Womens Early Years. Nayan Patel PharmD

Womens Early Years. Nayan Patel PharmD

Dr. Katharina Dalton (OBGYN) Treating PMS since 1953 with Dr. Greene (Endocrinologist) This is the 6 th edition published in 1999

Definition * PMS - is a group of physical, mood- related, and behavioral changes that occur in a regular, cyclic relationship to the luteal phase of the menstrual cycle and interfere with some aspect of the patient s life * PMDD - identifies women with PMS who have more severe emotional symptoms (such as anger, irritability, and depression) that may require more extensive therapy

Definition PCOS * A hormonal disorder, becoming obvious after puberty, in women of reproductive age - Named for the finding of small cysts developing in the outer edge of each ovary. https://www.womenshealth.gov/publications/our- publications/factsheet/images/pcos1.jpg

Incidence * PMS symptoms - 75%- 85% of women * Severe/debilitating PMS - 5-10% of women * PMDD - 3-5% of women * PCOS - The most common endocrine dysfunction of women - affects 10-20% of women * High risk for diabetes and metabolic syndrome & 80% are overweight/obese

Menstrual Cycle

Spectrum of Premenstrual Syndromes Severe (PMDD) Premenstrual Syndrome Severity Moderate (PMS) Mild (PMS) None Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 36 (387).

PMS/PMDD Symptoms Somatic symptoms * Breast tenderness * Abdominal bloating most common, occurs in 90% * Headache * Swelling of extremities * Weight gain

PMS/PMDD Symptoms Affective symptoms * Depression * Angry outbursts * Irritability * Anxiety * Confusion * Social withdrawal * Decreased concentration * Sleep disturbance * Appetite change/food cravings

Effects of PCOS Hormonal & Reproductive Effects * Hyperandrogens * Abnormal hormone receptors * Acne * Low libido * Hirsutism, alopecia * Pregnancy complications * Chronic anovulation * Infertility Metabolic Effects * Hyperinsulinemia * Insulin resistance * Impaired glucose tolerance * Fatty liver * Dyslipidemia * Endothelial dysfunction * Visceral obesity & overweight * Hypertension

PMS: Diagnosis * Patient reports 1 affective symptom and somatic symptom(s) during the luteal phase before menses * Symptoms relieved within 4 days of onset of menses, without recurrence until at least cycle day 13 * Symptoms occur in 2 consecutive menstrual cycles * Patient suffers from identifiable dysfunction in social or economic performance

PMDD: Diagnosis DSM- IV Criteria * Symptoms interfere with usual functioning and relationships * Symptoms are not an exacerbation of another disorder * Symptoms resolve at onset of menses * Premenstrual timing is confirmed by menstrual calendar in 2 consecutive cycles

PMDD: Diagnosis DSM- IV Criteria * At least 5 of 11 premenstrual symptoms * At least 1 of the following: * Depressed mood * Marked anxiety * Marked affective lability * Marked irritability * Other possible symptoms * Decreased interest in regular activities * Difficulty concentrating * Lethargy/fatigue * Appetite change/food cravings * Sleep disturbance * Feelings of being overwhelmed * Physical symptoms (bloating, weight gain, breast tenderness, edema)

PMS/PMDD: Differential Diagnosis Rule out other diseases: * Psychological disorders * Depression, Bipolar disorders, Personality disorders, Anxiety * Gynecologic disorders * Dysmenorrhea, Endometriosis, Pelvic Inflammatory Disease, Perimenopause * Endocrine disorders * Thyroid disease, Adrenal disorders, True hypoglycemia * GI conditions * Inflammatory bowel disease, Irritable bowel syndrome * Drug or substance abuse * Chronic fatigue states

PCOS: Diagnosis * High levels of Testosterone & DHEA * Is it inflammation & oxidative stress causing PCOS? * PCOS is related to other diseases like * Autoimmune diseases * Arthritis * IBS * Depression, anxiety & stress * Vaginal infections * Cancer * Sleep disturbances

PMS/PMDD: Treatment * Progesterone 150mg IM every other day from day 13 to 27 of cycle (Dr. Dalton used in 50 s) * Progesterone up to 400mg suppository from 1 QHS to 2 TID from day 13 to 27 of cycle (Dr. Dalton s protocol) * Always add probiotic and anti- fungal (saccharomyces boulardii) to any progesterone regimen.

PMS: Other Treatment (Medical) * NSAIDs * Anti- depressants * SSRI s (Fluoxetine or Sertraline) * Buspirone * Spironolactone bloating * Bromocriptine or Danocrine mastalgia * Ovulation suppression * GnRH agonists (e.g. Lupron) * Danazol * OCPs * SSRIs * (Can be taken throughout the cycle or during the luteal phase of the cycle) * Fluoxetine 20-60 mg qd * Sertraline 50-150 mg qd

PMSPMDD: Other Treatment (surgical) * Oophorectomy * Not generally recommended * Irreversible * Reserved for severely affected patients who only respond to GnRH agonists

PMS What to Avoid * Birth control pills. * Unopposed estrogen. * Situations that cause anovulatory cycles. * Sugar and refined carbohydrates. * Rancid unsaturated oils and hydrogenated oils. * Feed- lot meats (eat range- fed, organic meats free of drugs and pesticide residues). * Pesticides of all kinds. * Chronic stress.

PMS What to Do * Correct estrogen dominance with natural progesterone cream. * Take a daily multivitamin/mineral that includes * zinc, 10 mg; * B complex (all of the B vitamins); * vitamin C, 500-1000 mg; * magnesium, 300-400 mg; * vitamin E, 400 IU daily. * In addition, take Vitamin B6, 50 mg daily. * Eat a plant- based, fiber- rich diet of fresh, organic vegetables and fruits, nuts, seeds, whole grains, and legumes. * Eat fish at once or twice a week (check for Hg content).

PMS What to do? * Take evening primrose oil or borage oil to treat symptoms (equivalent to 300 mg GLA oils once or twice daily). * Take an herbal formula for PMS; Vitex, wild yam (Dioscorea). * Take a liver supporting and detoxifying herbal formula that includes some or all of the following herbs: milk thistle, barberry or goldenseal, burdock root, yellow dock, dandelion root. * Manage stress to avoid chronically high cortisol levels. * Get some exercise every day. * Keep a journal and allow yourself to record all the symptoms.

References PMS * APGO Medical Student Educa/onal Objec/ves, 9 th edi/on, (2009), Educa/onal Topic 49 (p104-105). * Beckman & Ling: Obstetrics and Gynecology, 6th edi/on, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 39 (p347-352, ). * Hacker & Moore: Hacker and Moore's Essen/als of Obstetrics and Gynecology, 5th edi/on (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 36 (p386-388). PMDD * APGO Medical Student Educa/onal Objec/ves, 9 th edi/on, (2009), Educa/onal Topic 46 (p98-99). * Beckman & Ling: Obstetrics and Gynecology, 6th edi/on, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 30 (p277-279). * Hacker & Moore: Hacker and Moore's Essen/als of Obstetrics and Gynecology, 5th edi/on (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 21 (p256-259).

Typical Rx for PMS * Progesterone 5 to 10% cream Sig: Apply 1 to 2 gms daily from day 13 to 27 of cycle After the initial high dose progesterone, it is advised to reduce the dose low enough to control the symptoms only and then eventually stop the therapy

PCOS Treatment * Progesterone 5% to 10% topical cream BID from day 13 to 27 of cycle. * Spironolactone 50mg QD to reduce androgen levels * Metformin XR 500mg to 1000mg BID to reduce insulin load. * Berberine 500mg to 1000mg BID to reduce insulin resistance. * Glutathione topical 100mg BID to reduce triglyceride levels secondary to hyperinsulinimia.

Progesterone Downstream Conversion Progesterone Cortisol Aldosterone T4 T3 Insulin Fluid retention Increased blood sugar

Case 1 * Patient: BM * Age: 26 years old - Female * Marital Status: Single * Occupation: Attorney

* Allergies: Sulfa * Medications, OTC, Vitamins: n/a * Medical Conditions: n/a * Cancer History/Family History: No personal or family history of breast, ovarian or uterine cancer- * Pregnancies: 1 child

* Alcohol: none * Tobacco: none * Caffeine: none

* Mammogram/Pap Smear: negative (within past 6 months) * Sexually active: Yes * Menstrual cycle: * Period lasts 4-6 days, heavy periods, irregular cycle (once every 2-3 months)

* Hot flashes 1/10 * Night sweats 2/10 * Vaginal Dryness 2/10 * Depression 3/10 * Fatigue 5/10 * Anxiety 4/10 * Irritability 7/10 * Insomnia 3/10 * Low Libido 1/10 * Fuzzy Thinking 5/10

Labs * Estradiol 70 pg/ml * Progesterone <0.5 ng/ml * Testosterone 35 ng/dl * DHEA- S 216 pg/ml * Vitamin D3 5 ng/ml

Treatment * Progesterone 75mg/ml 1ml inner thighs daily on day 14-28 of cycle * Vitamin D3 5000 IU 1 c po daily

Case 2 * Patient: BM * Age: 29 years old - Female * Marital Status: Married * Occupation: Chef

* Allergies: Sulfa * Medications, OTC, Vitamins: Vitamin B12, Multi- vitamin, Vitamin D3 * Medical Conditions: n/a * Cancer History/Family History: No personal or family history of breast, ovarian or uterine cancer- * Pregnancies: 1 child

* Alcohol: none * Tobacco: none * Caffeine: none

* Mammogram/Pap Smear: negative (within past 6 months) * Sexually active: Yes * Menstrual cycle: Period lasts 7 days, regular 28 day cycle

* Hot flashes 1/10 * Night sweats 0/10 * Vaginal Dryness 0/10 * Depression 10/10 * Anxiety 10/10 * Irritability 10/10 * Insomnia 3/10 * Low Libido 4/10 * Fuzzy Thinking 6/10 * Fatigue 3/10

* Estradiol 67 pg/ml * Progesterone 0.2 ng/ml * Testosterone 45 ng/dl * DHEA- S 167 mcg/dl * Vitamin D3 65 ng/ml

Treatment * Progesterone 400mg sup qhs from day 13 to 27 of cycle for 2 months and then evaluate. * Probiotics + saccharomyces boulardii take twice daily while on progesterone treatment.

Conclusion * All hormonal imbalance need to addressed within various gonadal hormones and try to mimic their natural cycle as possible. * Dose of the progesterone is dependent on the severity of the symptoms