www.pharmaprodia.com - PHARMAPRODIA
  • 623-404-1000
  • Contact Us
  • Refill a prescription
  • Fax: 623-256-6491
  • M-F 0800-0500 PM Sat/Sun By appointment only

Bio-identical Progesterone (Not Synthetic; Big Difference)

Pregnenolone and Progesterone summary

Progesterone is a steroid hormone primarily produced in the ovaries. High amounts of Progesterone are produced during pregnancy. The adrenal glands and nerve cells make little quantities of progesterone as well. Progesterone is synthesized from pregnenolone, which is derived from cholesterol. Progesterone acts as a precursor to DHEA, testosterone, estrogen, cortisone. The predominant role of progesterone is to balance or counteract the effects of estrogens. Estrogen poses a great risk for breast cancer. Progesterone plays a crucial role in bone formation and prevention of osteoporosis. Some women have progesterone levels of almost zero at menopause. The placenta produces somewhat 300mg and up to 400 mg of progesterone daily in the third quarter of pregnancy and this fact alone tells us that such progesterone levels are extremely safe for the mother and baby. On the opposite side of the spectrum are so-called progestins or man-made progesterone, which show significant damage by causing birth defects even at the fraction of the dose offered by natural bio-identical hormones. The Women's Health Initiative, though very flawed in many ways showed a significantly higher risk of breast cancer, strokes, heart disease when synthetic (non-bio-identical estrogens were combined with synthetic progestins). On the contrarily, a 10-year study in France involving bioidentical hormones estradiol and progesterone was devoid of such deleterious side effects (De Lignieres et al., 2002). Progesterone as a hormonal supplement has little to no side effects especially when used following the right route of administration. 

The best and most reported side effects are sleepiness; and this explains why it is best taken at night. Progesterone when administered reduces nighttime sleep disturbances, increases growth hormone secretion, and decreases TSH levels. These effects are partly mediated by progesterone metabolites that stimulate the γ-aminobutyric acid (GABA) system through neuroactive progesterone metabolites such as Pregnenolone and allopregnanolone (Zheng, 2009), (Frye, 2007). Breast heaviness, fatigue and bloating can occur when extremely high doses of progesterone are taken over a long period of time partly due to its conversion to deoxycorticosterone, which is also called 11-Deoxycorticosterone (DOC), 21-hydroxy progesterone, the 21-hydroxy-variant of progesterone or as the 11-deoxy-variant of corticosterone. It is a steroid hormone produced by the adrenal glands, which possesses an extensive mineralocorticoid activity. The quantity of this hormone in a woman varies according to their genetic makeup. When enough progesterone is not available to complement estrogen, estrogen dominance ensures with estrogen becoming the dominant hormone. This may cause symptoms including weight gain. Breast tenderness, fibrosis breasts, poor sleep, decreased sex drive, mood swings, and depression.

 Several metabolic by-products of progesterone have been identified. These by-products put an extra and unnecessary burden on the liver in its ability to metabolize them. This happens when progesterone is taken orally in capsule form. In the gastrointestinal tract, as much as 90 per cent of an oral dose is destroyed within 15 minutes. In the past, several studies using unreliable analytical techniques have misreported on the pharmacokinetics of progesterone. Today we are reevaluating the way we dose or analyze progesterone levels especially with innovative analytical methods. When progesterone is taken orally, due to first-pass metabolism, high levels of its metabolites occur. A vast majority of previous studies have used radioimmunoassay (RIA) to measure progesterone levels. This analytical technique has some cross reactivity, which makes it unable to differentiate between progesterone and its metabolites such as allopregnanolone and Pregnenolone leading to false reporting of high progesterone levels using radioimmunoassay (RIA); thus leading to inaccurate dependent pharmacokinetic parameters (H, 2011), (Kuhl & Schneider, 2013), (Davey, 2018). 

Progress has been made in this new age of analytical techniques that has prompted comparative studies making use of reliable and exact reproducible methods such as liquid chromatography and mass spectrometry (LC–MS). Newer studies have concluded that RIA alone did overestimate levels of progesterone by up 5 to 8-fold (H, 2011), (Kuhl & Schneider, 2013), (Davey, 2018). This makes this a mandatory requirement to reliably assay oral progesterone levels which up to the present times has been flawed with inaccuracies. This inaccurate reporting often does not occur when the vaginal and injectable routes of administration are used to administer the progesterone (H, 2011), (Kuhl & Schneider, 2013), (Davey, 2018).

 Conversely, the same issues are not applicable to parenteral routes of progesterone such as vaginal administration and intramuscular injection, due to the fact that such routes of administration are not subject to first pass metabolism in the liver and thus, there are metabolites formed when such a route is used. After oral dosing, rapid deactivation in stomach occurs; and liver metabolism of the remainder progesterone which was able to get to the liver where it is further metabolized to different metabolites. As a hypothetical example, if one were to take for example 200 mg of oral progesterone, and the blood test comes back with a level of 20 nanograms per milliliter, it is safe to conclude that the true progesterone level is more likely to be only about 4 ng / ml, and the rest considered inactive metabolites with a sole role of causing side effects. This makes it impossible also for such metabolites to be identified in a saliva test. This could help also explain why progesterone given transdermally produces little to no sleepiness compared to orally administered progesterone. Thus, a measurement of bioavailable progesterone (through a saliva test) will result in levels much more accurate than blood serum (or plasma) levels. For more on Progesterone pharmacokinetics, see section on Pharmacokinetics of progesterone.