A Textbook of Clinical Pharmacology and Therapeutics

●Female reproductive endocrinology 307 ●Male reproductive endocrinology 313

CHAPTER 41

REPRODUCTIVE

ENDOCRINOLOGY

CONTRIBUTION BY DR DIPTI AMIN

FEMALE REPRODUCTIVE ENDOCRINOLOGY

INTRODUCTION

Appropriate sexual development at puberty and the cyclical
processes of ovulation and menstruation involve a complex
interaction of endocrine and target organs. Gonadotrophin-
releasing hormones (GnRH) regulate the release of the gona-
dotrophins luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) from the anterior pituitary gland. LH and FSH
promote maturation of ova and secretion of oestrogen and
progesterone from the ovaries.
Oestrogen and progesterone are derived from cholesterol.
They stimulate the breast, uterus and vagina and exert both
negative and positive feedback on the central nervous system
(CNS)–hypothalamic–pituitary unit resulting in inhibition
and stimulation of gonadotrophin secretion.
The main hormones secreted by the ovary are oestradiol-
17 β, oestrone, progesterone and androgens. Oestrogens influ-
ence the development of secondary sexual characteristics,
including breast development and the female distribution of
fat, as well as ovulation during the reproductive years.
From the start of menses until the menopause, the primary
oestrogen is oestradiol-17β, whereas in post-menopausal women
oestrone predominates. Oestriol is only present in significant
amounts during pregnancy and is made by the placenta which
converts dehydroisoepiandrosterone (DHEA) from the adre-
nal cortex of the fetus to oestriol.

OESTROGENS

Properties

The properties of oestrogens include the following:

• stimulation of endometrial growth;


• maintenance of blood vessels and skin;


• reduction of bone resorption and increase of bone formation;


• increase uterine growth;


• increase the hepatic production of binding proteins;


• increase circulating clotting factors II, VII, IX, X and
  plasminogen;
  
  
  • increase high-density lipoprotein (HDL);
  
  
  • increase biliary cholesterol;
  
  
  • control salt and water retention.
  
  
  
  

Uses

Oestrogens are used in:

• oral contraception;


• the treatment of symptoms of menopause;


• the prevention of osteoporosis. Fractures of the spine,
  wrist and hips are reduced by 50–70% and there is
  about a 5% increase in spinal bone density in those
  women treated with oestrogen within three years of the
  onset of menopause and for five to ten years thereafter.


• the treatment of vaginal atrophy;


• the treatment of hypo-oestrogenism (as a result of hypo-
  gonadism, castration or primary ovarian failure);


• treatment of primary amenorrhoea;


• treatment of dysmenorrhoea;


• treatment of oligomenorrhoea;


• treatment of certain neoplastic diseases;


• treatment of hereditary haemorrhagic telangiectasia
  (Osler–Weber–Rendu syndrome);


• palliative treatment of prostate cancer.
  Ethinylestradiol, a synthetic oestrogen, is an alternative for
  many of the above indications.
  Oestrogens are no longer used to suppress lactation because
  of the risk of thromboembolism. Bromocriptineis used instead.

Key points

Main uses of oestrogen

• oral contraception;


• replacement therapy.

Adverse effects

Common symptoms include nausea and vomiting, abdominal

cramps and bloating, breast enlargement and tenderness, pre-

menstrual symptoms, sodium and fluid retention. Salt and

water retention with oedema, hypertension and exacerbation

of heart failure can occur with pharmacological doses. In men,