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Kacip fatimah raises libido by increasing testosterone levels in women

Version 1.0, August 2004:, Jefferson Griuen

The following is a summary on kacip fatima's effect on hormone levels in human, primarily females. It was prepared by the Malaysian Herbal Medicine Research Centre. Interestingly, studies have shown that kacip fatima increases the levels of free testosterone, not estrogens. Take note that female libido is clearly influenced by small amounts of free testosterone.

"Binding to estrogen receptors are being investigated. If they were phytoestrogens, the extract should also displace estradiol binding to the estrogen receptors. These phytoestrogens will then have certain effects on the animals depending on whether they are full estrogen agonists, or antagonists, or partial agonists like clomiphene. It is also possible that KF acts as estrogen receptor modulators (SERMS) like Tamoxifen or Raloxifene which is active at certain tissues only (4,5). For example, Reloxifene being active only at the bones and lipids and not the breasts and uterus, common target tissues for estrogen action.

"On the other hand, a lot more is known about estrogen receptors and how it causes effects at the cellular level. There are two isoforms, alpha ( ERa) and beta (ERb) with 97% homology at the DNA binding site and 59% homology at the ligand binding site and more diverse at the or regions of the receptor molecule. Both isomers bind estradiol effectively and combine together or dimerized upon binding to estradiol at the DNA binding site called the estrogen response element ERE. The two isomers differ most at the so called Activation Function 1 and Activation Function 2 ( AF1 and AF2 ) in the N- and C- terminus respectively. When E2 binds to the receptor binding domain, the AF2 is exposed and interacts with cofactors which helps transmit the signal to the DNA (5,6,7). Other mechanism of action also exists in the tissues. Rather than dimerize, the ER may actually bind to DNA bound protein complexes such as Activating protein-1 and causes transrepression.

"The gene expressions are controlled by the AP-1 sits. The SERMS raloxifene and Tamoxifen for example stimulate the AP-1 with ERa or ERb, whilst E2 stimulate the tyranscription only in presence of ERa. If ERb is present then the AP-1 regulated transcription is repressed (8). The E2 signalling action may also be modified by other signal transducing systems, independent of the ligand itself. Example, epidermal growth factor may cause phosphorylation of the serine residues of the estrogen receptor at the AF-1 region and increase the transcription activity of the E2 ER binding (9). The action of estrogens may also be modified by enzymes which may convert the active E2 to inactive Estriol or Estrone similar to the enzyme 11- hydroxysteroid dehydrogenase in the tissues which convert active cortisol to inactive cortisone (10,11).

"In theory therefore, the phytoestrogen may have effects at the site of binding at both or one or other of the Estrogen receptor isomers, or act as an AF or as an activating Protein or like EGF act by modulating the receptor molecule, or as a peripheral enzyme modulator such as 11HSD. Recent studies at the IMR gave some clues to its mode of action. Given to normal female rats, the serum level of estradiol E2 were unchanged but the level of free testosterone wee significantly higher. In castrated rats, there were no significant effects on the levels of E2 or testosterone. These preliminary data suggest that Kacip Fatimah does not increase estrogen levels and but instead causes increase free testosterone from the ovaries a it does not work without ovaries. The increase in free testosterone may cause increase in libido and sexuality in women. This could be the effect that the women taking Kacip Fatimah are looking for!! It also means the Herb should not work in menopausal women if the effect is via increase production of testosterone ifrom the ovaries. On the other hand, if it were to work by peripheral enzymes converting E2 to testosterone, then it is independent of the ovaries but still needs adequate levels of estradiol. In women without pituitaries therefore, the herb should not work, unless the effect is like Clomiphene and causes increase in secretion of FSH from the pituitary, or by antagonizing the hormone, Inhibin produced by the ovaries at the pituitary level.

"Clearly the potential effect of Kacip Fatimah as a SERM and any possible increase risk for breast or uterine cancer has to be considered. The following pharmacological studies, in-vitro and in-vivo are being proposed to determine the possible mechanism of actions of KF, and the Clinical trials (Phase I, II, III) would evaluate the physiological effects of Kacip Fatimah in women and support the basic research being carried out in the IMR....

"Two studies have shown that the plant exhibit oestrogenic properties. Jamal et al. (1999)2 in vitro study using human endometrial adenocarcinoma cells of the Ishikawa-Var I line showed that the ethanolic extracts of the roots of Labisia pumila var alata exhibited a weak but specific estrogenic effect on the cells, resulting in enhanced secretion of alkaline phosphatase. Husniza et al. (2000)3 shows the water extracts of the Kacip Fatimah were able to displace estradiol binding to antibodies raised against estradiol, making it similar to other estrogens such as estrone and estradiol.