Gynecological disorders

These include a variety of conditions, such as menopausal symptoms, premenstrual syndrome including mastodynia, and dysmenorrhea. All are directly or indirectly related to imbalances or deficiencies in the production of female sex hormones or prostaglandins.

In the female menopause—the period following the complete cessa- tion of menstruation—estrogen production drops to about 10 percent of its premenopausal levels and progesterone production drops to nearly zero. This results in various symptoms, four of which are more or less common: (1) vasomotor disorders (hot flashes), (2) urogenital atrophy, (3) osteoporosis, and (4) psychological disturbances. Administration of con- jugated equine estrogens has been a common treatment for menopausal

symptoms. 12 However, hormone replacement therapy (HRT) has been associated with a slight but significant increase in the risk of developing breast and endometrial cancer, 13 leading to marked increase in the use of herbal remedies as alternative therapy. 14 Premenstrual syndrome (PMS) is characterized by certain emo- tional and physical symptoms as well as behavioral changes that occur during the premenstrual (luteal) phase of the menstrual cycle and then disappear several days after the onset of menstruation. Its etiology is unknown; however, premenstrual symptoms are closely linked to the rise and fall of gonadotropin and ovarian hormones, neurotransmit- ters, and prostaglandins during the menstrual cycle. Some studies suggest that normal fluctuations in estrogen and progesterone trigger the symptoms by an unknown mechanism. The beginning of premen-

strual symptoms parallels the postovulatory rise in progesterone levels, but the highest severity of symptoms occurs five to six days after the peak of progesterone levels. When estradiol levels peak during the preovulatory phase, women feel better and have minimal symptoms. The rate of decline in progesterone and estradiol during the late luteal phase has been proposed as being more important in causing symptoms than absolute basal values. Stress may play a significant role, and some women appear to be predisposed to PMS by various genetic, biological, or psychological factors. 15

156 Tyler's herbs of choice: The therapeutic use of phytomedicinals Primary dysmenorrhea—that is, painful menstruation in the absence

of pelvic pathology—occurs with considerable frequency, particularly among adolescent females. Pain usually begins with, or just slightly before, the onset of menstrual flow and lasts for periods of up to two days, seldom longer.

It has now been shown that this condition is associated with an increased production and concentration of prostaglandin in the endome- trium during the luteal and menstrual phases of the cycle. This results in hypercontractility of uterine muscle during dysmenorrhea. Prostaglandin inhibitors have proven to be very effective in relieving the associated symptoms. 15

The existence of naturally occurring steroidal estrogens in species other than vertebrates is uncertain; however, it is estimated that more than three hundred plants possess compounds with estrogenic activity.

A few of these phytoestrogenic herbs have utility in treating health problems associated with gynecological disorders.

Herbal remedies for gynecological disorders Black cohosh

The dried rhizome and roots of Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt.), family Ranunculaceae, is sometimes referred to as black

snakeroot or cimicifuga. It has an ancient reputation as a remedy for the treatment of “female complaints,” a generic term that probably includes all of the gynecological disorders just discussed. As such, it was one of the ingredients in the famous proprietary medicine, Lydia E. Pinkham’s Vegetable Compound. 16

Hänsel has reviewed the literature supporting claims of estrogen-like activity for extracts of black cohosh. 17 A clinical study of hysterectomized patients with climacteric symptoms by Lehmann-Willenbrock and Riedel showed no significant differences among groups treated with various

estrogens and those receiving black cohosh extracts. 18 The beneficial effects were slow to appear, requiring up to four weeks to reach a maximum. More recently, investigators have shown that an alcoholic extract of black cohosh suppressed hot flashes in menopausal women by reducing the secretion of luteinizing hormone (LH). It also suppressed LH production in ovariectomized rats. Synergistically acting compounds are thought

to be responsible for this effect, but they remain unidentified. 19 The drug does contain the isoflavone formononetin, which may be the basis of the estrogenic activity because it is converted in vivo by the gastrointestinal microbial flora to compounds that bind to the estrogen receptor—first to daidzein and then to the more active isoflavan equol. In addition, the steroidal triterpene glycosides actein, 27-deoxyactein, and cimicifugoside

Chapter eight: Endocrine and metabolic problems 157 have been identified, but their role in the gynecological activity of black

cohosh is unknown. 20 German Commission E has found black cohosh to be effective for the treatment of PMS and dysmenorrhea, as well as for nervous conditions associated with menopause. 21 The herb is normally administered in the form of a 40–60 percent alcoholic extract in a quantity equivalent to 40 mg of drug daily. A decoction prepared from 0.3–2.0 g of the herb may also be employed. Administration of the drug sometimes causes stomach upsets; otherwise, no problems or contraindications have been reported. In view of the fact that no long-term toxicity studies on the use of black cohosh have been carried out, administration of the herb should be limited to a period of no longer than six months.

Chasteberry The aromatic fruit of Vitex agnus-castus L., a small deciduous tree or large shrub of the family Verbenaceae that grows in the Mediterranean region, has long been used in European herbal medicine, but it is little known in the United States. In recent years, however, an extract of the fruit has become available in that country. 22

Chasteberry is now believed to have dopaminergic properties. Dopamine and dopamine agonists inhibit the secretion of the peptide hormone prolactin by the pituitary gland. 15,23 Exactly what effect this has on PMS, dysmenorrhea, and menopause is not entirely clear, but the symptoms of PMS, including mastodynia as well as amenorrhea and irregu- lar menses, have been associated with elevated blood levels of prolactin. Drugs that reduce prolactin concentrations usually restore the menstrual cycle to normal. 15

The therapeutic benefit of a single daily dose of a 20-mg commercial aqueous-ethanolic extract of vitex fruits was investigated in a random- ized, double-blind, placebo-controlled trial. Fifty-two women with disturbances of the menstrual cycle were chosen for the study. Following a three-month treatment period, women receiving vitex extract had a significant reduction in prolactin release in response to tropic hormone stim- ulation compared to placebo. In addition, women in the vitex group had a significant reduction in PMS symptoms, while the placebo group did not.

No side effects were reported. 24 The nature of the chemical principles in chasteberry responsible for this prolactin-depressant effect has not been established. Preliminary isolation studies utilizing vitex extracts containing water-soluble substances, pressure filtration through molecular sieves, and column chromatography have led to the identification of at least three different dopaminergic compounds that potently inhibit prolactin release from cultured rat pituitary cells. 25

The German Commission E has recommended the use of chasteberry for a variety of menstrual disturbances and mastodynia. 26 The herb is

158 Tyler's herbs of choice: The therapeutic use of phytomedicinals usually administered in the form of a concentrated alcoholic extract of

the fruit; average dose is 20 mg per day. Patients are warned that the herb should not be used during pregnancy or lactation, and the use of the herb does occasionally produce an itchy rash in sensitive consumers.

Evening primrose oil The small seeds of this native American wildflower, Oenothera biennis L. (family Onagraceae) contain about 14 percent of a fixed oil of which

70 percent is cis-linoleic acid and 9 percent is cis-gamma-linolenic acid (GLA). The latter constituent is a relatively uncommon one that is found in quantity in only a few other plants, such as black currant and borage seeds. 27–29

Theoretically, GLA can be converted directly to the prostaglandin pre- cursor dihomo-GLA (DGLA). Therefore, administration of the oil containing it might be beneficial to persons unable to metabolize cis-linolenic acid to GLA and to produce subsequent intermediates of considerable metabolic

significance, including the less inflammatory PGE 1 , which can lead to an imbalance in the ratio of inflammatory to noninflammatory prostaglandin compounds. 30 Illnesses thought by some to arise from such metabolic deficiencies and imbalances—and therefore presumably treatable by the administration of evening primrose oil—are numerous. The more significant ones in terms of supporting evidence are PMS and associated mastodynia, as well as atopic eczema. However, even in these conditions, which have been the subject of a number of studies, the results are controversial.

A comprehensive literature review 31 has reported that evening primrose oil had some utility in treating PMS and mastodynia. In the latter case, the rationale was that low levels of PGE 1 may increase the effect of prolactin on breast tissue, causing mastodynia. On the other hand, a recent report describing a literature search of clinical trials of evening primrose oil for the treatment of PMS with a view to performing a meta- analysis found only five trials where randomization was clearly indicated. Inconsistent scoring and response criteria made a meta-analysis inappro- priate. The two best-controlled studies failed to show any beneficial effects for evening primrose oil in the management of PMS. 32

Clinical trials testing the effects of the oil in the treatment of atopic eczema have also provided conflicting results. 31 In view of these uncertainties regarding the efficacy of evening primrose oil and the relatively high cost of the 500-mg capsules (ca. $0.25 each—minimum dose of four per day), one cannot unreservedly recom- mend the use of this product. This position is further supported by the lack of toxicity data regarding its long-term use.

GLA-rich seed oils from two other plant sources—black currant oil and borage seed oil—are currently available in the United States.

Chapter eight: Endocrine and metabolic problems 159 Black currant oil

Seeds of Ribes nigrum L.( family Grossulariaceae), the European black currant, yield a fixed oil containing 14–19 percent GLA. Capsules containing approximately 200 or 400 mg of the product are currently marketed.

Gynecological disorders