'vferck Sharpe & Dohmc.
ian wedge-resection, excision of an adrenal tumor, or cortisone treatment of adrenocortical hyperplasia, will continue to be annoyed by excessive hair grovvth for a vary . . ingly long time. There is no obvious explanation for such persistence of hirsutism; it appears that the pilary system, once influenced, continues to respond long after removal of the abnormal stimulus. For this reason, the subject of hair removal must perforce be discussed with the patient. Because women receive cosmetic advice from several sources, the gynecologist should be prepared either to condemn or to condone the hair-removal plans of his hirsute patients who usually learn to cope with excessive body hair but regard even occasional facial hairs as inordinately troublesome. Body hair. Most women are able to ignore hirsutism of the forearms and of the lower abdomen but must regularly remove excessive hair over the sternum and on the legs. Careful use of scissors is sufficient to control the hair of the chest and shaving is most useful for that of the legs. An electric r~'7Ar
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risk of skin irritation. Once adept in the use
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of an electric razor, the patient may be permitted to employ it for the removal of facial hair. Such shaving wiii not, contrary to popular notion, evoke excessive hair growth. It may be carried out repetitively with safety. Facial hair. In addition to an electric razor, women avail themselves of other modalities to remove unsightly facial hair. These include the use of depilatories, both systemic and local, as well as of tweezers, abrasive massage, bleaches, and electricity. Depilatories. Certain orally ingested chemicals, such as thallium acetate, having a specific toxic action on hair follicles making them useful for epilation of the scalp. are occasionally recommended in creams for facial use. Such systemic agents must not he used because of their dangerous neurotoxicity. Locally applied depilatories, such as those containing barium or strontium sulfide, are effective but unpleasant because of vile odor and the likelihood of skin irritation. Wax depilation is effective and relatively safe, if the patient can bear to do it. Such depilatories, containing beeswax, rosin, and mineral oil, are solid when cool but in a liquid state when warm. The wax mixture is applied as a warm liquid to the washed and dried skin. The area is then cooled, permitting the wax to congeaL It is removed by a pulling motion, extracting the hair in much the same fashion as adhesive tape does when it is pulled away from the skin. Tweezing, massage, and bleaching. The use of tweezers may be justified for occasional hairs on the chin and upper portion of the neck but it should never be condoned around the lips and nares. The same may be said for abrasive massage with pumice, a porous volcanic glass of light weight, which may be used to remove hairs mechanically by friction following the application of a bland emollient to the skin. Bleaches, serving only to make hair less visible, are useful if the skin is not irritated by them. The combination of weak solutions of both hydrogen peroxide and a1nmonia makes an effective bleach. 3
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Electricity. Galvanic current destroy11 individual hairs permanently by electrolysis and, if properly applied, is safe, It is a slow method, requiring patience for multiple sessions. Electrocoagulation employing diathermy high-frequency current is much faster inasmuch as more hairs may be removed at each sitting. Both methods require caution, aseptic technique, and a trained, skilled operator. Ionizing radiation, such as the x-rays used on occasion for epilation of the scalp infected by ringworm, is dangerous and has no place in the removal of excessive hair in women. Summary and conclusions
Excessive hair in women, disturbing to them because of its unsightliness, becomes a gynecologic problem since it may be a sign of virilization. The physiology of hair growth,
REFERENCES
1. Anliker, R., Rohr, 0., and Ruzicka, L.: Ann. chem. 603: 109, 1957. 2. Axelrod, L. R., and Goldzieher, J. W.: J. Clin. Endocrinol. 22: 431, 1962. 3. Behrman, H. T.: J. A.M. A. 172: 1924, 1960. 4. Benedict, P. H., Cohen, R. B., Cope, 0., and Scully, R. E.: Fertil. & Steril. 13: 380, 1962. 5. Bissell, G. W.: Ann. New York Acad. Sc. 53: 742, 1951. 6. Bongiovanni, A. M., and Eberlein, W. R.: Pediatrics 21: 661, 1958. 7. Brooksbank, B. W. L.: Physiol. Rev. 41: 624, 1961. 8. Broster, L. R.: Lancet 1: 830, 1934. 9. Bush, I. E., and Mahesh, V. B.: J. Endocrinol. 18: 1, 1959. I 0. Case Record, Massachusetts General Hospital: New England J. Med. 246: 667, 1952. 11. Decio, R.: Acta endocrinol. 19: 185, 1955. 12. Feher, G., Gyorgy, G., Less, E., and Laszlo, J.: Acta endocrinol. 28: 219, 1958. 13. Ferriman, D., and Gallwey, J. D.: J. Clin. Endocrinol. 21: 1440, 1961. 14. Finkelstein, M., Forchielli, E., and Dorfman, R. 1.: J. Clin. Endocrinol. 21: 98, 1961. 15. Friedman, I. S., Mackles, A., and Daichman. 1.: J. Clin. Endocrinol. 15: 1281, 1955. 16. Gallagher, T. F. et al.: J. Clin. Endocrinol. 22: 970, 1962. 17. Gardner, L. I.: J. Clin. Endocrinol. 13: 1054, 1953. 18. Garn, S. M.: Ann. New York Acad. Sc. 53: 498, 1951.
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as well as some of the universal myths associated with it, should be familiar to the gynecologist. The differential diagnosis of hirsutism includes physiologic and iatrogenic origins. Though idiopathic hirsutism occurs frequently, . such a diagnosis must not be accepted until ovarian and adrenal causes of excessive hair growth have been sought and not found. Recent evidence has shown that the biosynthetic pathways of steroid production in adrenal, ovary, testis, and placenta are similar, tending to support a unified hypothesis of the etiology of hirsutism-one related to enzymatic deficiencies that involve estrogenandrogen relations. Women afflicted by hirsutism) whatever its origin, should be advised concerning the most cosmetically effective, safest methods of hair removal.
19. Hurley, H. J.: Pennsylvania M. J. 64: 371, 1961. 20. Ingersoll, F. M., and McArthur, J. W.: AM. J. 0BST. & GYNEC. 77: 795, 1959. 21. Israel, S. L., and Mutch, J. C.: Surg. Gynec. & Obst. 105: 166, 1957. 22. Jones, H. W., Jr., and Jones, G. E. S.: AM. J. 0BST. & GYNEC. 68: 1330, 1954. 23. Kappas, A., Pearson, 0. H., West, C. E., and Gallagher, T. F.: J. Clin. Endocrinol. 16: 517, 1956. 24. Kase, N., Forchielli, E., and Dorfman, R. I.: Acta endocrinol. 37: 19, 1961. 25. Kase, N., and Kowal, J.: J. Clin. Endocrinol. 22: 925, 1962. 26. Kinsell, L. W., and Lisser, H.: J. Clin. Endocrinol. 12: 50, 1952. 27. Klempien, E. J., Voigt, K. D., and Tamm, J.: Acta endocrinol. 36: 498, 1961. 28. Kligman, A. M.: A. M. A. Arch. Dermat. 83: 175, 1961. 29. Lanthier, A., Lauze, S., and Grignon, C. E.: Am. J. M. Sc. 239: 585, 1960. 30. Lanthier, A., and Sandor, T.: Acta endocrinol. 39: 145, 1962. 31. Lipsett, M. B., and Riter, B. D.: Acta endocrinol. 38: 481, 1961. 32. MacDonald, P. C., Vande Wiele, R. L., and Lieberman, S.: J. Clin. Endoc:rinol. 22: 1222, 1229, 1962. 33. Mahesh, V. B., and Greenblatt, R. B.: J. Clin. Endocrinol. 22: 441, 1962. 34. Mahesh, V. B., Greenblatt, R. B., Aydar, C. K., and Roy, S.: Fertil. & Steril. 13: 513, 1962.
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35. Montagu, A.: J. A. M. A. 182: 281, 1962. 36. Morris, J. MeL., and Scully, R. E.: Endocrine Pathology of the Ovary, St. Louis, 1958, The C. V. Mosby Company. 37. Netter, A. P.: Proc. Roy. Soc. Med. 54: 1006, 1961. 38. Pedowitz, P., and Pomerance, W.: Obst. & Gynec. 19: 183, 1962. 39. Perloff, H. W., Channick, B. J., Suplick, B., and Carrington, E. R.: J. A. M. A. 167: 2041, 1958. 40. Plate, W. P.: Acta endocrinol. 8: 17, 1951. 41. Prunty, T. F. G., Brook, R. V., and Mattingly, D.: Brit. M. J. 2: 1554, 1958. 42. Ryan, K. J.: In Popjak, G., editor: Proceedings of Fifth International Congress of Biochemistry, Biosynthesis of Lipids, London, 1962, Pergamon Press, vol. 7. 43. Ryan, K. ]., and Smith, 0. W.: J. Bioi. Chern. 236: 710, 1961. 44. Sandberg, A. A., Slaunwhite, W. R., Jr., Jackson, J. E., and Frawley, T. F.: J. Clin. Endocrinol. 22: 929, 1962. 45. Savard, K., et a!.: J. Clin. Endocrinol. 21: 165, 1961.
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46. Shah, P. N.: AM. J. 0BST. & GY;-.;Ec. 73: 1255, 1957. 47. Soffer, L. J., Dorfman, R. 1., and Gabrilove. J. L.: The Human Adrenal Gland. Philadelphia, 1961, Lea & Febiger. 48. Southam, A. L.: Ann. New York Acad. Sr. 75: 840, 1959. 49. Staub, M. C., Gaitan, E., and Dingman, J. F.: ]. Clin. Endocrinol. 22: 87, 1962. 50. Stein, I. F., and Leventhal, M. L.: AM. J. 0BsT. & GYNEC. 29: 181, 1935. 51. Sternberg, W. H., Segaloff, A., and Gaskill. C. J.: J. Clin. Endocrinol. 13: 139, 1953. 52. Stoddard, F. J.: AM. J. OBsT. & GYNEC. 49: 417, 1945. 53. Taymor, M. L., and Barnard, R.: Fertil. & Steril. 13: 501, 1962. 54. Warren, J. C., and Salhanick, H. A.: J. Clin. Endocrinol. 21: 1218, 1961. 55. Weed, ]. C.: AM. J. 0BsT. & GYNEC. 69: 1348, 1955. 56. Wilkins, L.: J. Pediat. 41: 860, 1952. 807 Spruce St. Philadelphia 7, Pennsylvania
"And one slight hair the mighty bulk commands.''
John Gay
H I R s u T I s M is not strictly a primary gynecologic problem. The gynecologist's interest in hirsutism, however, stems from the anxiety of women in regard to excessive hair growth and the possibility that hirsutism may be a signpost of virilization. To cope successfully with questions raised by hirsute patients and to afford intelligent differential diagnosis, the gynecologist must be informed concerning the physiology of hair as well as of its abnormal growth; he must be familiar not only with the embryonal relations of adrenal, ovary, and testis but also with the recently enunciated, similar metabolic pathways of progesterone, testosterone, and estrogen in these organs; finally, he must be aware of the available cosmetic measures to remove
fetal life, hair making its first appearance on the eyebrows, upper lip, and chin. By the fifth month, the human fetus is covered with fine, vellus hair (lanugo). By the time of birth, the hair of the scalp and eyebrow is well defined, becoming coarser and thicker during childhood. 19 Montagu"" has postulated that such selectively thickened hair is a developmental adaptation to protect frictional sites from chafing and exposed areas lacking subepithelial padding from injury. The main facets of the physiology of hair relate chiefly to endocrine and genetic factors, distorted in the mind of both patient and physician by geographically influenced customs and beliefs. Moreover, the character and distribution of hair are physiologic
excessive hair.
features that affect the differential diagnosis
of hirsutism. Endocrine and genetic factors. The coarse hair appearing during puberty on the pubes and in the axillae of girls represents a response to androgen secreted by the adrenal cortex, possibly also by the hilus cells of the ovary. The differential speed of growth of the ambosexual pubic and axillary hair during adolescence is attributable to local differences in the threshold of response. Moreover, the relative excess of facial and limb hair of some girls may be a familial (genetic I affair, independent of sex. Adolescent males have more hair than females, not only because of genetically directed threshold differences but also because of their additional supply of androgen from the testis. During this time, the hirsutism characteristics of the
Physiology of hair
Hair derives from the same primary epithelial germ layer that gives rise to sebaceous and apocrine glands, accounting for the presence of both hair and sweat glands in such specialized areas as the axilla, pubis, mammary areola, and ear canal. Both systems, pilar and sebaceous, begin their embryologic growth during the third month of From the Department of Gynecology and Obstetrics, Graduate School of Medicine, University of Pennsylvania. and the Pennsylvania Hospital. Guest Address, presented at the Twenty-fifth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Feb. 3-6, 1963.
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male are evident in the upper portion of the pubic hair, beard, ear canal, and over the sternum. Except for the lower portion of the vulva, estrogen does not stimulate hair growth. The presence of excessive estrogen for prolonged periods may be responsible for thinning of body hair in males, particularly in the axillary and pubic regions; scalp hair is not affected by such estrogen. Male pattern alopecia is genetic in origin but dependent upon the presence of androgen. Such alopecia appears in women following prolonged exposure to excessive androgen, but only when they possess the unexpressed hereditable factor. 18 • 19 Customs and beliefs. Contrary to popular belief, shaving or cutting the hair does not cause its more rapid growth. Such activities, removing only the hair shaft above the skin surface, have no effect upon the matrix, the mitotic center under the skin wherefrom hair grows. Women of Latin (Mediterranean) origin, accustomed to more body hair, have less emotional disturbance concerning hair growth than do Nordic women. This is illustrated by the quaint belief that mustache hair, so characteristic of Latin-type women, is a sign of an affectionate, loving nature. Such women, relatively undisturbed by body hair, do not routinely shave their axillae; the preservation of axillary hair may, in certain cultures, have sexual attractiveness. 35 American women, on the other hand, are far more sensitive to facial as well as to body hair, and their axillae are kept hair-free by repetitive shaving. Character and sites of hirsutism. Growth of facial and body hair in women assumes importance medically because of the possibility that it is part of a virilizing syndrome which, if identified, may be reversed by proper therapy, a possibility made more likely when the hair growth is sudden. The hirsutic change may be increased quantity as well as altered distribution; when associated with amenorrhea and infertility, such superfluous hair impels close attention by the gynecologist. The diagnostic problem
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arises, however, because hirsutism in women is not always evidence of an endocrine disorder. There is also no clear division between hair growth that is excessive and that which is normal, particularly if the site is considered. 13 • 18 • 46 The forearm and leg, where hair is often nonspecific, are not good places to estimate abnormalities of hair growth. Hair of the upper lip, chin, sternal area, ear canal, over the digits of the hand, inner aspect of upper thigh, and sacral area is more likely to be of hormonal origin. In these areas, hair growth in women is "sexually determined and related to blood hormone levels or to sensitivity of hair follicles to circulating hormone." 13 The question is further complicated by a genetic factor as well as that of skin coloring. Women of hirsute families may develop some hair, appearing first during puberty, on uncommon sites. Moreover, light-colored facial hair which would pass unnoticed in a blonde is different from the conspicuously superfluous dark hair of a brunette, making hirsutism more of a cosmetic problem in the dark-complexioned woman. The differential diagnosis of abnormal hair growth involves four categories-physiologic, therapeutic (iatrogenic), idiopathic, and that related to virilization. Because of the latter, the main diagnostic effort is directed toward differentiating an adrenocortical from an ovarian lesion.
Physiologic hirsutism Excessive, though not grossly abnormal, growth of hair may be evident in women during puberty, pregnancy, and the menopause. Puberty. The adolescent girl who has a familial tendency toward hairiness, responding readily to both adrenal and ovarian androgen, is apt to grow hair in sites other than the pubic and axillary areas. Such physiologic hirsutism appears on the arms, legs, upper lip, and lower abdomen. Facial acne is a frequent accompaniment, giving evidence of the relation between the pilar system and apocrine glands. The ultimate
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quantity of hair such a girl develops, depending largely on heredity (though the mechanism remains unknown), varies widely. In general, when there is no associated menstrual disorder, familial hirsutism of the adolescent girl may be managed medically by repetitive reassurance and cosmetic advice. Pregnancy. There is often increased growth of scalp and body hair during pregnancy because there are fewer hairs in a resting phase, representing responsiveness to androgenic substances coming perhaps from the placenta or the hilus cells of the ovary stimulated by chorionic gonadotropin. 51 Moreover, excessive hair growth existing prior to pregnancy tends to be accelerated. 52 The pregnant woman, scarcely noticing her thicker scalp hair, rarely fails to observe the loss of the new hair during the late puerperium, the delayed result of hair follicles having returned to their periodic rest phase at the termination of pregnancy. However, by the time the patient becomes aware of patchy loss of scalp hair late postpartally, it is not really a medical problem. The falling-out of hair indicates that such shafts were merely held in the skin during an imperceptible period of no growth. When the resting phase is over new hairs push out the dead shafts. 28 The woman should be reassured for the alopecia is not permanent, new hairs being already in place. The mildly excessive, physiologic hair growth of pregnancy must not be confused with the intense hirsutism characteristic of masculinizing tumors that can complicate pregnancy. 15 ' 36 Menopause. During the menopausal years there is apt to be slight hirsutism of the upper lip and chin, particularly in brunettes. It is accountable to the relative increase in adrepocortical hormones that occurs in some women as a result of the pituitary gonadotropic overactivity which follows cessation of ovarian hormone production. This hypothesis finds support in the responsiveness of the adrenal cortex to chorionic gonadotropin administered to castrated women. 11 Fortunately, such menopausal hirsutism requires
no more than reassurance to the patient that it will grow no worse and, occasionally, the use of electrolysis for isolated hairs. Therapeutic (iatrogenic! hirsutism
Excessive hair growth is an unwanted side effect of the administration of androgen to women that limits clinical usefulness of the hormone. This cosmetic and psychologic hazard must be evaluated thoughtfully by the gynecologist whenever he prescribes androgen. Under circumstances requiring intensive androgenic therapy, metastatic mammary carcinoma and crippling osteoporosis, the woman must bear the jeopardy. The density of such therapeutically induced hirsutism varies with the patient's susceptibility to and the dosage of androgen. Susceptiveness of women to androgen is highly individual. Except for the acknowledged sensitiveness of brunettes and of women with a seborrheic type of skin, 3 • 1 the proneness to hirsutism is unpredictable. For this reason the gynecologist should approach the initial prescription of androgen for such entities as endometriosis, cyclic mammary pain, and premenopausal dysfunctional bleeding warily. It is not wise to give more than 100 mg. of testosterone propionate intramuscularly or 150 mg. of methyltestosterone orally during one month. Unfortunately, even these limited doses are not reliably safe. Women being treated with androgen must have careful, repeated observation. If the administration of androgen is continued after hirsutism has developed, acne, enlargement of the clitoris, and alteration of the vocal cords are likely to appear. Male-pattern alopecia does not occur readily, requiring not only administration of androgenic hormone during a prolonged period but also the presence of a genetic factor, the hereditable predisposition for such alopecia, as well.~· 7 • w Idiopathic hirsutism
The most baffling, certainly the most clinically frustrating, variety of excessive facial and body hair growth is that occurring in an otherwise normal woman. Some degree
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of such hirsutism, appearing first during adolescence and remaining unassociated with menstrual dysfunction, is estimated to occur in about one third of the adult women. 55 Most of this is borne with quiet resignation, abetted by the judicious help of beauty aids. A minority of this hirsute group do, however, seek medical help for the hairiness alone; some of them develop obesity, possibly from compulsive eating as a psychological reaction to their esthetic affliction. 5 These few require close differential diagnosis, despite their normal menses, since hirsutism alone may, albeit uncommonly, be the signpost of an adrenal cortical tumor. 26 The etiology of idiopathic hirsutism has been attributed to the presence of hair follicles congenitally hypersensitive to normal levds of androgen. Indeed, this seems to be supported in many such women by a familial tendency to hairiness. Consistent efforts have been made to demonstrate excessive androgenic production'· 17 • 23 as well as abnormal metabolism of androgens 39 in such women. During the past twenty years, the evidence has been controversial regarding the contention that the metabolites of adrenocortical-type androgens, dehydroepiandrosterone and etiocholanolone, are excreted in excess by women with idiopathic hirsutism. 7 More recently, the theme of testosterone excess has been introduced as the basic cause of most androgenicity in women, including idiopathic hirsutism. 14 • 47 Plate 40 first proposed that the ovaries are capable of producing testosterone, just as the testis and adrenal cortex are. The normal biosynthetic pathway for the formation of estrogen in the ovary includes the manufacture of androgenic precursors of testosterone 42 (Fig. 1). In fact, it is probable that the metabolic steps are similar in all organs producing steroidal hormones, including the adrenal, testis, ovary, and placenta. 24 • 25 • 34 • 43 Yet to be resolved, however, are the problems related to the comparative effects of the presence of endogenous and exogenous hormones on the multiple factors that affect biosynthetic pathways, 30 including the rate of secretion in the several nontesticular sites of
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production 32 or of conversion 27 to testosterone. Nonetheless, if the biosynthetic pathway in the ovary is deranged because of the lack of one or more enzymes, estrogen is not well produced but its androgenic precursors and possibly testosterone are. 2 • 30 For such cogent reasons, the gynecologist may not now indulge in a diagnosis of idiopathic hirsutism even in the absence of menstrual dysfunction unless he has clearly eliminated the presence of the specific ovarian and adrenal disorders notably associated with excessive hair growth.
Ovarian hirsutism Two ovarian disorders cause excessive hair growth and menstrual dysfunction, androgen-producing tumors and the polycystic ovary syndrome. Masculinizing tumors. Certain ovarian tumors cause amenorrhea and marked hirsutism in association with only moderate elevation of urinary 17 -ketosteroids. 21 • 38 The recent finding of testosterone in arrhenoblastomas1• 16 and the demonstration that slices of such a tumor/ 5 as well as those from a luteoma/ 4 could produce testosterone from added progesterone have led to the viewpoint previously mentioned that testosterone per se is the significant androgen in
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376
October l. 1963 Am . .f. Obst. & Cynt><·.
Israel
hirsutism. If this is the case, excessive levels of 17 -ketosteroid excretion are not required to explain the hirsutism. Inasmuch as testosterone is more virilizing than any other known androgen, only minute quantities of it are needed to cause the dense hirsutism typical of masculinizing tumors. Such testosterone, identified in blood by sensitive tests, 14 would appear in the urine only in the form of its metabolic products~etiocholanolone, dehydroepiandrosterone, and androstene· dione. If this pathogenic biosynthesis takes place in the two tumors shown to contain testosterone, the arrhenoblastoma and the luteoma (lipoid-cell, adrenallike tumor), the same mechanism may evoke the hirsutism and amenorrhea of ovarian hilar cell tumors. This explains how a tumor of hilus cells, too small to be palpated and undiagnosed for 10 years because of relatively normal urinary levels of 17 -ketosteroids, could cause hirsutism and male-type alopeciaY Polycystic ovary syndrome. No other condition of the ovary related to menstrual dysfunction, hirsutism, and sterility has been accorded the singular attention given to the polycystic state. Although recognized previously, 8 the polycystic syndrome has become classic since its clinical description by Stein and Leventhal 50 in 1935. This diagnosis must be considered in all moderately hirsute, infertile women who give a history of menstrual dysfunction extending back to puberty, even if the ovaries are not grossly enlarged. 29 • 41 • 48 The recent demonstration that the polycystic ovary is capable of producing several kinds of androgen, including testosterone/• 24 • " 0 • " links the hirsutism of this condition to that of both the idiopathic variety and ovarian tumors. Another hypothesis33 suggests that the ovary secretes not testosterone but only its weakly androgenic precursors, and that these are converted in the liver to testosterone. 27 Further confusion, however, arises from evidence supporting an alternative concept that polycystic ovaries, •. 39 as well as the hyperthecosis often associated with it,' 0 • 12 result from adrenocortical hyperfunction. The mecha-
nism which alters ovarian steroidal biosynthesis, whether of pituitary""· '':l or genetic:" causation, and the true relation of the adrenal to this syndrome await solution. Equally unresolved is the explanation for the clinical effectiveness of wedge resection of polycystic ovaries. The hirsutism of the polycystic ovary syndrome, in contradistinction to that of mas· culinizing tumors, is moderate. It is usually seen as a fuzzy down involving the chin and upper lip, in association with some periareolar or sternal hair and a masculine pubic escutcheon (Fig. 2). Occasionally, particularly in brunettes, there is likely to be ex· cessive hair of the forearm and legs but, inasmuch as these are sites of indifferent (nonendocrine) hair growth, such hirsutism alone warrants no diagnostic emphasis. In the early stage of the polycystic ovary syndrome it is not easy to draw the line between it and an adrenal disorder. 2 "· 41 To distinguish them, the use of the culdoscope, intravenous urography, perirenal air injection studies. and differential stimulation and suppression of the adrenal cortex by successive test administration of ACTH and cortisone are required. The stimulatory test is more accurate in determining the likelihood of an adrenal cortical disorder. Adrenal hirsutism
When the origin of hirsutism is in the adrenal cortex, the differential diagnosis concerns identification of the type of adrenal overactivity. Moreover, the degree of such hyperactivity varies widely, hinging upon the pathologic process (tumor or hyperplasia) as well as upon the adrenocortical zones involved. The distinction between hyperplasia and neoplasm is not readily apparent but requires intravenous urography, perirenal air study, and special diagnostic tests (Table l). The adrenogenital syndrome and the Cushing syndrome are the two main varieties of adrenocortical hyperfunction. Adrenogenital syndrome. The manifestations of the adrenogenital syndrome vary with the age of the patient at the onset of
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Fig. 2. Periareolar and sternal hair, typical of the hirsutism· of the polycystic ovary syndrome.
the disorder. If it is congenital, beginning during intrauterine life, there is usually some maldevelopment of the external genitals ( adrenal-nongonadal female pseudohermaphroditism). Such introital deformities may be identified in a girl at birth; in fact, th ey may give rise to confusion regarding the infant's proper sex. By the time she attains puberty, her development has taken a decidedly male turn, including masculine habitus, hirsutism, and absence of menstruation. Because of an inborn enzymatic deficiency there is failure of the adrenal to synthesize cortisone, resulting in excessive excretion of both 17-ketosteroids and pregnanetriol ; the latter is pathognomonic of this condition. 6 • :n, 49 The self-perpetuating cycle of excessive ACTH production by the pituitary, the result of the lack of cortisone, and the continued elaboration of immoderate quantities of 17 -ketosteroids and pregnanetriol not only evoke masculinization but also prevent proper ovarian function . The administration of cortisone to inhibit ACTH secretion interrupts the abnormal adrenalpituitary cycle and leads to reduction of the urinary output of both 17 -ketosteroids and pregnanetriol, ultimately permitting feminization to take place."" When the adrenal overactivity is not congenital, its onset being in childhood or dur-
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377
ing adult life, the differential diagnosis between tumor and hyperplasia is imperative. Most instances of this condition in children are of neoplastic origin, usually malignant. 4 ' The clinical manifestations of late-appearing adrenocortical hyperactivity in the adult woman ranges from hirsutism alone 26 to defeminization and ultimate virilism. 31 Typically, the illness is initiated by hirsutism, followed shortly by oligomenorrhea that eventuates in amenorrhea. The majority of such women have bilateral cortical adrenal hyperplasia. The neutral urinary 17-ketosteroids are elevated but the 17-hydroxysteroids remain normal. 22 • 47 The pathogenesis of this disorder, though late in appearing, is probably similar to that of the congenital variety.9 • 3 1 • 4 1 Treatment with cortisone is effective, restoring menses and fertility.22 • " '; Cushing's syndrome. The adult woman who develops hirsutism and amenorrhea as a result of adrenal hyperactivity may have panhypercorticalism, in which case both symptoms will be overshadowed by other associated manifestations. The bizarre truncal obesity, almost ludicrously thin extremities, purplish or pink striae, excessive fatigue, abnormal carbohydrate metabolism, hypertension, and osteoporosis are the signposts that impel execution of differential laboratory studies to establish the precise adrenal cause- hyperplasia, adenoma, or carcinoma. An occasional diagnostic dilemma may arise when some of the features of Cushing's syndrome are caused by a masculinizing lipoid cell tumor ( adrenallike) of the ovary. 3G . •~B. 4' Management of excessive hair
Aside from the medical importance of hirsutism, entailing accurate differential diagnosis to identify its cause, the patient's concern is increased because of the unsightliness of superfluous hair. Moreover, even when the diagnosis is established and the patient is subjected to definitive treatment, rapid resolution of the hirsuties should not be anticipated. The woman whose ovulatory menstrual pattern is restored following ovar-
378
Israel
.\m.
Table I. Differential diagnosis of hirsutism of adrenal origin Stimulation test
Suppression test
Baseline plasma level of Baseline 24 hour urine 1 7 -hydroxycorticoassay for 17-ketosteroids steroids and 1 7hydroxycorticosteroids Dexamethasone* 0.5 ACTH ( 25 JL/500 mi. physiologic saline) mg. every 6 hours intravenously from for 3 days, collecting 8 A.M. to noon, draw24 hour urine on ing plasma sample for third day (while still cf. 17-hydroxycorticotaking dexamethasone) steroid level immediately thereafter No change
Tumor No change
Hyperplasia Doubling or trebling of Fifty per cent decrease plasma 17-hydroxyin both 17-ketocorticosteroid level steroids and 17hydroxycorticosteroids *(Decadron), !'vferck Sharpe & Dohmc.
ian wedge-resection, excision of an adrenal tumor, or cortisone treatment of adrenocortical hyperplasia, will continue to be annoyed by excessive hair grovvth for a vary . . ingly long time. There is no obvious explanation for such persistence of hirsutism; it appears that the pilary system, once influenced, continues to respond long after removal of the abnormal stimulus. For this reason, the subject of hair removal must perforce be discussed with the patient. Because women receive cosmetic advice from several sources, the gynecologist should be prepared either to condemn or to condone the hair-removal plans of his hirsute patients who usually learn to cope with excessive body hair but regard even occasional facial hairs as inordinately troublesome. Body hair. Most women are able to ignore hirsutism of the forearms and of the lower abdomen but must regularly remove excessive hair over the sternum and on the legs. Careful use of scissors is sufficient to control the hair of the chest and shaving is most useful for that of the legs. An electric r~'7Ar
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risk of skin irritation. Once adept in the use
J.
October I, 196:; Obst. & Gynrc.
of an electric razor, the patient may be permitted to employ it for the removal of facial hair. Such shaving wiii not, contrary to popular notion, evoke excessive hair growth. It may be carried out repetitively with safety. Facial hair. In addition to an electric razor, women avail themselves of other modalities to remove unsightly facial hair. These include the use of depilatories, both systemic and local, as well as of tweezers, abrasive massage, bleaches, and electricity. Depilatories. Certain orally ingested chemicals, such as thallium acetate, having a specific toxic action on hair follicles making them useful for epilation of the scalp. are occasionally recommended in creams for facial use. Such systemic agents must not he used because of their dangerous neurotoxicity. Locally applied depilatories, such as those containing barium or strontium sulfide, are effective but unpleasant because of vile odor and the likelihood of skin irritation. Wax depilation is effective and relatively safe, if the patient can bear to do it. Such depilatories, containing beeswax, rosin, and mineral oil, are solid when cool but in a liquid state when warm. The wax mixture is applied as a warm liquid to the washed and dried skin. The area is then cooled, permitting the wax to congeaL It is removed by a pulling motion, extracting the hair in much the same fashion as adhesive tape does when it is pulled away from the skin. Tweezing, massage, and bleaching. The use of tweezers may be justified for occasional hairs on the chin and upper portion of the neck but it should never be condoned around the lips and nares. The same may be said for abrasive massage with pumice, a porous volcanic glass of light weight, which may be used to remove hairs mechanically by friction following the application of a bland emollient to the skin. Bleaches, serving only to make hair less visible, are useful if the skin is not irritated by them. The combination of weak solutions of both hydrogen peroxide and a1nmonia makes an effective bleach. 3
Volume 87 Number 3
Electricity. Galvanic current destroy11 individual hairs permanently by electrolysis and, if properly applied, is safe, It is a slow method, requiring patience for multiple sessions. Electrocoagulation employing diathermy high-frequency current is much faster inasmuch as more hairs may be removed at each sitting. Both methods require caution, aseptic technique, and a trained, skilled operator. Ionizing radiation, such as the x-rays used on occasion for epilation of the scalp infected by ringworm, is dangerous and has no place in the removal of excessive hair in women. Summary and conclusions
Excessive hair in women, disturbing to them because of its unsightliness, becomes a gynecologic problem since it may be a sign of virilization. The physiology of hair growth,
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as well as some of the universal myths associated with it, should be familiar to the gynecologist. The differential diagnosis of hirsutism includes physiologic and iatrogenic origins. Though idiopathic hirsutism occurs frequently, . such a diagnosis must not be accepted until ovarian and adrenal causes of excessive hair growth have been sought and not found. Recent evidence has shown that the biosynthetic pathways of steroid production in adrenal, ovary, testis, and placenta are similar, tending to support a unified hypothesis of the etiology of hirsutism-one related to enzymatic deficiencies that involve estrogenandrogen relations. Women afflicted by hirsutism) whatever its origin, should be advised concerning the most cosmetically effective, safest methods of hair removal.
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35. Montagu, A.: J. A. M. A. 182: 281, 1962. 36. Morris, J. MeL., and Scully, R. E.: Endocrine Pathology of the Ovary, St. Louis, 1958, The C. V. Mosby Company. 37. Netter, A. P.: Proc. Roy. Soc. Med. 54: 1006, 1961. 38. Pedowitz, P., and Pomerance, W.: Obst. & Gynec. 19: 183, 1962. 39. Perloff, H. W., Channick, B. J., Suplick, B., and Carrington, E. R.: J. A. M. A. 167: 2041, 1958. 40. Plate, W. P.: Acta endocrinol. 8: 17, 1951. 41. Prunty, T. F. G., Brook, R. V., and Mattingly, D.: Brit. M. J. 2: 1554, 1958. 42. Ryan, K. J.: In Popjak, G., editor: Proceedings of Fifth International Congress of Biochemistry, Biosynthesis of Lipids, London, 1962, Pergamon Press, vol. 7. 43. Ryan, K. ]., and Smith, 0. W.: J. Bioi. Chern. 236: 710, 1961. 44. Sandberg, A. A., Slaunwhite, W. R., Jr., Jackson, J. E., and Frawley, T. F.: J. Clin. Endocrinol. 22: 929, 1962. 45. Savard, K., et a!.: J. Clin. Endocrinol. 21: 165, 1961.
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