Polyendocrine Metabolic Ovarian Syndrome (PMOS)

Epidemiology and Pathophysiology

Epidemiology

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 8%–13% of reproductive-age women globally
• One of the most common causes of:
  • Oligomenorrhea 
  • Secondary amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System 
  • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
  • Hirsutism (abnormal facial and body hair growth)
  • The single most common cause of anovulatory infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility.
• 50%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are obese.

Pathophysiology

The exact mechanisms are unknown, but thought to be complex and include both genetic and environmental factors. Key contributors include genetic susceptibility, neuroendocrine dysfunction, ovarian hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics, insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus, and environmental influences.

• Polyendocrine metabolic ovarian syndrome (PMOS) includes:
  • ↑ Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
  • Chronic anovulation
  • Polycystic-appearing ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy
  • Metabolic dysfunction (commonly known as metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome):
    • Insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus
    • Dyslipidemia
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Associated with obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • ↑ Risk for diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus and cardiovascular disease
• Dysfunction in the hypothalamic-pituitary-ovarian axis Hypothalamic-pituitary-ovarian axis Gonadal Hormones:
  • ↑ Luteinizing hormone ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) level:
    • Stimulates testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens production in ovarian theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty
    • LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors tend to be over-expressed in polycystic ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy.
    • Cause of ↑ LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle: Persistently rapid gonadotropin-releasing hormone Gonadotropin-releasing hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Gnrh is produced by neurons in the septum preoptic area of the hypothalamus and released into the pituitary portal blood, leading to stimulation of gonadotrophs in the anterior pituitary gland. Puberty (GnRH) pulses → favor LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle secretion Secretion Coagulation Studies over follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) → ↑ LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle secretion Secretion Coagulation Studies
  • Follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle):
    • FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle stimulation is insufficient for ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle → abnormal follicle development
    • Evidence of FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing at the follicular level
  • Chronic unopposed estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy:
    • No ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle → ↓ progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones 
    • Results in endometrial proliferation without menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
    • ↑ Risk for endometrial hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation or carcinoma
• Hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics:
  • ↑ LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↑ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens:
    • ↑ Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin → sensitizes the ovary to LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • Theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty overexpress steroidogenic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes → ↑ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
  • Likely involves a genetic predisposition
  • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens secreted primarily from the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy and adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy
• Insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus and obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity:
  • ↑ Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin leads to:
    • ↑ Androgen production in ovarian theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty
    • ↓ Hepatic production of sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria hormone-binding globulin ( SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones) 
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity:
    • Adipocytes Adipocytes Cells in the body that store fats, usually in the form of triglycerides. White adipocytes are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. Brown adipocytes are thermogenic cells that can be found in newborns of some species and hibernating mammals. Adipose Tissue: Histology convert androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens → estrogens → ↓ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → worsening ovulatory dysfunction
    • ↑ Insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus → ↑ free testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens → ↑ hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics
    • ↑ Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome
    • Unclear whether obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity itself is causative in PMOS

Clinical Presentation

Polyendocrine metabolic ovarian syndrome (PMOS) should be suspected in any reproductive-age female with irregular menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle and/or symptoms of hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics, especially if obese or presenting with infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility.

Symptoms of hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics

• Hirsutism:
  • Excess terminal body hair
  • Male distribution:
    • Upper lip Upper Lip Melasma
    • Chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma
    • Periareolar
    • Linea alba
• Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris
• Male-pattern alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
• Early adrenarche (development of pubic hair, apocrine glands, and sebaceous glands)

Menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle irregularities

• Oligomenorrhea (cycle length > 35 days) 
• Amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System (cycles absent)
• Symptoms present for 3–6 months or 3 cycle lengths
• Due to chronic anovulation

Associated conditions

• Metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome:
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity (especially with ↑ waist:hip ratio)
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Impaired glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance tolerance Tolerance Pharmacokinetics and Pharmacodynamics:
    • Type 2 diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
    • Acanthosis nigricans Acanthosis nigricans A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. Diabetes Mellitus (marker of insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus)
  • Dyslipidemia
• Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
• Cardiovascular disease
• Endometrial hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation and carcinoma
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care complications (gestational diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus and preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders)
• Depression and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
• Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea

Diagnosis

Polyendocrine metabolic ovarian syndrome (PMOS) is a diagnosis of exclusion, so other causes of oligo- or amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System and hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics must be ruled out. The Rotterdam criteria are commonly used to make the diagnosis once other causes are excluded.

Rotterdam criteria

Diagnosis requires 2 of the 3 following criteria:

• Clinical and/or biochemical signs of hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics
• Oligo- or anovulation
• Polycystic ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy on ultrasound or an elevated anti-Müllerian hormone ( AMH AMH A glycoprotein that causes regression of mullerian ducts. It is produced by sertoli cells of the testes. In the absence of this hormone, the mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent mullerian duct, a form of male pseudohermaphroditism. Primary Amenorrhea) level
  • In adults, AMH AMH A glycoprotein that causes regression of mullerian ducts. It is produced by sertoli cells of the testes. In the absence of this hormone, the mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent mullerian duct, a form of male pseudohermaphroditism. Primary Amenorrhea may be used as an alternative to ultrasound, but should not be used as a single test for diagnosis.
  • In adolescents, neither ultrasound nor AMH AMH A glycoprotein that causes regression of mullerian ducts. It is produced by sertoli cells of the testes. In the absence of this hormone, the mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent mullerian duct, a form of male pseudohermaphroditism. Primary Amenorrhea should be used for diagnosis; diagnosis should rely only on hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics plus persistent ovulatory dysfunction.

Physical exam

• Hirsutism:
  • Male-pattern facial and body hair growth
  • Modified Ferriman-Gallwey score:
    • An objective evaluation of hirsutism
    • Often not helpful as some women remove unwanted hair
  • Consider normal ethnic variations in hair: Mediterranean, Middle Eastern, and South Asian (most hair) > Caucasian and Black > East Asian and Native American (least hair)
• Pelvic exam:
  • Mild ovarian enlargement
  • Rule out structural causes of abnormal bleeding.
• Signs of Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes (alternate diagnosis):
  • Moon face
  • Buffalo hump
  • Abdominal striae

Laboratory and imaging evaluation

• Urine human chorionic gonadotropin (HCG): rule out pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Assess other potential causes of abnormal bleeding:
  • Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH)
    • ↑ → hypothyroid
    • ↓ → hyperthyroid
  • ↑ Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy → hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia
• Assess for biochemical hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics (and other potential causes of hirsutism):
  • Free testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens: ↑ in PMOS
  • Dehydroepiandrosterone Dehydroepiandrosterone A major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (DHEA) can be converted to testosterone; androstenedione; estradiol; and estrone. Androgens and Antiandrogens sulfate (DHEA-S): ↑ in certain androgen-secreting adrenal tumors
  • 17-hydroxyprogesterone: ↑ in non-classic congenital adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation (NCCAH)
• Assess for metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome:
  • 2-hour glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance tolerance Tolerance Pharmacokinetics and Pharmacodynamics test 
  • Fasting lipid panel:
    • ↑ Triglycerides Triglycerides Fatty Acids and Lipids and low-density lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism (LDLs)
    • ↓ High-density lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism (HDLs)
• Other laboratory tests to consider:
  • Cycle day 3 LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle: FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle ratio → often > 2 in PMOS (normal is < 1)
  • 24-hour urinary free cortisol 24-Hour Urinary Free Cortisol Cushing Syndrome → screen for Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes
• Transvaginal ultrasonography:
  • “Pearls on a string” (also known as the pearl necklace sign): multiple antral follicles Antral follicles Ovaries: Anatomy at the periphery of the ovary
  • ↑ Ovarian volume
  • Neither ultrasound nor AMH AMH A glycoprotein that causes regression of mullerian ducts. It is produced by sertoli cells of the testes. In the absence of this hormone, the mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent mullerian duct, a form of male pseudohermaphroditism. Primary Amenorrhea is needed for diagnosis if irregular cycles and hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics are both present.

Management

General management

• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery:
  • Goal of 5%–10% weight reduction
  • ↓ Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy production in adipocytes Adipocytes Cells in the body that store fats, usually in the form of triglycerides. White adipocytes are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. Brown adipocytes are thermogenic cells that can be found in newborns of some species and hibernating mammals. Adipose Tissue: Histology → ↓ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle inhibition by estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → resumption of normal ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
  • ↓ Risk of metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome
• Regular Regular Insulin screening Screening Preoperative Care and treatment for:
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Dyslipidemia
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Cardiovascular disease
• Endometrial protection:
  • Goal is to ↓ risk of endometrial hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation or cancer.
  • Combined oral contraceptive pills Combined oral contraceptive pills Fixed drug combinations administered orally for contraceptive purposes. Hormonal Contraceptives (OCPs) → allows regular Regular Insulin withdrawal bleeding.
  • Levonorgestrel-containing intrauterine device (IUD) → endometrial suppression Suppression Defense Mechanisms
  • Intermittent or continuous progestin therapy

Hirsutism management

• Mechanical hair removal (e.g., waxing, laser hair removal)
• Combined OCPs:
  • ↓ LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens production in the ovary
  • ↑ SHGB → ↑ binding of testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens → ↓ free testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
  • ↓ DHEA-S in the adrenals
  • ↓ 5-α-reductase activity in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• Antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens:
  • Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics
  • Finasteride Finasteride An orally active 3-oxo-5-alpha-steroid 4-dehydrogenase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. Androgens and Antiandrogens
• Metformin Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Non-insulinotropic Diabetes Drugs:
  • No longer 1st line treatment for any PMOS indication
  • Used primarily for metabolic features: body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥ 25 kg/m², insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus, or glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance/lipid abnormalities
  • Still considered 1st line in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with type 2 diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin sensitizing agent: ↓ hepatic glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance production → ↓ insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin → ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens 
  • Despite ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens, there is limited reduction in hirsutism.

Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility management

• Letrozole Letrozole A triazole and benzonitrile derivative that is a selective non-steroidal aromatase inhibitor, similar to anastrozole. It is used in the treatment of metastatic or locally advanced breast cancer in postmenopausal women. Antiestrogens:
  • Aromatase Aromatase An enzyme that catalyzes the desaturation (aromatization) of the ring a of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the cyp19 gene, and functions in complex with NADPH-ferrihemoprotein reductase in the cytochrome p450 system. Adipose Tissue: Histology inhibitor
  • More effective at ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle induction and safer than clomiphene citrate Clomiphene citrate A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Antiestrogens in PMOS
  • Now considered the first-line pharmacologic treatment for ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle induction in PMOS, per major guidelines, despite not being FDA approved for this indication.
  • ↓ Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → ↓ inhibition of FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↑ follicular development → ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
• Clomiphene citrate Clomiphene citrate A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Antiestrogens:
  • A selective estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors modulator (SERM) 
  • FDA approved to treat infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
  • Inhibits effects of estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy at the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types → ↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↑ follicular development → ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
• In vitro fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week

Differential Diagnosis

• Non-classical congenital adrenal hyperplasia Non-classical Congenital Adrenal Hyperplasia Congenital Adrenal Hyperplasia (NCCAH): a less severe form of an inherited enzyme deficiency (usually 21-hydroxylase) resulting in decreased production of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia and cortisol Cortisol Glucocorticoids. Instead, precursors are shunted down the sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria steroid pathways, leading to increased androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will develop hirsutism, oligomenorrhea, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility. Elevated 17-hydroxyprogesterone is diagnostic for congenital adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation ( CAH CAH Congenital adrenal hyperplasia (CAH) consists of a group of autosomal recessive disorders that cause a deficiency of an enzyme needed in cortisol, aldosterone, and androgen synthesis. The most common subform of cah is 21-hydroxylase deficiency, followed by 11β-hydroxylase deficiency. Congenital Adrenal Hyperplasia), but will be normal in PMOS. Management involves antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens and glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids. 
• Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes: elevated cortisol Cortisol Glucocorticoids due to excess adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH) secretion Secretion Coagulation Studies, adrenal tumors, or exogenous steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors. Presentation is similar to PMOS with menstrual irregularities and hirsutism, as well as abdominal purple striae, truncal obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, and moon face. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can be screened with a 24-hour urine free cortisol Cortisol Glucocorticoids test or a dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics suppression Suppression Defense Mechanisms test. Management depends on the cause and includes withdrawal of exogenous steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, adrenal inhibitors, or surgery for tumors. 
• Exogenous testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens exposure: occurs when a man’s testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens cream is transmitted to a woman through contact exposure. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may develop hirsutism; diagnosis is based on history and elevated testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens levels.
• Ovarian tumors: sex-cord stromal tumors arising from the theca or granulosa cells within the ovary secreting androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens or estrogens, respectively. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have signs of virilization, irregular menstrual cycles, or abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding. Androgen and estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy levels tend to be more elevated than typically seen in PMOS. Initial treatment is surgical and based on the stage of malignancy Malignancy Hemothorax.
• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism: a thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone deficiency resulting in either oligo- or amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System, which may negatively impact fertility. Effects are likely due to structural similarities between TSH, FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, and LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, as well as associated decreases in SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones. Other symptoms include thinning of the hair, dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, brittle nails, periorbital Periorbital Orbital and Preseptal Cellulitis edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia. Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH) is increased due to low thyroxine Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroid Hormones. Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism is treated with levothyroxine Levothyroxine Thyroid Replacement Therapy. 
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care: results in amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System, though typically not causing hirsutism symptoms. Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care should be ruled out with a urine pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test when evaluating amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System. Treatment is obstetric care.