Natural Progesterone versus Progestins

Natural Progesterone is produced by your own body at the end of every cycle and in large amounts during pregnancy to maintain the pregnancy.  At the latter half of the menstrual cycle, your body usually produces 20-40 mg/day of Natural Progesterone.  During pregnancy, your body initially makes 20 mg/day of progesterone, then Natural Progesterone production increases gradually to 400 mg/day during one day of third trimester pregnancy.  The Natural Progesterone produced by your body does NOT create birth defects, and is safe for the mother and developing baby.  Natural Progesterone is also known as bioidentical progesterone.  This Natural Progesterone is found in Progestelle.

Side Effects of MedroxyProgesterone According to pdr.net

In contrast, according to drugs.com, medroxyprogesterone is a progestin, a brand name synthetic patented chemically modified progestin.  According to drugs.com medroxyprogesterone should not be used if you are pregnant because it can cause birth defects.  The site instructs, “Do NOT use medroxyprogesterone if you are pregnant.” 

Boxed Warning for Medroxyprogesterone Acetate

Here is the Boxed warning from pdr.net for medroxyprogesterone acetate:

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease (CVD) or dementia. Increased risk of deep vein thrombosis (DVT - blood clots in the legs), pulmonary embolism (PE - blood clots in the lungs), stroke, and myocardial infarction (MI - heart attack) reported in postmenopausal women (50-79 yrs of age) treated w/ daily oral conjugated estrogens (CEs - synthetic prescription estrogen) combined w/ medroxyprogesterone acetate (MPA). Increased risk of developing probable dementia reported in postmenopausal women ≥65 yrs of age treated w/ daily CEs combined w/ MPA. Increased risk of invasive breast cancer reported w/ estrogen plus progestin. Should be prescribed at the lowest effective dose and for the shortest duration consistent w/ treatment goals and risks.

Contraindications of Medroxyprogesterone

Further contraindications about medroxyprogesterone from pdr.net ( I think the old Physicians Desk Reference):

Undiagnosed abnormal genital bleeding, known/suspected/history of breast cancer, known/suspected estrogen- or progesterone-dependent neoplasia, active/history of DVT/PE (deep venous thrombosis, pulmonary embolism (leg blood clot, lung blood clot)) or arterial thromboembolic disease (eg, stroke, heart attack), known liver impairment or disease, known/suspected pregnancy.

Warnings of Medroxyprogesterone

Further Warnings about medroxyprogesterone from pdr.net

D/C (discontinue) estrogen plus progestin therapy immediately if PE, DVT, stroke, or MI occurs or is suspected. If feasible, d/c estrogen plus progestin therapy at least 4-6 weeks before surgery of the type associated w/ an increased risk of thromboembolism (blood clot), or during periods of prolonged immobilization. Increased risk of endometrial cancer reported w/ use of unopposed estrogen therapy in women w/ a uterus; adding a progestin to estrogen therapy has been shown to reduce risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Estrogen plus progestin therapy may increase risk of ovarian cancer. D/C estrogen plus progestin therapy pending exam if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine; d/c permanently if exam reveals papilledema or retinal vascular lesions. In cases of unexpected abnormal vaginal bleeding, perform adequate diagnostic measures. Monitor BP (blood pressure) at regular intervals w/ estrogen plus progestin therapy. Estrogen plus progestin therapy may increase plasma TGs (triglycerides), leading to pancreatitis in women w/ preexisting hypertriglyceridemia; consider discontinuation of treatment if pancreatitis occurs. Caution w/ history of cholestatic jaundice associated w/ past estrogen use or w/ pregnancy; d/c in case of recurrence. May cause fluid retention; caution in cardiac or renal impairment. Caution in women w/ hypoparathyroidism as estrogen-induced hypocalcemia may occur. Estrogen plus progestin therapy may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas. Withdrawal bleeding may occur w/in 3-7 days after discontinuing therapy. May affect LFTs and certain endocrine and blood components in lab tests.

Adverse Reactions of Medroxyprogesterone

Further Adverse reactions about medroxyprogesterone from pdr.net:

Abnormal uterine bleeding, breast tenderness, galactorrhea, urticaria, pruritus, edema, rash, menstrual changes, change in weight, mental depression, insomnia, somnolence, dizziness, headache, nausea.

Drug interactions about about medroxyprogesterone from pdr.net:

Women on thyroid replacement therapy may require higher doses of thyroid hormone.

Side Effects of Crinone (Natural Progesterone Gel) from pdr.net

For balance, I have included the information on adverse reactions on Crinone a prescription Natural Progesterone Gel.  Many of these warnings may be there because of legal liability.  For a full contrast between Progestins and Natural Progesterone, I would refer you to John Lee, MD’s books on Progesterone.  His insights are more accurate.  I have not included those here because of FTC scrutiny.

Contraindications for Natural Progesterone Crinone from pdr.net:

Undiagnosed vaginal bleeding, liver dysfunction or disease, known/suspected malignancy of breast or genital organs, missed abortion, active thrombophlebitis or thromboembolic disorders, history of hormone-associated thrombophlebitis or thromboembolic disorders.

Warnings and precautions about Natural Progesterone Crinone from pdr.net:

A dosage increase from 4% gel can only be accomplished by using the 8% gel; increasing the volume of gel administered does not increase the amount of progesterone absorbed. D/C immediately if signs of thrombotic disorders (eg, thrombophlebitis, cerebrovascular disorders, pulmonary embolism, retinal thrombosis) occur or are suspected. Include special reference to breast and pelvic organs as well as Papanicolaou smear in pretreatment exam. Consider nonfunctional causes in cases of breakthrough bleeding. Adequate diagnostic measures should be taken in cases of undiagnosed vaginal bleeding. May cause fluid retention; carefully observe patients with epilepsy, migraine, asthma, or cardiac/renal dysfunction. Pathologist should be advised of progesterone therapy when relevant specimens are submitted. Caution with history of psychic depression; d/c if depression recurs to a serious degree. May decrease glucose tolerance; carefully observe diabetic patients while on therapy.

Adverse Reactions from Natural Progesterone Crinone from pdr.net

Adverse reactions about Natural Progesterone Crinone from pdr.net.  Again these adverse reactions are due to the interaction of progesterone with strong xenoestrogens.  Many times elimination of xenoestrogens helps to avoid these adverse reactions:

Bloating, abdominal pain/cramps, breast pain, depression, headache, nausea, perineal pain, constipation, diarrhea, arthralgia, libido decreased, nervousness, somnolence, breast enlargement, nocturia.

Again, I would refer you to "What Your Doctor May Not Tell You About Menopause" by John Lee, MD for a more accurate assessment of the risks and contraindications of Natural Progesterone.  Many of the adverse effects above about Natural Progesterone may be there for legal liability reasons.