Black cohosh may reduce side effects of Clomid / clomiphene

Clomid is one of the most commonly used pharmaceuticals in the treatment of fertility concerns today.  It is often the first therapy used.  Clomid (also known as clomiphene) binds to estrogen receptors, inhibiting the action of estrogen (which is produced by developing follicles) on the hypothalamus in the brain.   As a result, the pituitary gland perceives estrogen levels to be low (when they actually are not), and it responds by producing increased levels of both LH and FSH.  This causes increased follicle production by the ovaries, and stimulation of ovulation.pregnancy with clomid therapy

As effective as this therapy can be at inducing ovulation, studies have indicated fertility specific side effects of clomiphene, many of which are caused by its antagonism to estrogen. The major fertility related side effects are: 1) thinning of the endometrial lining and 2) reduction of cervical mucous required for entry of sperm into the uterus.

One of the isomer forms of clomiphene has a slow excretion rate from the body (it can take more than 6 weeks to be excreted).  If clomiphene therapy is used for longer than two months, side effects can be more pronounced, resulting in greater thinning of the endometrial lining which is needed for healthy implantation. In women over 40, endometrial lining thins naturally, and perhaps this is why clomiphene is often not an effective treatment in this group of patients.

For many women, the ovulation induction produced by this medication can be the answer to ovulation difficulties however therapy often must be stopped after a short period due to side effects over time. Estrogen therapy has been studied in conjunction with Clomid presumably to offset the anti-estrogenic effects of the medication, with mixed results.  Some studies have found giving additional estrogen to women to be helpful, and others have found it to be of no benefit.

Recently, two studies have been completed on combining black cohosh (also known as Cimicifuga racemosa) with clomiphene in patients seeking treatment for infertility.  Cimicifuga is a botanical therapy, often used in womens health to treat menopausal conditions such as hot flashes.  Estrogenic effects of black cohosh remain highly debated, with early studies indicating that it  directly affects estrogen receptors, and more recent studies showing that the effect of the plant may occur from an entirely different mechanism.  Without yet knowing the exact mechanisms through which black cohosh works, several convincing studies have indicated it to be beneficial in the clinical treatment of hormonal disorders.  A recent study has indicated that black cohosh may reduce proliferative effects of estrogens on tissues, which is in line with the effect of many phytoestrogens, however the mechanism for this remains to be elucidated.

In the first study conducted in 2008, black cohosh was found to significantly increase estradiol and LH concentrations in patients taking clomiphene therapy.   Endometrial thickness, serum progesterone and clinical pregnancy rate in patients were significantly higher in the black cohosh group as compared to control.

The second study was completed in 2009. In this study of patients taking clomiphene, black cohosh given in the follicular phase was compared to estrogen therapy, presumably in order to determine which could reduce side effects more effectively. The black cohosh group needed significantly fewer days for healthy follicular development, had a thicker endometrial lining and had higher estradiol concentration at the time of HGG ovulation trigger when compared to the estrogen replacement therapy group.  Clinical pregnancy rate was 14.0% in the estrogen replacement group versus 21.1% in the black cohosh group. Although this did not reach clinical significance, it appears that the black cohosh group did display many benefits overall when compared to the estrogen replacement group. When results from the previous study are also considered, it appears that this therapy may warrant serious consideration and further study for those undergoing clomiphene treatment.

More studies will need to be conducted in order to determine the mechanisms of this herbal medicine’s benefits for patients undergoing modern assisted reproductive technology therapies.


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H1N1 Treatments: Anti-Inflammatory Properties of Herbal Medicines


It is now commonly accepted that many severe or fatal reactions to influenza are caused by intense inflammatory overreactions of the immune system.    A group from the Research School of Biology, Australian National University released an article on September 24, 2009 compiling evidence on this topic.

Cytokines are chemicals which are produced in immunological inflammatory reactions in the body.  Studies indicate that certain plant extracts can be protective against lethal reactions for mice which are infected with a virulent influenza strain. This occurs through inhibition of novel inflammatory cytokine High Mobility Group Box 1 protein (HMGB1) by these plant extracts.  Angelica sinensis (also known as Dang Gui) and Salvia Miltiorrhzia (also known as Dan Shen) were two of the herbal medicines studied which had this effect on HMGB1.

A drug known as gemfibrozil (a drug normally used to lower blood lipids) prevented a significant proportion of mice infected with H1N2 influenza from developing a fatal disease in a 2007 study.  Gemfibrozil has a known ability to reduce expression of inflammatory cytokines, and this is thought to be the mechanism through which it protects against severe or fatal reactions in the mice.  The action of this drug adds to the evidence that it is the body’s overproduction of cytokines which is involved in these severe cases of influenza.

Other studies have investigated Red Clover, Ginseng, Isatis, and Andrographis indicating that they modulate and reduce various aspects of cytokine response.  Forsythia, Honeysuckle, Balloon Flower root, Licorice, Camilla sinensis (green tea) and Ginger have also been researched, results of which indicate that they reduce both production of pro-inflammatory cytokines and pro- inflammatory mediators (such as reactive oxygen species and nitric oxide).  This is likely caused by suppressing a gene known as NF-kB which is often elevated in severe viral disease states, and which is related to disease conditions leading to multiple organ failure such as those in fatal influenza sepsis.

Combinations of these herbs are often used in Traditional Chinese Medicine to treat influenza from the earliest stages onward.  For this reason it is particularly interesting to determine the immunological mechanisms through which they work.

In summary, this information indicates that it is the host response of the human body which may be involved in many of the fatal reactions in viral influenza infections.  Treatments which can modulate this response in a patient who has contracted a viral influenza are therefore of great interest.  More research needs to be done on these herbs since due to their mechanisms, they may be promising therapies to integrate with conventional influenza treatments.


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