Sexual Hair Growth Research Articles

Endocrinology of Hirsutism: From Androgens to Androgen Excess Disorders.

Unwanted sexual hair growth has a considerable negative impact on a woman's self-esteem and quality of life. Excessive growth of terminal hair in women in a man-like pattern is defined as hirsutism and affects up to 1 in 7 women. Androgens secreted by the ovary and adrenal are the main regulator of physiological and pathological alterations of skin hair. Hirsutism is the result of the interaction between circulating serum androgens and hair follicles. Hirsutism is the most commonly used clinical diagnostic criterion of hyperandrogenism and majority of hirsutism cases are due to androgen excess. Over 80% of women with hirsutism will have polycystic ovary syndrome, about 10% will have idiopathic hirsutism, and the remaining will have rare disorders including non-classical congenital adrenal hyperplasia, hyperandrogenism with insulin resistance and acanthosis nigricans, and androgen-secreting neoplasms. Cushing's syndrome, acromegaly, thyroid dysfunction and hyperprolactinemia might be associated with hirsutism as well as the use of androgens, anabolic steroids and valproate. This paper provides an overview of the principal endocrinological aspects of hirsutism including the role of androgens in excessive hair growth and associated androgen excess disorders. Clinical evaluation and management of hirsutism are also discussed.

Pubertal Development

Pubertal Development

Premature adrenarche: an audit of endocrine profile and management in the outpatient setting

Aims Premature adrenarche (PA) is a common reason for referral to a paediatric clinic. There is little data on the clinical characteristics of these patients from the United Kingdom. Our aim is to audit the clinical presentation and management of PA in the outpatient setting. Subjects and methods The auxology, pubertal status and endocrine profile of all children with a diagnosis of PA in an inner-city hospital from 1/1/2010 to 31/12/2010 were retrospectively audited. Results A total of 37 children were identified, the majority of whom were girls (84%). The mean age at presentation was 7.06 years (±2.26 years). 20/37 (54%) children were of an ethnic minority background, and the mean duration of symptoms was relatively long at 14.2 months. The mean height and weight SDS were 1.09 (±1.38) and 0.86 (±1.2) respectively. Although boys tended to be smaller, the mean BMI SDS was comparable (boys 0.83; girls 0.93). The majority of children presented with axillary hair stage 1 (84%) and pubic hair stage 2 (54%). Body odour was also a complaint in 54% of cases. Whilst all male patients were pre-pubertal, 26% of the older girls (mean age 9.13 years) had evidence of breast development. Most (89%) children had their 17 hydroxyprogesterone (mean 4.08±2.2 nmol/L) measured. Other adrenal androgens and testosterone levels were normal in all patients who were tested. Only a minority had gonadotrophins (40%) and bone age (46%) estimated. We proceeded to a Synacthen test in only three children (basal 17 hydroxyprogesterone levels of 2.3, 7.8 and 12.3 nmol/L). No underlying pathology was identified in any of these children, and the average length of follow-up was 5 months. Conclusion Our audit demonstrates that parental concern over secondary sexual hair growth is a relatively common presentation in paediatric clinics. It is more common in girls presenting in a pre-pubertal state, with a small subset of older girls who may be pubertal with an antecedent history of PA. Baseline endocrine profile is reassuring in the vast majority and further dynamic testing is rarely needed. Our audit identified no underlying disease in this patient group.

Normal Pubertal Development: Part I: The Endocrine Basis of Puberty

1. Brian Bordini, MD* 2. Robert L. Rosenfield, MD* 1. *Section of Adult and Pediatric Endocrinology, The University of Chicago Pritzker School of Medicine, Chicago, IL. After completing this article, readers should be able to: 1. Explain how puberty is regulated by the hypothalamic-pituitary-gonadal axis. 2. Describe the hormonal interactions involved in pubertal development in boys and girls. Puberty is a defining developmental stage of every child's life, both physically and psychosocially. Concerns about the normalcy of pubertal development and menstrual patterns are among the most common questions posed to every physician caring for children. This article reviews the primary physiologic changes in the hypothalamic-pituitary-gonadal (HPG) axis and in adrenal androgen and growth hormone (GH) production that underlie the normal pubertal milestones. Understanding of these changes allows interpretation of laboratory data in children suspected of having pubertal abnormalities. Puberty is the developmental stage during which a child becomes a young adult, characterized by the maturation of gametogenesis, secretion of gonadal hormones, and development of secondary sexual characteristics and reproductive functions. Adolescence is used widely as a generally synonymous term for puberty, but the term often is used to convey an added connotation of cognitive, psychological, and social change. Thelarche denotes the onset of breast development, an estrogen effect. Pubarche denotes the onset of sexual hair growth, an androgen effect. Menarche indicates the onset of menses and spermarche the appearance of spermatozoa in seminal fluid. Gonadarche refers to the onset of pubertal function of the gonads, which produce most of the sex hormones that underlie the pubertal changes in secondary sex characteristics. Adrenarche refers to the onset of the adrenal androgen production that contributes to pubarche. ### The Hypothalamic-Pituitary-Gonadal Axis Normal puberty results from sustained, mature activity of the HPG axis. (1). The major hormones of the HPG axis are shown in Figure …

Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men.We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety.Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median).At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2 and 10.72 nmol/L, respectively.

Androgens and puberty.

Puberty is associated with an increasing production of androgenic steroids. Adrenal androgen formation, termed adrenarche, may precede gonadal testosterone synthesis. Both adrenal and gonadal androgens exert their biological effects via the androgen receptor, a nuclear transcription factor modulating a specific transcription regulation of largely unknown genes. During puberty, virilizing actions such as genital enlargement and sexual hair growth can be distinguished from anabolic action such as the gain in muscle strength and general changes in body composition. Furthermore, androgens play a major role in the initiation and maintenance of spermatogenesis. Thus, different androgenic steroids play an important role in the process of puberty. The control of their biosynthesis, their possible differential action on the molecular level, as well as the different target organs in males and females are discussed.

Isolated Absence of Adrenarche in A Postpubertal Female

Background The development of pubic and axillary hair (adrenarche) is part of the process of normal puberty. We report a case of isolated absence of adrenarche in a post-pubertal female. A review of the literature reveals no previously reported case of isolated absence of adrenarche in a postpubertal female. An investigation was understaken to evaluate the etiology of the lack of sexual hair growth in this patient. Case A 14 year-old postpubertal female presented complaining of heavy menstrual bleeding approximately four months after her first menstrual period. The patient had been previously diagnosed with a developmental delay and speech impediment by her referring physician. Further workup revealed a normal menstrual pattern, yet the physical examination was remarkable for the absence of axillary and pubic hair, as well as short stature. A complete evaluation was performed which included chromosome analysis, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione, testosterone, dihydrotestosterone (DHT), and 3-alpha androstanediol glucuronide. The serum androstenedione, testosterone, DHT, and 3-alpha androstanediol glucuronide levels were within normal limits. The DHEA-S levels were low yet adrenal function as analyzed by the Adrenocorticotropic hormone (ACTH) stimulation test was normal. Radiologic studies included pelvic ultrasound and bone age assessment with a bone age of 16 years. Skin biopsy of the mons pubis documents the presence of hair follicles. No previous or similar history has been noted in the patient's family history. Also of note, the patient is the product of a consanguineous relationship. Conclusion After review of our investigational findings, it is felt that this unique case likely represents an androgen receptor or post-receptor defect in the hair follicle.

Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate

Objective: To assess the efficacy of estrogen antagonist therapy on the function of the hypothalamic-pituitary-testicular axis in a young male runner with significant morbidity attributable to idiopathic hypogonadotropic hypogonadism. Design: An uncontrolled case study. Setting: The outpatient endocrinology clinic of a university tertiary referral center. Patient(s): A 29-year-old male who has run 50 to 90 miles per week since 15 years of age and who presented with a pelvic stress fracture, markedly decreased bone mineral density, and symptomatic hypogonadotropic hypogonadism. Intervention(s): Clomiphene citrate (CC) at doses up to 50 mg two times per day over a 5-month period. Main Outcome Measure(s): Serum concentrations of LH, FSH, and T before and after CC therapy, as well as clinical indicators of gonadal function. Result(s): Barely detectable levels of LH and FSH associated with hypogonadal levels of T were restored to the normal range with CC therapy. The patient experienced improved erectile function, increased testicular size and sexual hair growth, and an improved sense of well being. Conclusion(s): Exercise-induced hypogonadotropic hypogonadism exists as a clinical entity among male endurance athletes, and CC may provide a safe and effective treatment option for males with debilitating hypogonadism related to endurance exercise.

Androgens in the Aging Male

IN CONTRAST to the situation in women, where the menopause marks the end of the fertile period, in men fertility persists into old age. Nevertheless old age in men is accompanied by clinical signs, such as a decrease in muscle and bone mass, decrease in sexual hair growth, and decreased libido and sexual activity, suggesting decreased virility. These clinical signs are supported by histological evidence for a decreased Leydig mass and function. Evidence for decreased plasma testosterone in elderly men As to biochemical evidence for decreased androgenicity in elderly men, 25 yr ago the blood production rate of testosterone was reported to be decreased, which at least partially is caused by a decrease of the metabolic clearance. Whether or not aging is also associated with a decrease in plasma testosterone concentrations has long been highly controversial. Indeed, a large series of publications in the 1960s and early 1970s reporting decreased plasma testosterone concentrations in elderly

Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals--experiences with a novel androgen receptor blocker.

The effect of Anandron, a novel non-steroidal anti-androgen, on the reduction in sexual hair growth of 14 male-to-female transsexuals was investigated. Anandron (300 mg/day) alone for 8 weeks increased serum testosterone levels (mean: 19.2 +/- 6.1 to 44.9 +/- 11.5 mmol/l) and serum oestradiol levels (mean: 0.08 +/- 0.02 to 0.24 +/- 0.06 nmol/l). From Weeks 9 to 20, ethinyloestradiol (100 micrograms/day) was co-administered. Hair growth scores, hair weight and the number of terminal hairs decreased significantly in the first 8 weeks and continued to decrease during the second period in the areas assessed (the trunk and the limbs). In addition, there was a subjective decrease in hair growth on the limbs and the trunk, but not on the face. We suggest that Anandron alone and in conjunction with oestrogens is effective in reducing sexual hair growth on the limbs and the trunk.

9 Pilosebaceous physiology in relation to hirsutism and acne

PSAs, with few exceptions, consist of a piliary and a sebaceous component. In androgen-sensitive areas, each has the capacity to develop into either a terminal hair follicle or a sebaceous follicle depending upon its location. Without androgen, there is no development of the sexual hair follicle or sebaceous gland. Androgens appear to promote sexual hair growth by recruiting a population of PSAs that have preset genetic sensitivity to initiate the production of terminal hairs. The site of action of androgens within the PSA is unclear. There are indications that androgens may act at more than one site in a system that requires two-way reciprocal interaction between dermal and epithelial cells for the generation of hair growth. Growth hormone appears to exert an important synergism with androgen in affecting the PSA, seemingly through the mediation of insulin-like growth factors. Hirsutism is due to an increased density of growing terminal hairs. The majority of cases of moderately severe hirsutism in women are due to hyperandrogenaemia, as are half the cases of mild hirsutism and about one-quarter of the cases of mild acne vulgaris. We advocate reserving the term idiopathic hirsutism or idiopathic acne for those patients in whom excessive growth of terminal hair or acne is not explained by androgen excess. We believe that highly variable sensitivity to androgen within the population explains both idiopathic hirsutism and cryptic hyperandrogenaemia; that is, these disorders lie at opposite ends of the normal spectrum of sensitivity to androgen. The biological basis for the variations in responsiveness of PSAs to androgens is unknown. The regression of hirsutism induced by antiandrogen treatment is characterized by the growth of hairs that are more vellus in character, i.e. smaller and less medullated.

Premature adrenarche. Clinical and diagnostic features.

Premature adrenarche (PA) or isolated growth of sexual hair in young children, is a benign condition that may initially be confused with true precocious puberty or pathologic virilizing disorders. The clinical findings, family history, and serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were compared in 24 children with PA (79% black females) seen in a 2-year period and in an age-matched control group of 17 black females. Twenty three of 24 patients, but none of the controls, had an adult-type axillary odor. There was a positive family history of PA in only three of 24 children with PA, and in one of 17 controls. The mean serum DHEA-S was significantly higher in the PA children than in the controls, but there was a broad range of concentrations (10-143 micrograms/dl), with values in 10 of 24 cases falling within the control range for age. We conclude that: (1) PA is a relatively common finding in black females between ages 3 and 8, (2) an axillary odor is almost always present in children with PA, and (3) determination of serum DHEA-S may be of some help in confirming the clinical impression of a modest increase in adrenal androgen secretion and in ruling out a more serious disorder. In most cases, however, the diagnosis of PA can be made on the basis of the history, physical examination, and lack of rapid progression over time; the use of laboratory tests to rule out a pathologic virilizing process may best be reserved for those children with very early onset, increased linear growth, or other signs of virilization.

Plasma levels of FSH and LH in patients with gonadal dysgenesis during sequential estrogen and progestogen therapy.

We describe the plasma levels of FSH and LH in ten patients with gonadal dysgenesis during treatment with a low dosage sequential estrogen-progestogen preparation. The daily dose of mestranol ranged from 12.5--50 microgram. Norethisterone was administered from day 16 onwards, the dose ranging between 0.75 and 1.5 mg. It was shown that 25 microgram mestranol was effective in lowering the elevated FSH levels significantly (alpha < 0.001). LH levels remained unaffected. The combination of 25 microgram mestranol and 1 mg norethisterone produced an increase of FSH and LH within 12 h, maximum levels being reached within 36 h after which there was a progressive decline. Low doses of estrogen and progestogen appeared capable of evoking physiological hypothalamic and pituitary responses in patients with gonadal dysgenesis. The doses employed were sufficient to induce breast development, growth of sexual hair, and withdrawal bleeding and were probably not high enough to induce rapid bone maturation and consequent stunting of growth.

Hair

The psychologic importance of hair to man is in inverse ratio to its physical function. Except for scalp hair and desultory areas of sexual hair, most of man's hair follicles are vestigial. Three problems of hair growth remain to be solved: (1) how the intermittent activity of hair follicles in both animals and man is controlled; (2) how the male hormone alters the hair cycle in human skin; and (3) why larger hairs are produced by testosterone in some areas of the body when in some individuals the hair follicles in the scalp regress. Studies in which skin grafts from rats of different ages were exchanged showed that hair follicles are innately programmed but can be slowly influenced by systemic factors. Steroid hormones, especially estrogens, slow down the moult cycle whereas thyroid hormones accelerate it. What establishes the innate rhythm remains problematical. The fact that plucking out the club hair initiates activity in resting follicles has been explained by the hypothesis that the mitotic inhibitor which accumulates during anagen is normally used up or dispersed during telogen or by wounding. However, contrary to this theory, follicular activity is not prolonged by epilation during anagen. Moreover, if rats are epilated within one or two days of eruption, only club hairs are removed since forceps cannot grasp the tips of the new hairs. Such epilation does not affect the anagen in progress, but remarkedly enough the subsequent resting phase is shortened. Both sexual hair and male-pattern baldness depend on androgenic hormones. Target organs of testosterone convert the hormone to active metabolites, chiefly 5alpha-dihydrotestosterone. In skin, however, 5alpha-dihydrotestosterone may not be the only active tissue androgen. The major metabolite of testosterone incubated with hair roots in androstenedione, and hirsute women without other obvious endocrine abnormality sometimes excrete high levels of androstanediol. Both steroids stimulated the sebaceous glands of hypophysectomized-castrated rats, which, however, showed only a limited response to testosterone. The androgenic steroids, the enzymes that convert them to their active metabolites, and the proteins that bind them are undoubtedly very important to the problems of the growth of sexual hair and male-pattern baldness.

Hirsutism in Adolescent Girls

Abnormal sexual hair growth may result from excessive production of androgens or factors sensitizing the hair follicle apparatus to normal levels of endogenous androgens. Hirsutism may be encountered in endocrinologic disorders involving adrenals and ovaries, pituitary disorders which stimulate the adrenals or ovaries, and thyroid troubles. The most important laboratory test is the estimation of urinary 17-ketosteroids before and after adrenal suppression.

ANDROGEN METABOLISM.

THE TERM "ANDROGEN" operationally defines a class of substances that possess certain biological activities. Among these activities are the maintenance of the structure and function of the prostate and seminal vesicles, production of the pattern of sexual hair growth characteristic of the male, increase in the sex drive of the male animal, and promotion of muscular development. Many synthetic steroids have all of these properties and are therefore androgens. Although several naturally occurring steroids are androgenic in varying degrees, depending on the bioassay system used, it is the present consensus that the physiologically important androgen in man is testosterone. The introduction of new analytical methods has resulted in a rapid expansion of our knowledge of testosterone metabolism. We shall summarize these data and try to focus current concepts on problems in clinical medicine. We have limited this discussion to studies in man and a few relevant experiments with animals. For

“PREMATURE THELARCHE” AND ‘PREMATURE METRARCHE“ FOLLOWED BY NORMAL ADOLESCENCE

Summary A case report is presented of a healthy girl who, between 6 and 12 years of age, experienced 2 phases of sexual change with a silent interval between them. Phase I lasted from 6 to 7 4/12 years of age and was characterized by an isolated subliminal estrogenic response of mammary tissues and uterine mucosa. The latter response, consisting of irregular vaginal bleedings, occurred only during the first 3 months and ceased following an infection with measles. This phase was termed “premature thelarche and metrarche”. The absence of sexual hair growth, of a somatic growth spurt, of positive estrogen laboratory tests, and of any other demonstrable cause for the premature vaginal spottings appeared to confirm the diagnosis. There followed an interphase, from 7 4/12 to 9 years, of complete absence of all sexual phenomena. Between 9 and 12 years a perfectly regular picture of “early normal” adolescent maturation was observed, with the menarche at 11 years of age (Phase II).

“Premature thelarche” and “Premature metrarche” followed by normal adolescence

Summary A case report is presented of a healthy girl who, between 6 and 12 years of age, experienced 2 phases of sexual change with a silent interval between them. Phase I lasted from 6 to 7 4/12 years of age and was characterized by an isolated subliminal estrogenic response of mammary tissues and uterine mucosa. The latter response, consisting of irregular vaginal bleedings, occurred only during the first 3 months and ceased following an infection with measles. This phase was termed “premature thelarche and metrarche”. The absence of sexual hair growth, of a somatic growth spurt, of positive estrogen laboratory tests, and of any other demonstrable cause for the premature vaginal spottings appeared to confirm the diagnosis. There followed an interphase, from 7 4/12 to 9 years, of complete absence of all sexual phenomena. Between 9 and 12 years a perfectly regular picture of “early normal” adolescent maturation was observed, with the menarche at 11 years of age (Phase II).

Observations on the role of androgens and estrogens in body balance.

The increased growth of the body as a whole at the time of sexual maturation early suggested a causal interrelationship of these two phenomena. This was further emphasized by the development of precocious puberty in association with gonadal tumors. In this situation a rapid increase in body weight and height, maturation of the musculature and skeleton, deepening of the voice, and growth of sexual hair may be observed together with precocious development of the genitalia. When the gonadal steroids became available for study in man, Kenyon and his co-workers1demonstrated that testosterone propionate exerts anabolic effects on tissues other than those of the genital system. Thus a person eating a constant diet may gain as much as 9 kg. in body weight during testosterone administration, which is more than can be accounted for by growth of the genitals. Metabolic balance studies have shown that under the influence of androgenic

PRECOCIOUS GROWTH OF SEXUAL HAIR WITHOUT OTHER SECONDARY SEXUAL DEVELOPMENT; "PREMATURE PUBARCHE," A CONSTITUTIONAL VARIATION OF ADOLESCENCE

GROWTH of sexual hair in a young child suggests the possibility that adrenal tumor or hyperplasia may be causing virilization or that true sexual precocity may be beginning. However, neither of these relatively serious conditions may exist. Approximately 10 years ago workers in the Endocrine Clinic of the Harriet Lane Home became aware of the fact that sexual hair may appear in early life long before there is any other secondary sexual development dependent upon either androgen or estrogen. Although this syndrome has been referred to briefly in textbooks as "precocious adrenarche" and "premature pubarche," no detailed studies of a series of cases have been recorded. The present report is based on a study of 29 children who developed sexual hair before the age of 8 years. It was possible to follow a number of these patients long enough to demonstrate that the condition is a benign variation in the pattern of sexual development and is followed later by normal adolescence. It seems important to bring the findings to the attention of pediatricians who may not be familiar with the syndrome and to discuss its differential diagnosis and probable etiology. Methods Urinary 17-ketosteroids (17-KS) were determined by a modification of the method of Callow, Callow and Emmons previously described, urinary estrogens were measured as the "fluorogenic phenols" by the method of Jailer. Vaginal smears stained by the method of Shorr were interpreted as described elsewhere. The "bone age" was based on the average epiphysial development at all the joints. Clinical and Laboratory Findings