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Levels of estrogen and progesterone shift unevenly and unpredictably through perimenopause, causing hormonal symptoms, which include: Irregular periods and reduced fertility Hot flashes Insomnia Night sweats Changes in mood: depression, mood swings, and irritability Changes in sexual function: vaginal dryness and atrophy, painful intercourse, low libido, reduced sexual arousal, difficulty achieving orgasm Weight gain Breast tenderness Brain fog, forgetfulness, and difficulty concentrating (7, 30) Reductions in estrogen levels are also associated with increased risk for vaginal and urinary tract infections, osteopenia, osteoporosis, dyslipidemia, and heart disease (39)
Studies in the 1960s revealed that 4-hydroxy-l-proline is derived from the post-translational hydroxylation of l-proline in proteins (primarily collagen)
CB-839 was very well tolerated in heavily pretreated patients, with mostly mild (grade 1 or 2) adverse effects such as nausea, fatigue, photophobia, mild liver function elevation, diarrhea, and rash [170]