4: Hyperandrogenic Disorders (PCOS) Flashcards
T/F Glitazones lower glucose levels by increasing the utilization of glucose, which decreases hepatic glucose synthesis. Because of this, they are recommended when metformin does not work.
False. They are not recommended for use in PCOS.
What is the hallmark feature of PCOS?
Menstrual irregularity
_____ is a pure antiandrogen without progestogenic effects that has shown some benefit in treating hirsutism. Unfortunately, this medication is associated with hepatotoxicity that can cause liver failure and rarely death. It is not recommended for hirsutism treatment.
Flutamide is a pure antiandrogen without progestogenic effects that has shown some benefit in treating hirsutism. Unfortunately, this medication is associated with hepatotoxicity that can cause liver failure and rarely death. It is not recommended for hirsutism treatment.
In contrast to hirsutism, circulating androgens can also cause this.
Alopecia
If a virilizing tumor is suspected but an adnexal mass is not palpable, what is the procedure?
Transvaginal US. If no ovarian tumor is identified, adrenal CT should be performed. Routine adrenal imaging should be avoided because it can lead to unnecessary evaluation of nonfunctioning adrenal masses (incidentalomas).
A rapid progression of which PCOS symptoms is cause for concern for a possible androgen-producing tumor?
- Increased libido
- Increased muscle bulk
- Voice deepening
- Breast atrophy
- Clitoromegaly
Why would bleeding be heavy in PCOS?
Bleeding is generally irregular and unpredictable, and can be heavy as a result of continuous estrogenic stimulation of the endometrium and resultant endometrial hyperplasia.
Onset of breast development.
Thelarche
How long does it take for COC use to help with PCOS?
The maximal effect of COCs on acne is usually observed within 2 months. In contrast, the maximal effect on hair growth may take as long as 9 to 12 months for its realization because of the length of the hair growth cycle. COCs as monotherapy may be insufficient to treat hirsutism.
A dose of 5 mg/day is effective in treating hirsutism without engendering any adverse effects.
Finasteride
T/F Insulin resistance in PCOS is a problem of obesity.
False. Insulin resistance occurs in both normal-weight and overweight women with PCOS, but its frequency and magnitude are increased in obese women with PCOS.
These medications work by inhibiting gonadotropin secretion and subsequent ovarian hormone secretion, which results in not only a slowing of hair growth, but also severe estrogen deficiency.
Gonadotropin-releasing hormone (GnRH) analogs
T/F Insulin resistance can contribute to hyperandrogenism.
True. Increased insulin levels stimulate androgen production in the ovaries, both in isolation and by potentiating LH, and suppress SHBG production in the liver. A vicious cycle is created in which the elevated androgens and insulin suppress SHBG synthesis, resulting in an increase in free testosterone, which in turn exacerbates the insulin resistance.
T/F Women with PCOS are unable to conceive without fertility interventions.
False. More than half of women with PCOS are fertile (i.e., they will become pregnant within 12 months of trying), although it may take them longer to conceive.
When would the criteria for polycystic ovaries not apply in women with PCOS?
Women who take COCs because they can modify ovarian morphology.
T/F Antiandrogens are effective in the treatment of hirsutism. When used with COCs, they are more effective than either med alone.
True
Why has PCOS been designated a non-modifiable risk factor for PCOS?
Women with PCOS have:
- 2x the odds of impaired glucose intolerance
- 4x the odds of DMT2
Cycle length greater than 199 days.
Amenorrhea
What are the major circulating androgens found in women?
- Dehydroepiandrosterone sulfate (DHEA-S)
- Dehydroepiandrosterone (DHEA)
- Androstenedione
- Testosterone
- Dihydrotestosterone (DHT), which is the active metabolite of testosterone.
What scale is used to measure hirsutism and what number corresponds with it?
- Ferriman-Gallwey
- 8 or greater in general
- 9 or greater for Mediterranean
- 2 or greater for Asian
Finasteride is considered when COCs and spirolactone are ineffective for hirsutism. However, it must be used with contraceptives. What sort of teratogenic effect does it have?
Affect the development of the genital tract in male fetuses.
How does SHBG play a role in PCOS?
The bioactivity and androgenicity of testosterone are determined by sex hormone–binding globulin (SHBG). Circulating testosterone is bound to SHBG, which is produced in the liver. It is normal for approximately 80% of circulating testosterone to be bound to SHBG, 19% to be loosely bound to albumin, and the remaining 1% to be left unbound. The unbound, free testosterone is mainly responsible for androgenicity, although the fraction associated with albumin makes some contribution to this condition. SHBG levels are increased by estrogens and thyroid hormone, and suppressed by androgens and insulin. Therefore, in the presence of high levels of thyroid hormone or estrogen, more testosterone is bound, making less biologically available. If SHBG is suppressed or androgen production increases, the amount of free (unbound) testosterone will increase without necessarily increasing the total testosterone level, and the woman may develop symptoms of hyperandrogenism. Thus, because of the interplay among SHBG, insulin, thyroid hormone, estrogen, and androgen production, the total testosterone concentration may remain in the normal range, with symptoms reflecting only the decreased binding capacity of the SHBG and the increased percentage of unbound testosterone.
When trying to diagnose PCOS, which labs tests are necessary?
All women who have hyperandrogenism with ovulatory dysfunction should have:
- serum prolactin (r/o hyperprolactinemia)
- serum thyroid-stimulating hormone (TSH) (r/o thryoid disorders)
- fasting lipid profile (increased risk for lipid disorders)
- 2-hour oral glucose tolerance test (increased risk for DMT2)
- free testosterone (some agree, some think to reserve only for mod/severe hirsutism, sudden/rapid hirsutism, and signs of virilization)
- 17-OHP (r/o congential adrenal hyperplasia)
- Anti-Mullerian hormone (AMH) (esp when accurate US is not available. 4.5+ ng/mL are associated with PCOS).
- Women who have hyperandrogenism signs but regular menstrual cycles should have a serum progesterone level (between days 20-24 of cycle).
- Women who have signs of Cushing syndrome (buffalo hump, moon face, abd striae) need screening: 1 mg of dexamethasone orally between 11 p.m. and 12 a.m., and then drawing a serum cortisol at 8 a.m. the next morning. Values less than 1.8 mcg/dL are considered normal.
What are the most common side effects of metformin and which is the most serious?
- The most serious side effect of metformin is the development of lactic acidosis, although this is rare.
- Vitamin B12 deficiency can also occur.
- Gastrointestinal side effects, which are more common, include nausea, abdominal discomfort, diarrhea, and anorexia