Investigation of the pharmacokinetics and pharmacodynamics of progestogen-only contraceptive implants and factors controlling menstruation

Li, Xiao Feng (1994). Investigation of the pharmacokinetics and pharmacodynamics of progestogen-only contraceptive implants and factors controlling menstruation. University of Birmingham. Ph.D.

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Abstract

This pharmacokinetic and pharmacodynamic study has confirmed that the single subdermal rod Implanon, releasing 3-ketodesogestrel, provides long-term contraception for at least 3 years. Its contraceptive effectiveness is achieved by inhibition of pituitary function and ovulation as well as the induction of cervical mucus blockage. Luteal activities and progesterone levels were well below ovulatory levels. Fertility recovery was rapid with a return of ovulation by 8 weeks following implant removal. The major side effect of Implanon was menstrual irregularities.

Increasing evidence suggests that the mechanism controlling menstruation and its disorders are regulated by local factors within the endometrium itself. The commencement of menstruation is characterised by intense vasoconstriction of the spiral arterioles. This study examined the distribution and localisation of a potent vasoconstrictor, angiotensin II and its receptor subtypes in the endometrium using immunocytochemistry and quantitative receptor autoradiography. Angiotensin II-like immunoreactivity showed cyclic variations throughout the menstrual cycle. In the early proliferative phase a higher level of immunoreactivity was detected in the stroma and glandular epithelia whereas in the late secretory phase the maximal levels of immunoreactivity was localised around the blood vessels. In the progestogen-treated endometrium, increased angiotensin II-like immunoreactivity was noted in the endometrial stroma and glands. The human endometrium contains predominantly AT\(_2\) receptor subtype with a relatively low level of AT\(_1\) receptors. The AT\(_2\) receptor level showed cyclical changes, increasing from the early to mid proliferative phase, to a maximal level in the early secretory phase. The concentrations of AT\(_2\) receptor subtypes were significantly reduced in the progestogen treated endometrium.

The present study suggests that a local renin-angiotensin system is present in the human endometrium which may play an important role in the control of menstruation and irregular endometrial bleeding caused by progestogen only contraceptives.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):