General Description

Vitex agnus castus, also known as chaste tree, is a shrub with finger-shaped leaves and slender violet flowers. It grows in creek beds and on river banks in valleys and lower foothills in the Mediterranean and Central Asia. The plant blooms in high summer and, after pollination, develops dark-brown to black fruit the size of peppercorns. The fruit possesses a pepper-like aroma and flavor. The ripe, dried fruit of V. agnus castus is the part of the plant used in medicinal preparations today.¹

Chemical Composition

The fruit of Vitex contains essential oils, iridoid glycosides, and flavonoids.² The essential oils include limonene, 1,8-cineole, and sabinene.³ The primary flavonoids are castican, orientin, and isovitexin. The two isolated iridoid glycosides are agnuside and aucubin (Figures 138-1 and 138-2).⁴ Agnuside serves as a reference material for quality control in the manufacture of Vitex extracts, although the flavonoid casticin appears to be the most active component.

FIGURE 138-1 Aucubin.

FIGURE 138-2 Agnuside.

History and Folk Use

The genus name Vitex is derived from the word vitilium, which means “plaiting.” The flexible but tough and hard branches were used to construct fences. Plinius, in the first century AD, made the earliest reference to the plant as Vitex. The species name agnus castus originates from the Latin castitas (“chastity”) and the equating of the Greek agnos with the Latin agnus (“lamb”).

The English name for V. agnus castus, “chaste tree,” is derived from the belief that the plant would suppress libido in women who took it. In Greek cities, festivals in the honor of Demeter included a vow of chastity by the local women. The Roman Catholic Church in Europe developed a variation on this theme by placing the blossoms of the plant in the clothing of novice monks to supposedly suppress libido. Interestingly, another common name for V. agnus castus, “monk’s pepper,” derived from the fact that monks in southern Europe commonly used the fruit as a spice in their cooking.

Pharmacology

Vitex acts on the hypothalamic-pituitary axis. One observed effect is that it increases the production of luteinizing hormone (LH) (Figure 138-3), resulting in a corpus luteum–like hormonal effect that shifts the estrogen/progesterone ratio in favor of progesterone.⁵ The ability of Vitex to increase or modulate the body’s progesterone levels is therefore an indirect effect and not a direct hormonal action.⁶

FIGURE 138-3 Effect of Vitex on pituitary hormone secretion.

Vitex also modulates the secretion of prolactin from the pituitary gland. In studies with rats, it was shown to inhibit prolactin release by the pituitary gland, particularly in conditions of stress. The mechanism of action appears to involve the ability of Vitex to directly bind dopamine receptors and subsequently inhibit prolactin release in the pituitary.^7,⁸ The flavonoid casticin appears to be responsible for this antihyperprolactinemia effect.⁹ Vitex also possesses significant antioxidant effect.^10,¹¹

Clinical Applications

The causes of menstrual disorders are multifaceted and can vary greatly in their manifestations. Frequently, therapeutic interventions must be used on a trial-and-error basis over a number of menstrual cycles to determine their efficacy. Nutritional interventions like vitamin B₆, magnesium, and vitamin E, as well as evening primrose oil for cyclic mastalgia, have all shown greater efficacy when used over several months. This characteristic reflects the gradual balancing effect that many of these interventions have on the female hormonal system. Vitex certainly fits this mold.

The majority of earlier clinical studies completed with Vitex were uncontrolled studies with large populations of female patients in European gynecology practices. Vitex, which has a Commission E Monograph in Germany, is commonly used in these practices as an initial intervention in a number of menstrual disorders, as follows:

• Premenstrual syndrome

• Secondary amenorrhea

Many of these conditions have been linked to corpus luteum insufficiency.

Corpus Luteum Insufficiency

Corpus luteum insufficiency (also referred to as luteal phase defect) is a manifestation of suboptimal ovarian function. In laboratory terms, corpus luteum insufficiency is usually defined as an abnormally low progesterone level 3 weeks after the onset of menstruation (serum progesterone below 10 to 12 ng/mL). This state is normal during puberty and at menopause; however, it is usually considered abnormal in women between the ages of 20 and 40 years.¹²

Corpus luteum insufficiency points to abnormal formation of ovarian follicles, an abnormality that may be so pronounced that no secondary or tertiary follicles are produced, with a resulting lack of ovulation (anovulation). Corpus luteum insufficiency also leads to a relative deficiency of progesterone. Insufficient levels of progesterone may also result in the formation of ovarian cysts.

Corpus luteum insufficiency may give rise to a myriad of menstrual abnormalities. Table 138-1 lists the most common clinical conditions in 1592 women diagnosed with corpus luteum insufficiency. Foremost are hypermenorrhea (heavy periods), polymenorrhea (abnormally frequent periods), and persistent anovulatory bleeding. Secondary amenorrhea (lack of a period) may sometimes be observed in women with corpus luteum insufficiency.

TABLE 138-1 The Most Common Clinical Conditions in 1592 Women Diagnosed with Corpus Luteum Insufficiency

DIAGNOSIS	NO. OF PATIENTS	PERCENTAGE OF TOTAL
Hypermenorrhea	418	26.3
Polymenorrhea	369	23.2
Persistent anovulatory bleeding	216	13.6
Secondary amenorrhea	202	12.7
Dysmenorrhea	186	11.7
Anovulatory cycles	175	11.0
Involuntary sterility	145	9.1
Oligomenorrhea	69	4.3
Menorrhagia/metrorrhagia	66	4.1
Irregular menstrual cycles	32	2.0
Primary amenorrhea	1	0.1