IPFC 1 - NHPs in Menopause, Pregnancy & Lactation

Black cohosh (Cimicifuga racemosa) Uses

Use

• Relief of menopause symptoms

Products used for Relief of menopause symptoms

Black cohosh (Cimicifuga racemosa)

Soy Isoflavones

Red clover (Trifolium pratense)

Flaxseed

Evening primrose oil

Black cohosh (Cimicifuga racemosa) MOA

Mechanism of action

Estrogenic effects, SERM activity?

Serotonergic activity

Black cohosh (Cimicifuga racemosa) Cautions (CI, ADR, DIs)

Well-tolerated

CI – hypersensitivity, pregnancy, lactation

Caution with history of estrogen-dependent cancer (doesn't show proof of harm)

ADR – dizziness, GI upset, tremors, giddiness, case reports of hepatotoxicity

DI – case report of liver damage with atorvastatin; others – azathioprine, cyclosporine, tamoxifen

Black cohosh (Cimicifuga racemosa) Evidence

Possibly effective; accept, maybe recommend

• Evidence is mixed

• Many, but not all RCT (double-blind and open-label) support use of black cohosh for relief of menopausal symptoms

• Best evidence is with a brand (Remifemin) that has recently become available in Canada

• Likely less effective than HRT

• 2012 Cochrane review concluded no overall effect2

Soy isoflavones uses

• Treatment of menopausal symptoms, osteoporosis, hypercholesterolemia, etc.

Soy isoflavones MOA

• Isoflavones are phytoestrogens, which act as SERMs

• Soy protein found in food reduces LDL and total cholesterol (possibly soy isoflavones as well)

Soy isoflavones Cautions (CI, ADR, DIs)

• CI – hypersensitivity

• Safety in patients with breast cancer?

• ADR – well-tolerated; possible GI upset; concerns of endometrial hyperplasia

• DI – interaction between soy protein and MAO inhibitors due to tyramine content; soy-containing foods may reduce iron absorption

Soy isoflavones evidence

Likely less effective than HRT

Possibly effective: accept, maybe recommend

- Most studies saw modest reduction in frequency and severity of hot flashes and/or night sweats

- Soy isoflavones are generally favoured over placebo in reducing symptoms of menopause

Red clover (Trifolium pratense) MOA

• Contains isoflavones which are phytoestrogens

Red clover (Trifolium pratense) Cautions (CI, ADR, DIs)

CI – hypersensitivity, estrogen receptor-positive cancer?, pregnancy, lactation

ADR – well-tolerated; possible skin reactions

DI – increased risk of bleeding with anticoagulants, heparin, thrombolytics due to coumarin content; theoretically may alter activity of estrogen/progesterone

Endometrial hyperplasia?

Red clover (Trifolium pratense) Evidence

- mixed results, very few trials

- only Promensil seen as slightly effective

Insufficient reliable evidence; accept, maybe recommend

Flaxseed (eating the seeds) uses

• Menopausal symptoms, hypercholesterolemia, etc.

Flaxseed MOA

• Contains lignan constituents with estrogenic/anti-estrogenic activity

• Flaxseed oil is a source of alpha-linolenic acid, a precursor to DHA/EPA

Flaxseed Cautions

ADRs similar to increasing fibre intake (bloating, flatulence, abdominal pain, etc,)

Flaxseed evidence

- mixed results, only 1 RCT said effective

Insufficient reliable evidence; accept

Flaxseed dose

25-40 grams per day (trials have used muffins, bars with flaxseed or ground flaxseed)

• Note: flaxseed oil does not contain lignans (don't use for menopause)

Evening primrose oil use

Has been used for treatment of menopausal symptoms and premenstrual syndrome

Evening primrose oil MOA

Source of an omega-6 essential fatty acid, gamma-linolenic acid (GLA), which is believed to be the active ingredient

Evening primrose oil cautions

- Generally well-tolerated

- Occasional headache, abdominal pain, nausea, and loose stools

Evening primrose oil evidence

• Limited evidence for use on its own; small trials showed no effect; possible benefit with combination products

Insufficient reliable evidence; accept

St. John's Wort interaction and how it works

Interacts with oral contraceptives

• St. John’s Wort reduces concentrations of norethindrone and ethinyl estradiol through induction of CYP P450 (1A2, 2C9, 3A4) enzymes - faster drug metabolism

• Leads to breakthrough bleeding

• Cases of unplanned pregnancy have been

reported

• Alternative method of contraception should be used

Ginger (Zingiber officinale) Uses

Treatment of N/V associated with pregnancy, surgery, motion, sickness, chemo, etc.

Ginger (Zingiber officinale) MOA

Active ingredients – shogaol and gingerol

Anti-emetic properties possibly due to activity at serotonin receptors in GI tract

Ginger Cautions

- May prolong bleeding time (not well-documented)

- Mild GI upset – heartburn, diarrhea

- Use in pregnancy appears to be safe, unlikely to harm baby; does not appear to increase risk of malformations or adverse pregnancy outcomes (ex. spontaneous abortion)

Ginger Evidence

- Most RCTs support efficacy pregnancy-induced nausea/vomiting

- Comparable efficacy for pyridoxine, dimenhydrinate

• Slower onset of action than antihistamines (~3 days)

• Natural Medicines: “possibly effective”

• Accept, maybe recommend

Red Raspberry Leaf (Rubus idaeus) Uses

- May be used to facilitate labour/delivery (often used by midwives in late pregnancy)

- Often consumed as an herbal tea

Red Raspberry Leaf (Rubus idaeus) Cautions

- Possibly unsafe during early pregnancy (up to 32 weeks)

Red Raspberry Leaf (Rubus idaeus) Evidence

Not well-studied, but limited data suggests it does not reduce time in labour

"insufficient reliable evidence to date"

Accept (during late pregnancy only)

Fenugreek (Trigonella foenugraecum) Uses

• Widely used and recommended to promote lactation

• Approved in Canada with traditional use claims related to digestion, appetite

Fenugreek Cautions

Distinct maple odor

May affect glucose levels and blood clotting

Fenugreek Evidence

• Small amount of evidence supports increased breastmilk production

"insufficient reliable evidence - Accept"