surtururudrusrur

1. ORAL CONTRACEPTION AND HORMONE
REPLACEMENT THERAPY

2. • Worldwide, many women are taking gonadal steroids (oestrogens and
progestogens) as oral contraceptives (OCs) or sex hormone
replacement therapy (HRT).
• Gonadal steroids have the potential to influence many metabolic
systems and hence biochemical variables in the blood

3. • Methods for contraception can be divided into hormonal and non-
hormonal methods.
• The latter include sterilization, barrier methods, the use of
spermicides and natural methods. These do not have metabolic
effects
• Hormonal methods involve treatment of the woman (usually) with
hormones to prevent conception, and have the potential to cause
secondary metabolic disturbances.

5. • The most widely used are combined oral preparations of oestrogen
and progestogen.
• Both components can have metabolic effects, in particular affecting
lipid and glucose metabolism.
• Older combined oral contraceptives used relatively high doses of
oestrogen, which could increase the concentration of thyroxine
binding globulin, and hence increase total T4 (but not free T4)

7. • Contraceptive progestogens are used in order to increase
contraceptive efficacy in combined regimens, on their own in the
‘mini-pill’ or to control menstrual bleeding.
• HRT progestogens are used to prevent endometrial proliferation,
hyperplasia and neoplasia.

8. Metabolic effects of oestrogens
• Oestrogens suppress the secretion of FSH by the pituitary and hence
suppress follicular maturation.
• Oestrogens tend to increase plasma triglyceride concentrations,
reduce LDL-cholesterol and increase HDL-cholesterol concentrations.

10. Metabolic effects of progestogens
• The contraceptive effect of progestogens is related to suppression of
LH secretion (tending to suppress ovulation) and to effects on cervical
mucus that make it hostile to sperm, and on the endometrium that
reduces the likelihood of successful implantation
• Levonorgestrel, gestodene, norgestimate and desogestrel have
androgenic as wellas progestogenic activity, and tend to increase
plasma LDL-cholesterol and reduce HDL-cholesterol concentrations.

12. Effects of hormonal contraceptives on lipid metabolism
and risk of vascular disease
• The overall effect of combined oral contraceptives on lipid metabolism depends
on the type and dose of oestrogen and progestogen and on the presence of any
genetic tendency to hyperlipidaemia.
• In general, the effects of the oestrogen and progestogen tend to cancel each
other out, though most modern agents tend slightly to reduce plasma LDL-
cholesterol and increase HDL-cholesterol concentrations. They may also slightly
increase triglyceride concentrations.
• It is noteworthy that in women who do not smoke cigarettes and who are
normotensive, there is no evidence of an increase in the relative risk of
cardiovascular disease associated with long-term use of combined oral
contraceptives.
• Even in women who smoke or are hypertensive, the absolute risk, though higher,
remains very low.

13. • Contraindications to the use of the combined oral contraceptives
include a personal history of stroke, myocardial infarction or venous
thromboembolism, severe hypertension and heavy cigarette smoking.
• There is no evidence of increased risk of venous thrombosis,
cardiovascular or cerebrovascular disease in women using
progestogen-only contraceptives.

14. Effects of oral contraceptives on glucose
homoeostasis and diabetes
• Any adverse effect of oral contraceptives on glucose tolerance
appears to be related to the progestogen component.
• Progestogens antagonize the effects of insulin and increase the area
under the curve of insulin response to oral glucose tolerance tests,
but the effects on glucose tolerance, though statistically significant,
are not clinically so
• There is no need to avoid combined preparations in patients with
uncomplicated diabetes. Progestogen only oral contraceptives are
safe in patients with type 1 diabetes and can be recommended in
many patients for whom combined products are contraindicated

15. Hormone replacement therapy
• The primary aim of hormone replacement therapy in postmenopausal
women is usually to reduce the clinical features of oestrogen
deficiency, which include hot flushes, depression, vaginal dryness and
consequent dyspareunia.
• Particularly in women who undergo a premature menopause, a
secondary aim may be to reduce the risk of long-term consequences
of oestrogen deficiency, particularly osteoporosis.
• Although menopausal symptoms are caused by oestrogen deficiency,
oestrogen replacement should be accompanied by cyclical or
continuous progestogen replacement in order to prevent endometrial
hyperplasia

17. Metabolic effects of the menopause
• The onset of the menopause is accompanied by an increase in the
plasma concentrations of LDL-cholesterol and triglycerides; HDL
concentrations fall slightly
• These changes are all pro-atherogenic and are thought to be
important factors in the increase in the prevalence of cardiovascular
disease that occurs following the menopause

20. Metabolic effects of HRT
• The metabolic effects of HRT depend upon the steroids used, their
doses and the route of administration, but in summary, oestrogen
replacement tends to reduce LDL cholesterol concentrations.
• Oestrogens also increase the clearance of remnant particles and
reduce the concentration of lipoprotein(a). Although, when used
alone, oestrogen replacement may increase HDL concentration

21. Adverse consequences of hormone replacement
therapy
• The most important of these include a small but significant increased
in the risk of venous thromboembolism.
• There is no increase in the risk of endometrial cancer or ovarian
cancer.
• The risk of breast cancer does increase in women who use combined
HRT for more than five years, although only very slightly

22. Hormone replacement therapy and heart
disease
• Early epidemiological studies suggested that HRT reduces the risk of
coronary disease,meta-analyses of primary prevention trials suggest
that HRT confers either no, or only a very small, degree of protection
against cardiovascular death in younger women, and none in older
women.

23. Hormone replacement therapy and osteoporosis
• The increased rate of bone loss associated with oestrogen deficiency
is a major cause of morbidity and mortality in older women,this is
mainly due to the increased risk of hip fracture.
• Evidence from numerous trials is that HRT, whether with oestrogen
alone or combined oestrogen and progestogen, increases bone
mineral density and reduces the risk of hip fracture. However,
although significant, the effect is small, and, except in women who
sustain a premature menopause, HRT is not recommended solely for
the prevention of fractures.