The reproductive tract

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Chapter 20 The reproductive tract

Drugs used in hormonal disorders have been covered in Chapter 19. Other drugs that are used in obstetrics, including substances used in childbirth, and genitourinary disorders and erectile dysfunction in men, will be mentioned briefly here.

Phytomedicines in childbirth

Taking (any) medicine during pregnancy is generally not advisable as safety of the mother and fetus cannot be guaranteed. Raspberry leaf is included here simply because according to folklore it has a widespread use in facilitating childbirth, and it is often recommended that it be taken during pregnancy for this purpose, but the use cannot be recommended as there is little clinical evidence available to demonstrate either safety or efficacy.

Ergometrine

Ergometrine (Fig. 20.1) is an alkaloid extracted from ergot (Claviceps purpurea Tul.), a parasitic fungus growing on cereals, usually rye. It is used to manage the third stage of labour (in conjunction with oxytocin), and to control postpartum haemorrhage if the placenta has not been completely expelled. It must be used only under the care of a midwife or obstetrician.

Fig. 20.1

Raspberry leaf, Rubus idaeus L. (Rubi idaei folium)

Raspberry leaf (Rubus idaeus, Rosaceae) ‘tea’ has been used for centuries to facilitate childbirth, and it is usually recommended that it be drunk freely before and during confinement for maximum benefit. The raspberry shrub is well known and will not be described. It is cultivated in many temperate countries for the fruit.

Constituents

The leaves have not been well investigated, but contain uncharacterized polypeptides and flavonoids, mainly glycosides of kaempferol and quercetin, including rutin.

Therapeutic uses and available evidence

A retrospective observational study on 108 mothers in Australia indicated that a shortening of labour and reduction in medical intervention occurred, with no untoward effects apart from a single case of diarrhoea and anecdotal reports of strong Braxton Hicks contractions. However, a larger, randomized placebo-controlled trial of 192 women by the same authors did not confirm such benefits, although no adverse effects for either mother or baby were noted (Simpson et al 2001). Uterine relaxant effects have been demonstrated in animals (Rojas-Vera et al 2002), and raspberry leaf appears to affect only the pregnant uterus of both rats and humans, with no activity on the non-pregnant uterus. However, no further identification of the active principle(s) has been made and a recent review concludes that in the absence of good clinical data, raspberry leaf cannot be recommended in pregnancy (Holst et al 2009).

Male sexual dysfunction (impotence)

Male impotence (failure to produce a satisfactory or sustainable erection) may result from psychogenic, vascular, neurogenic or endocrine abnormalities (such as diabetes), or drug treatment (e.g. with antihypertensives and antidepressants). It can be treated with either intracavernosal injections of papaverine or alprostadil (prostaglandin E1), intraurethral application (alprostadil) or systemically [sildenafil (Viagra) or apomorphine]. Medical assessment is needed before these drugs are prescribed. Although papaverine is of natural origin, it is only suitable for self-medication after medical diagnosis, but there are several herbal products available, which claim to treat this distressing disorder. The most common are probably epimedium, and yohimbe, a traditional aphrodisiac, and there are others, which are often strange botanical mixtures and usually sold under the description ‘Herbal Viagra’. There is no good clinical evidence of efficacy for any of these, although epimedium has some pharmacological actions in common with those of sildenafil (Viagra^®), and may have a placebo effect.

Epimedium brevicornum Maxim (Epimedii herba) and Epimedium spp.

Epimedium brevicornum Maxim (Berberidaceae) and related species are also known as ‘horny goat weed’. The herb was apparently discovered by the Chinese, who noticed that when goats had eaten it, they were eager to mate, and for this reason they called the herb ‘yin yang huo’, or ‘licentious goat plant’. Epimediums are sprawling, attractive, perennial herbs, with cordate leaves and white, cream, pink, yellow or lavender flowers. Although native to Asia and the Mediterranean region, they are widely cultivated. Epimedium has been used for the treatment of erectile dysfunction in Traditional Chinese Medicine for many years. It is also used to ease menopausal symptoms in women and to treat and prevent osteoporosis.

Constituents

The flavonoids are the active constituents, the most important being icariin and its analogues, with epimedin A, B, and C, and baohuoside I.

Therapeutic uses and available evidence

Icariin has phosphodiesterase type 5 inhibiting effects (the mechanism of action of sildenafil) and may also have neurotrophic effects (Zeng et al 2010, Ma et al 2011). A study of the effects of icariin administered daily to cavernous nerve-injured rats found that the ratio of intracavernous pressure to arterial pressure was significantly higher compared with control (and also single-dose icariin-treated) animals. The penile tissue of rats treated with icariin showed greater positivity for neuronal nitric oxide synthase and calponin, and cultured pelvic ganglia treated with icariin had significantly greater neurite length (Shindel et al 2010). Icariin is also a bone anabolic agent that may exert its osteogenic effects through the induction of bone morphogenetic protein-2 and NO synthesis, subsequently regulating gene expression and contributing to the induction of osteoblast proliferation and differentiation (Hseih et al 2010).

Papaverine

Papaverine (Fig. 20.2) is an alkaloid extracted from the opium poppy (Papaver somniferum L.). It is most often used for the treatment of impotence of neurological or psychogenic origin. As it must be given by intracavernosal injection, it is normally only used as a last resort when less invasive treatments have failed.