18 y.o. female with amenorrhea. Olesya Krivospitskaya, MD Endorama 08/08/2013
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1 18 y.o. female with amenorrhea Olesya Krivospitskaya, MD Endorama 08/08/2013
2 History of past illness: 18 y.o. female presented for the evaluation of a secondary amenorrhea Menarche at 12 Irregular menstrual cycles between y.o. (10 cycles per year) Stopped having menstrual cycles at 14 and no cycles since then Reports a hx of acne on her face, upper chest, upper back since13 y.o. Gained 40 lbs since that time and developed stretch marks on her abdomen
3 Past medical history: Past medical history: bipolar disorder diagnosed at the age of 14 Home medications: Depakote-ER, Risperdal, Vilazodone (Vibrid), Melatonin, Guanfacine (Intuniv ER) Family history: Paternal grand grand father with DM2, no fertility problems in her family. Social history: high school student, has younger brother and sister both healthy. No smoking, alcohol or illegal drugs.
4 Review of systems: Constitutional: gained 40lbs in the last 4 years. Sedentary lifestyle. Cardiovascular: palpitations in her chest mostly on exertion, but occasionally at rest. Genitourinary: secondary amenorrhea for the last 4 years. No galactorhea. Musculoskeletal: no weakness. Skin: stretch marks on her abdomen, pale, they appeared with a weight gain. Acne on her face, upper chest and back. No hirsutism. Psychiatric: anxiety, dysphoric mood.
5 Physical exam: Vitals: BP 107/73, pulse, Ht cm, Wt kg, BMI kg/m2 NEENT: Normocephalic, PERLA. Neck: Supple. No thyromegaly or nodules palpated. Cardiovascular: Regular rhythm and rate. No murmurs appreciated. Intact distal pulses. Respiratory/Chest: Normal respiratory effort. No wheezes or crackles. Gastrointestinal/Abdomen: Soft. Nontender. Bowel sounds are normal. She exhibits no distension and no mass. Musculoskeletal/extremities: No weakness, normal range of motion. Neurological: AAOx3. Normal DTRs. Skin: Acne face, upper chest and upper back. No significant hirsutism. Stretch marks on her abdomen, less than 0.5cm in diameter, pale color.
6 Labs: CMP from OSH was reviewed and was unremarkable TSH 3.11 (0.3-4 mcu/ml) Free T ( ng/dl) Anti-TPO and TG antibodies are negative Estradiol 25 ( pg/ml) LH 9.4 miu/ml Total testosterone 28 (20-60 ng/dl) Free testosterone 12 (3-9 pg/ml) Te binding globulin 14 ( nmol/l) Valproic acid 76 ( mcg/ml) Urine pregnancy test is negative FSH 4.8 miu/ml Prolactin ( ng/ml)
7 Impressions: Does the patient has PCOS?
8
9 PCOS and Bipolar Disorder PCOS-like symptoms and hyperprolactinemia in females treated with antiepileptic agents and antipsychotics Possible mechanisms of PCOS-like symptoms
10 Bipolar disorder and PCOS 34.2% of females with bipolar disorder report menstrual abnormalities¹ Some authors report that the association between PCOS and bipolar disorder could be related to the use of antiseizure and antipsychotic medication in this population² ¹ Joffe H, Kim DR, Foris JM, Baldassano CF, Gyulai L, Hwang CH, McLaughlin WL, Sachs GS, Thase ME, Harlow BL, Cohen LS. Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls. J Clin Psychiatry Feb;67(2): ² Joffe H, Hayes FJ. Menstrual cycle dysfunction associated with neurologic and psychiatric disorders: their treatment in adolescents. Ann N Y Acad Sci. 2008;1135:
11 Valproic acid and PCOS Joffe H, Hayes FJ. Menstrual cycle dysfunction associated with neurologic and psychiatric disorders: their treatment in adolescents. Ann N Y Acad Sci. 2008;1135:
12 Valproic acid and PCOS O'Donovan C, Kusumakar V, Graves GR, Bird DC. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry Apr;63(4):
13 Joffe H, Cohen LS, Suppes T, McLaughlin WL, Lavori P, Adams JM, Hwang CH, Hall JE, Sachs GS. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry Jun 1;59(11): Epub 2006 Jan 31.
14 PCOS features in adolescents taking valproic acid PCOS features develop more commonly among those who are younger when valproate treatment is begun. Among adolescents and adult women (13 40 years) with epilepsy who were randomized to valproate, hyperandrogenemia and ovulatory dysfunction developed in 44% of women years old, but only in 24% of those who were over 25 years old when they started valproate treatment.¹ Other studies in epilepsy have found polycystic ovarian morphology and/or an elevated testosterone level in 80% of women who started taken valproate before age 20.² ¹ Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, Warnock CR, Isojärvi J. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol Aug;64(2): ² Isojärvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllylä VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med Nov 4;329(19):
15 PCOS features in adolescents taking valproic acid Given that postpubescent girls have a high incidence of anovulation, it is possible that the relative immaturity of the HPG axis at this time period makes it more vulnerable to perturbation. Joffe H, Hayes FJ. Menstrual cycle dysfunction associated with neurologic and psychiatric disorders: their treatment in adolescents. Ann N Y Acad Sci. 2008;1135:
16 Mechanisms of proposed hyperandrogenism by valproic acid Verrotti A, D'Egidio C, Mohn A, Coppola G, Parisi P, Chiarelli F. Antiepileptic drugs, sex hormones, and PCOS. Epilepsia Feb;52(2):
17 Antipsychotic medications and hyperprolactinemia Antipsychotic medications, that work as D2 dopamine receptor antagonists, are associated with hyperprolactenemia secondary to reduced dopaminergic inhibition of prolactin secretion. Henderson DC, Doraiswamy PM. Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. J Clin Psychiatry. 2008;69 Suppl 1:32-44.
18 Antipsychotic medications and adverse events Henderson DC, Doraiswamy PM. Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. J Clin Psychiatry. 2008;69 Suppl 1:32-44.
19 Antipsychotic medications and metabolic effects Henderson DC, Doraiswamy PM. Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. J Clin Psychiatry. 2008;69 Suppl 1:32-44.
20 Take home points: PCOS is more prevalent in patients with bipolar disorder that in general population PCOS-like symptoms in patients with bipolar disorder could be related to use of antiseziure medications and antipsychotics There is little data exist about the management of PCOS-like symptoms in this population, tapering or switching the offending medication should be attempted when possible
21 References Joffe H, Kim DR, Foris JM, Baldassano CF, Gyulai L, Hwang CH, McLaughlin WL, Sachs GS, Thase ME, Harlow BL, Cohen LS. Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls. J Clin Psychiatry Feb;67(2): Joffe H, Hayes FJ. Menstrual cycle dysfunction associated with neurologic and psychiatric disorders: their treatment in adolescents. Ann N Y Acad Sci. 2008;1135: O'Donovan C, Kusumakar V, Graves GR, Bird DC. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry Apr;63(4): Joffe H, Cohen LS, Suppes T, McLaughlin WL, Lavori P, Adams JM, Hwang CH, Hall JE, Sachs GS. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry Jun 1;59(11): Epub 2006 Jan 31. Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, Warnock CR, Isojärvi J. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol Aug;64(2): Isojärvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllylä VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med Nov 4;329(19): Verrotti A, D'Egidio C, Mohn A, Coppola G, Parisi P, Chiarelli F. Antiepileptic drugs, sex hormones, and PCOS. Epilepsia Feb;52(2): Henderson DC, Doraiswamy PM. Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. J Clin Psychiatry. 2008;69 Suppl 1:32-44.
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