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Clinical Obstetrics and Gynecology Dec 1991
Review
Topics: Female; Humans; Ovarian Diseases; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Virilism
PubMed: 1778025
DOI: 10.1097/00003081-199112000-00021 -
The Journal of Clinical Endocrinology... Apr 2021Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows... (Review)
Review
UNLABELLED
Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as "premature adrenarche." It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene.
LEARNING OBJECTIVES
Identify the precise pathophysiologic mechanisms leading to virilization in girls at puberty considering that virilization at puberty may be the first manifestation of an endocrine active tumor or a disorder/difference of sex development (DSD) that remained undiagnosed before and may be life-threatening. Of the DSDs, nonclassical congenital adrenal hyperplasia occurs most often.Provide a step-by-step diagnostic workup plan including repeated and expanded biochemical and genetic tests to solve complex cases.Manage clinical care of a girl virilizing at puberty using an interdisciplinary team approach.Care for complex cases of DSD manifesting at puberty, such as the presented girl with a Turner syndrome-like phenotype and virilization resulting from a complex genetic variation.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Female; Humans; Puberty; Virilism
PubMed: 33367768
DOI: 10.1210/clinem/dgaa948 -
The Journal of Clinical Endocrinology... Apr 2023Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other... (Review)
Review
Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment.
Topics: Female; Humans; Hyperandrogenism; Androgens; Diabetes Mellitus, Type 2; Postmenopause; Polycystic Ovary Syndrome; Virilism; Testosterone; Adrenal Gland Neoplasms
PubMed: 36409990
DOI: 10.1210/clinem/dgac673 -
American Journal of Physiology.... Jun 2021Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin...
Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (). Fasting blood was collected on , , , , and , and females were euthanized on . On , TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations () were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated and in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT. Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.
Topics: Adipose Tissue; Animals; Female; Injections, Intramuscular; Insulin; Insulin Resistance; Liver; Signal Transduction; Swine; Testosterone; Virilism
PubMed: 33900852
DOI: 10.1152/ajpendo.00281.2020 -
Ryoikibetsu Shokogun Shirizu 1993
Review
Topics: Adolescent; Adrenal Cortex Neoplasms; Adult; Androgens; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Virilism
PubMed: 7757651
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... May 2006
Review
Topics: Adrenal Cortex Neoplasms; Adrenalectomy; Androgens; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Mitotane; Prognosis; Virilism
PubMed: 16776254
DOI: No ID Found -
The American Journal of Medicine Sep 1992A 51-year-old woman with a virilizing adenoma and underlying undetected and untreated congenital adrenocortical hyperplasia is described. The 10 instances of the... (Review)
Review
A 51-year-old woman with a virilizing adenoma and underlying undetected and untreated congenital adrenocortical hyperplasia is described. The 10 instances of the combination of these two pathologic lesions are reviewed with particular attention to the steroid abnormalities encountered.
Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Female; Humans; Middle Aged; Virilism
PubMed: 1524088
DOI: 10.1016/0002-9343(92)90243-5 -
CMAJ : Canadian Medical Association... Apr 2023
Topics: Female; Humans; Postmenopause; Virilism
PubMed: 37094875
DOI: 10.1503/cmaj.220685-f -
American Journal of Obstetrics and... Jun 1995Virilizing adrenal carcinoma is a rare disease, especially in women of reproductive age. A young woman who was seen with hirsutism, virilization, and infertility had a... (Review)
Review
Virilizing adrenal carcinoma is a rare disease, especially in women of reproductive age. A young woman who was seen with hirsutism, virilization, and infertility had a well-differentiated adrenal cortical carcinoma. After treatment she conceived twice and currently is disease free 8 years after treatment. This case illustrates that adrenal carcinoma and its treatment need not eliminate a woman's reproductive potential.
Topics: Adrenal Cortex Neoplasms; Adrenalectomy; Adult; Carcinoma; Female; Hirsutism; Humans; Infertility, Female; Mitotane; Prednisone; Pregnancy; Virilism
PubMed: 7778652
DOI: 10.1016/0002-9378(95)91431-5 -
Journal of Medical Case Reports Dec 2022Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified...
BACKGROUND
Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical.
CASE PRESENTATION
We present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs.
CONCLUSION
The purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Amenorrhea; Polycystic Ovary Syndrome; Testosterone; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Virilism
PubMed: 36564842
DOI: 10.1186/s13256-022-03697-w