These cases of ovulatory dysfunction are linked to infertility and menstrual disturbances. A post hoc analysis from a randomized, placebo-controlled, multi-centre study carried out at 11 secondary care centres, as well as a longitudinal single-centre study on pregnant women in Norway, also determined that metformin had no effect on maternal androgens in pregnancies occurring in the setting of PCOS.One systemic review suggested that polymorphisms in the vitamin D receptor gene are associated with the prognosis of polycystic ovary syndrome, though this is based on small sample sizes and is debated. Studies have shown benefits for vitamin D supplementation in women with vitamin D deficiency and PCOS.Hyperinsulinemia can increase the production of androgens in the ovaries. One context in which this occurs is HAIR-AN syndrome, a rare subtype of PCOS. Hyperthecosis and hyperinsulinemia
Hyperthecosis occurs when the cells of the ovarian stroma transition from interstitial cells, located between other cells, into luteinized theca cells. Theca cells are located in the ovarian follicles and become luteinized when the ovarian follicle bursts and a new corpus luteum is formed. The dispersal of luteinized theca cells throughout the ovarian stroma — in contrast to their distribution in PCOS, in which luteinized theca cells occur around cystic follicles only — causes women with hyperthecosis to have higher testosterone levels and virilization) than women with PCOS. Elevated insulin is also characteristic of hyperthecosis. Hyperthecosis most commonly develops in postmenopausal women and is linked to acne, hirsutism, growth of the clitoris, baldness, and voice deepening.Obesity can play a role in insulin resistance.
Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the TOKU-Es product data sheet. According to the United States Centers for Disease Control, fluconazole resistance among Candida strains in the U.S. is about 7%. Contraindications
Fluconazole is contraindicated in patients who:
Drink alcohol
have known hypersensitivity to other azole medicines such as ketoconazole;
are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
take SSRIs such as fluoxetine or sertraline. Side effects
Adverse drug reactions associated with fluconazole therapy include:
Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes
Infrequent (0.1–1% of patients): anorexia, fatigue, constipation
Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions
Very rare: prolonged QT interval, torsades de pointes
FDA is now saying treatment with chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants.If taken during pregnancy it may result in harm.