1126 THE LANCET

age at the birth of the last child, 40-41 years, found inreligious communities who eschew contraception.5 The endof female fertility precedes menopause by 9-10 years .6 Atthat age, most women have seemingly normal and regularcycles with a biphasic basal body temperature pattern thatreflects progesterone production during the luteal phase.Generations of gynaecologists have taken such findings assufficient proof of normal female fertility.What about a uterine factor interfering with

implantation? The good results of in-vitro fertilisation inperimenopausal and postmenopausal women with oocytesfrom young donors suggest that oocyte quality rather thanuterine environment is the limiting factor.7 Theseobservations support the hypothesis that, at younger ages,selection of high-quality oocytes takes placed Oocytes ofprogressively inferior quality remain as the woman getsolder. Apart from the diminished probability of conceiving,this observation also explains the higher rate of abortions,congenital defects, and chromosomal aberrations amongolder women. The deterioration of oocyte quality goesunnoticed for years because the menstrual cycle remainsregular until about age 45.9 Only thereafter, when the folliclestore is almost depleted, does the menstrual pattern becomeerratic.

If the number of remaining follicles determines not onlythe age at menopause but also the reproductive age of awoman, what happens when medical interventions such asradiotherapy or gynaecological surgery suddenly reduce thenumber of follicles? Let us consider, for example, patientsundergoing a unilateral ovariectomy. This is a routine

operation for women who present with persisting ovariancysts. The gynaecologist can usually restore the ovary afterselective dissection of the cyst, but removal of ovary and cystin one lump is easier and much quicker. When theovariectomy is done below the age of 30, menopause will beadvanced by 7 years, according to the biphasic model ofFaddy et al.2 It is likely that the ages of subfertility anddefmite sterility will be advanced accordingly. If thosewomen also follow the growing trend of delayedchildbearing,lO their effective reproductive window maybecome almost closed.The predictions by Faddy and colleagues are supported

only by anecdotal evidence. Hundreds of thousands ofwomen have reached the menopause with one ovary, andthe absence of epidemiological evidence throws somedoubt on the validity of their model. More fundamentally, itreminds us that we should treat those little, mysteriousorgans that hold the origin of life with the greatest possiblerespect.

E. R. te Velde

1. Speroff L, Glas RH, Kase NG. Clinical gynecologic endocrinology andinfertility. 4th ed. Baltimore: Williams and Wilkins, 1989: 124.

2. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF.Accelerated disappearance of ovarian follicles in mid-life: implicationsfor forecasting menopause. Hum Reprod 1992; 7: 1342-46.

3. Leridon H. Human fertility: the basic components. Chicago: Universityof Chicago Press, 1977: 202.

4. Van Noord-Zaadstra BM, Looman CWN, Alsbach H, Habbema JDF,te Velde ER, Karbaat J. Delaying childbearing: effect of age on

fecundity and outcome of pregnancy. BMJ 1991; 302: 1361-65.5. Bongaarts J. The proximate determinants of natural marital fertility.

Center for Policy Studies. Working paper no 89. New York: PopulationCouncil, 1982: 1-43.

6. Stein ZA. A woman’s age: childbearing and child rearing. Am J Epidemiol1985; 121: 327-42.

7. Sauer MV, Paulson RJ, Lobo RA. Pregnancy after age 50: application ofoocyte donation to women after natural menopause. Lancet 1993; 341:321-23.

8. Henderson SA, Edwards RG. Chiasma frequency and maternal age inmammals. Nature 1968; 218: 22-28.

9. Treloar AE. Menstrual cyclicity and the premenopause. Maturitas 1981;3: 49-64.

10. Mosher WD, Pratt WF. Fecundity and infertility in the United States:incidence and trends. Fertil Steril 1991; 56: 192-93.

OLFACTION

In praise of stinks

Our senses are one of our main sources of pleasure. In thepast sensual pleasure was perceived as threatening our lifehereafter; today it is seen as threatening our life in the hereand now. Eating and drinking, sex, but not as yetdefaecation, are viewed as dangerous pastimes that shouldbe indulged in only as necessary and then in a "healthy"fashion. Are we now in danger of being denied the pleasuresof smell? Odour pollution seems set to become an expensivepublic health issue. As Shustennan1 has pointed out,so-called nasty smells are by no means the same thing asthreats to health.

Fanger in a series of articlesabout smell-free environments,introduces us to two new

units-the olf and the decipol.The decipol is defined as thepollution caused by one

standard person (1 olf)ventilated by 10 L/s of

unpolluted air, the underlyingassumptions being "steadystate conditions and completemixing". A sedentary personrates 1 olf, active peopleanything between 5 and 11 olfs,a smoker smoking 25 olfs, and asmoker not smoking 6 olfs.1The olf is not measurable byany instrument but isdetermined by a panel of judgeswho constitute collectively a

"man meter".

1 olf is the air pollutionfrom one standardperson-ie, from one

average adult workingin an office, sedentary,and in thermal comfortwith a hygienicstandard equivalent to07 bath/day. From ref2, with permission.

Compared with manymembers of the animal

kingdom our sense of smell ispoor and rudimentary. For

dogs the world is full of smellsthat make country walks a

constant and often rewardingadventure. Some smells are soattractive that one’s canine

companion finds it desirable toroll in a decaying rat so that the smell may be brought homeand enjoyed at leisure. However, our man meter so

disapproves of that particular smell that washing is a

prerequisite of admittance to the house.Our ability to smell may be rudimentary but is

nonetheless a source of sensual pleasure. Unfortunately, orsometimes fortunately, the sensation fatigues very quickly,so that after a few minutes all-pervasive odours are no longersensed. Smells are the most transient of our pleasures. Yetthey have an extraordinary power to evoke the past-nothing except smell can carry us so surely to other placesand other times. The smell of blackboard chalk coupled witha particular sort of floor polish recreates school far more

1127THE LANCET

powerfully than old photographs or verbal reminders. A hotdry summer day and the whiff of dung can immediatelytransport one to India.

Smell is of course allied to taste. Our appetite is createdby smells of anticipation, and a good dinner succeedsby offering us a wide variety so that our taste is

constantly exposed to new stimuli. So, should we sacrificesmell on the altar of atmospheric purity? After all,serious atmospheric threats to our health such as carbonmonoxide, asbestos, and radon are odourless. And

speaking personally, I like "people smell". The smell ofyoung babies and of small children, the smell of some menand many women (if not drowned in cheap scent). Amongthe worst smells are the artificial odours that are pumpedinto the air to overpower the wholesome smells of farts and

faeces, of sweat and stout. Even the stink of silage and pigslurry are short lived in their effect and are part of the richworld of smell. There is also a question of pheromones.Would Fanger and his disciples deny me the subliminalexcitement to which I may all unwittingly be exposed in mydealings with the opposite, and for all I know, the samesex?

In fairness, Fanger’s concern is not with the greatoutdoors but the indoor office environment. I doubtwhether he would deny us delicious smells such as oldfashioned roses, hyacinths, new-mown hay, linseed oil, anew tennis and an old cricket ball, wet dogs and wet tweeds,salt marshes and sea. Smells are sensual and like all sensual

experience a cause of intense pleasure and occasional pain.To my mind smells are not pollution. May we be preservedfrom those who wish to sanitise our environment on thebasis of man meters.

James McCormick

1. Shusterman D. Community health and odor pollution regulation. Am JPubl Health 1992; 82: 1566-67.

2. Fanger PO. Perceived quality of indoor and ambient air. Proceedings ofthe Indoor Ambient Air Quality Conference, London, 1988: 365-76.

DERMATOLOGY

Epidemic black spots on the scalp

All public health physicians know that clusters of anunusual disease in a small area can generate communal

anxiety quite out of proportion to the morbidity of thediseased All the more so with a new condition that affects

many children, and when the cause is unknown. Thissituation arose over a ten-year period in certain townships inthe Rocky Mountain states in the USA, where epidemics ofblack spots developed on the scalps of schoolchildren.Several communities were affected, and in the largestepidemic 1380 cases were recorded. The lesions were blackor brown macules, 1-5 mm in diameter. Those affected hadfrom 1 to 20 spots on the scalp, but nowhere else, and theywere otherwise well. Suggested diagnoses included tineanigra, macula cerulea (due to flea bites), naevi, and "dirt",but confirmation was lacking despite examination of skinbiopsy specimens (no abnormalities seen).

In the latest epidemic in Green River, Wyoming, in 1989,only one school of nine in the district reported cases andparents were advised by the local health authority to keeptheir children at home when they had the spots. Parentalpressure prompted pigmentary probing.2 The Wyoming

Department of Health duly found that 40% of children atthe school had the black spots, but siblings at other schoolshad no spots. When children graduated to the middleschool, in a different building, they lost their spots. Scalpscrapings from the spots were analysed by gas-liquidchromatography and infrared spectroscopy and the pigmentproved to be a complex mixture of long-chain hydrocarbonsresembling tar.The school roof was in poor repair, with large exposed

patches of torn tar-paper. Small black flakes eddied in thedusty wind in the playground. Chromatographic analysis ofthe roof tar and the black dust showed that they wereidentical to the tar spots on the scalps. In the best traditionsof Koch, tar-dust was sprinkled on the scalp of an

investigator, who then exercised vigorously. Particles

trapped by the hair dissolved in the skin lipid and sweat tostain the scalp and reproduce the "disease".But why are black scalp spots apparently confined to

certain mountainous states in the western USA? As with so

many other epidemic diseases, climatic factors provide anexplanation. In areas with little rain, roof repairs are

infrequent. High-altitude ultraviolet radiation degrades theexposed tar, and the strong and consistent winter winds ofthe Wyoming wind corridor then disperse the aetiologicalagent in the community.

John L. Burton

1. Spitzer WO, Dales R, Schechter MT, Tousignant P, Hutcheon M.Subjective fears and objective data: an epidemiologic study ofenvironmental health concerns. Trans Assoc Am Phys 1987; 100: 40-41.

2. Cobb N, Etzel Ruth A, Hudson R. Black spots on the scalps ofschoolchildren: a recurrent condition in the windy West. WesternMed J 1993; 158: 139-41.

BLEEDING DISORDERS

Haemophilia B and factor IX mutations

Haemophilia B or Christmas disease is an X-linkedrecessive disorder caused by mutations of the gene encodingcoagulation factor IX, a 415 aminoacid glycoprotein.Clinically the disorder ranges from the severe form, withabsent factor IX coagulant activity accompanied byrecurrent spontaneous haemarthroses, to a mild variety,with excessive bleeding only after surgery. 1 The

heterogeneous nature of this disease reflects the vast array ofcausal mutations in the factor IX gene, most of which affectthe aminoacid sequence of the protein.2 A few of thedescribed mutations result in normal factor IX proteinstructure but abnormally low levels of expression.Haemophilia B-Leyden is one such rare variant. Firstidentified in a Dutch family, the disease is characterised bysevere haemophilia during childhood which improves to amild symptomless condition after puberty.3 Plasma factorIX concentrations in such patients increase from low orundetectable ( < 1 % of normal) to around 50% after

puberty. Twelve such mutations have been identified ascausing haemophilia B-Leyden, all localised to the promoterregion (nucleotides - 20, - 6, - 5, + 8, and + 13 relative tothe start site of transcription) of the factor IX gene.2 Crossleyet al4 lately described another Leyden-like mutation (G to Cat position - 26) within this promoter region; however, thispatient (haemophilia B-Brandenburg) showed no clinicalimprovement after puberty.