Biology of Disease

The plasma concentration of estradiol is low before puberty but increases

rapidly and fluctuates during the menstrual cycle, a series of cyclical changes

in the ovary, uterus and pituitary that occur approximately every 28 days until

the menopause. Variations in plasma hormones in the menstrual cycle (Figure

7.40) depend on interactions between the hypothalamus, anterior pituitary

and ovaries. Follicle stimulating hormone is released at the beginning of the

cycle and increases growth of the follicles in the ovaries. Estradiol production

increases the sensitivity of the pituitary to GnRH but decreases its secretion

by the hypothalamus. The release of estradiol gradually increases and a follicle

matures during the first half of the cycle. At the start of each cycle, about 20

secondary follicles enlarge and begin to secrete estrogen and the hormone

inhibin, and a cavity filled with follicular fluid forms around their ova. This is

referred to as antrum formation. By about the sixth day, one of the secondary

follicles in an ovary has outgrown the others and becomes the dominant

follicle. Its secretion of estrogen and inhibin decreases the secretion of FSH

X]VeiZg,/ DISORDERS OF THE ENDOCRINE SYSTEM

&.' W^dad\nd[Y^hZVhZ

Figure 7.38 Molecular models of (A) the active

form of testosterone and (B) estradiol shown in

red bound to SHBG. PDB files 1KDM and 1LHU

respectively.

Oral contraceptives (Figure 7.39) known colloquially as the pill,

contain a synthetic version of estrogen, called ethinylestradiol

and the synthetic version of progesterone, progestogen. The

estrogen prevents ovulation taking place, whereas progestogen

acts on the pituitary gland to block the normal physiological

control of the menstrual cycle. Progestogen alters the lining of

the uterus so that it is unsuitable for implantation and increases

the viscosity of the mucus in the cervix, so that conception is less

likely even if ovulation does occur. Oral contraceptive pills are

taken daily for three weeks and then stopped for a week during

menstruation.

Pincus (1903–1967) began development of the contraceptive

pill in 1950. Within a few years, clinical trials on 6000 women

began in Puerto Rico and Haiti. The first commercially available

contraceptive pill was introduced in 1960 after it was discovered

that Mexican yam (Pachyrhizus erosus) was a cheap natural source

of the hormone precursors required to make the pill. Over 60

million women worldwide use the pill with about three million in

the UK. Early contraceptive pills contained between 100–175 Mg

of estrogen and 100 mg of progestogen. However, shortly after

introduction of the pill, some concern was expressed about their

side effects. These included an increased disposition to blood

clots, heart attacks and strokes, although the risks involved were

still relatively small. Studies by 1969 showed that the increased

BOX 7.3 Oral contraceptive pill

Figure 7.39 Examples of some types of oral

contraceptive pills. The inset shows a packet

of morning after pills. Courtesy of the Young

Person’s Sexual Health Clinic, Brook Advisory Center,

Manchester, UK.