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Nayan Patel, PharmD

HRT Dosing – Female Patients

Dr. Katharina Dalton (OBGYN)Treating PMS since 1953 with Dr. Greene (Endocrinologist)

This is the 6th edition published in 1999

Menstrual Cycle

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PMS/PMDD/Perimenopause: 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

PMS/PMDD: Other Treatment (surgical)• Oophorectomy

• Not generally recommended• Irreversible

• Reserved for severely affected patients who only respond to GnRH agonists

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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

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

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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

Other Related Treatment Considerations• Due to heavy blood loss and excess inflammation

• Methylcoabalamine 6.25mg• Hydroxocobalamine 6.25mg• Folinic Acid 5mg• P5P 6.25mg

Other Related Treatment Considerations• 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

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Menopause is Related to Health• Increased risk for developing two significant diseases: osteoporosis and heart disease

Managing Perimenopause - Goals• Patient education• Prevention of endometrial cancer• Individualized symptomatic relief

• Menstrual control• Minimizing hot flashes• Mood disturbances

Peri/menopause Treatment• Bio-identical hormones

• Estradiol• Estriol• Testosterone• DHEA• Pregnenolone• Cortisol• Thyroid• Insulin

• OTC herbs and supplements

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Peri/menopause Treatment –Factors to Consider • Daily vs Rhythmic hormonal treatment• What dosage form is right for your patient

• Capsules• Sublingual drops/tablets/troches• Topical/mucosal cream/gel• Transdermal cream/gel• Suppositories• IM injections

Dosage Forms• Capsules – swallow by mouth. Some may cause drowsiness and

some has huge 1st pass. May also increase metabolite concentration and have to be careful if they are toxic

• Suppository – can be used either rectally or vaginally • Sublingual drops/tablets/troches – must place under the

tongue until absorbed. (caution: part of the medication will be swallowed and taste will vary based on the dosage

• IM injections – Need to take weekly shots. No other added advantage

• Pellets – Minor surgical procedure required to insert the pellets and may last for 3 to 6 months (only for estradiol & testosterone)

Dosage Forms – Cont. • Topical creams – All creams has limitation as to the final

concentration of the cream • All creams are oil-in-water emulsions and depending on the oil phase of the cream

there is only so much hormones you can incorporate inside • The best area to apply the medication is as close to ovaries as possible (vaginally).• Cosmetically very appealing

• Transdermal creams – Most work on the concept of making small micelles with liposome and can incorporate larger concentration of hormones than creams

• Actively drives the medication through the skin• Takes a little longer to absorb and may not be cosmetically appealing (a little sticky)

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Dosage Forms – Cont. • Gel – most gels are alcohol based. Water based gel cannot

dissolve hormones and may not deliver hormones via skin.• Alcohol based gels may cause dry skin and cannot be used for vaginal

application • Ideal to delivery large amount of hormones• Fast absorbing and actively drives the medication through the skin

Typical Rx for Peri-Menopause• Progesterone SB (sacchromycesis boulardii) 150 to 200mg caps @

bedtime (if insomnia) OR• Progesterone 5 to 10% cream daily from day 13 to 27 of cycle• Biestrogen 0.625 to 1.25mg cream (only if low estradiol level

and symptomatic)• Androgen added if symptomatic and confirmed low hormone

levels

Typical Rx for Menopause• Biestrogen 1.25 to 2.5mg cream daily (Day 1 to 25)• Progesterone SB (sacchromycesis boulardii) 150 to 200mg

caps @ bedtime (Day 6 to 30)• Testosterone 0.5 to 1mg cream daily• Pregnenolone/DHEA 25/5 to 25/10mg caps daily

Also evaluate the need to regulate thyroid and adrenal function for optimum results

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Typical Rx for Menopause(secondary to hysterectomy)<45 yrs old vs. >45 yrs old• Progesterone 30 to 80mg topical cream

OR• Progesterone 100mg to 200mg SB daily at bedtime from day 13

to 27 of cycle/month• Biestrogen 0.625 to 1.25mg topically daily from day 1 to day 21

of cycle/month• Testosterone 0.5mg to 1mg topically daily• Pregnenolone/DHEA 25/5 to 25/10mg topically or orally daily

Conclusion• Pre & Post reproductive years in women life is about the same

number• Learning effective way to manage hormonal intervention can

dramatically improve quality of life• Managing of hormones need to take into account for all the

hormones from Cortisol, thyroid, insulin, gonadal, pituitary and hypothalamic hormones

• Strive to achieve proper endocrine balance for patients to feel the best

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

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